Cardiology

Models using novel kidney and cardiac biomarkers were the most effective predictors of 10-year risk for atherosclerotic cardiovascular disease in chronic kidney disease patients, in a new study.

Chronic kidney disease (CKD) patients may be at increased risk for atherosclerotic cardiovascular disease, but no ASCVD risk prediction models are currently in place to inform clinical care and prevention strategies, Joshua Bundy, PhD, of Tulane University, New Orleans, and colleagues wrote in their paper, published in the Journal of the American Society of Nephrology.

To improve the accuracy of ASCVD risk prediction, the researchers developed several models using data from the Chronic Renal Insufficiency Cohort (CRIC) study. This longitudinal cohort study included more than 2,500 adult CKD patients. The participants’ ages ranged from 21-74 years, with the mean age having been 55.8 years, and 52.0% of the cohort was male.

Kidney function was defined using the glomerular filtration rate; the mean estimated glomerular filtration rate (eGFR) of the study participants was 56.0 mL/min per 1.73m². The primary endpoint for the prediction models was incident ASCVD, defined as a composite of incident fatal or nonfatal stroke or MI.

A total of 252 incident ASCVD events occurred during the first 10 years of follow-up from baseline (1.9 events per 1,000 person-years). Patients with ASCVD events were more likely to be older, Black, and current smokers. They also were more likely than those who did not experience ASCVD events to have less than a college level education, to have a history of diabetes, and to use blood pressure–lowering medications.

“In our study, we created two new prediction tools for patients with CKD: the first is a simple model that includes factors routinely measured by health care providers and the second is an expanded model with additional variables particularly important to patients with CKD, including measures of long-term blood sugar, inflammation, and kidney and heart injury,” he explained. “We found that the new models are better able to classify patients who will or will not have a stroke or heart attack within 10 years, compared with the standard models. The new tools may better assist health care providers and patients with CKD in shared decision-making for prevention of heart disease.”
 

Results

The area under the curve for a prediction model using coefficients estimated within the CRIC sample was 0.736. This represented an accuracy higher than the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), which have shown an AUC of 0.730 (P = .03). The PCE were developed by the ACC and the AHA in 2013 to estimate ASCVD risk in the primary prevention population.

The second CRIC model that was developed using clinically available variables had an AUC of 0.760. However, the third CRIC biomarker-enriched model was even more effective, with an AUC of 0.771 – significantly higher than the clinical model (P = .001).

Model 1 included the ACC/AHA PCE variables with coefficients recalculated in the CRIC study sample. Model 2 (the CRIC Clinical Model) included age, HDL cholesterol, systolic BP, current smoking, urinary albumin-to-creatinine ratio (ACR), hemoglobin A1c, and hemoglobin. Model 3 (the CRIC Enriched Model) included age, total cholesterol, HDL cholesterol, current smoking, urinary ACR, A1c, apolipoprotein B, high-sensitivity C-reactive protein (hsCRP), troponin T, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP).

Both the clinical and biomarker models improved reclassification of non-ASCVD events, compared with the PCEs (6.6% and 10.0%, respectively).

Several factors not included in prior prediction models were important for atherosclerotic CVD prediction among patients with CKD, the researchers noted. These included variables routinely measured in clinical practice as well as biomarkers: measures of long-term glycemia (A1c), inflammation (hsCRP), kidney injury (urinary ACR), and cardiac injury (troponin T and NT-proBNP).

Patients who had an ASCVD event had higher levels of A1c, systolic and diastolic BP, urinary ACR, troponin T, and NT-proBNP; these patients also had lower levels of HDL cholesterol, eGFR, and hemoglobin, compared with those who did not have an event.

The study findings were limited by several factors including the selection of study participants based on a single assessment of kidney function, who had an above average baseline ASCVD risk, the researchers noted. Other limitations included the inability to include imaging variables in the models, and the overestimated risk in the highest predicted probability groups in the CRIC study.

However, the models significantly improve prediction beyond the ACC/AHA PCE in patients with CKD, they concluded.

 

Models may inform shared decision-making

The development of new prediction models is important, because cardiovascular disease is the leading cause of death among U.S. adults and preventing CVD is a major public health challenge, lead author Dr. Bundy said in an interview.

“In an effort to prevent CVD, risk prediction equations can help identify patients who are at high risk for developing CVD and who may benefit from initiation or intensification of preventive and/or therapeutic measures. Simultaneously, chronic kidney disease is prevalent and those with CKD are often considered at high risk for CVD,” he said.

“However, common risk prediction tools were developed for the general population and may not work as well in patients with CKD, who may have different risk factors. Improving risk prediction in patients with CKD may help identify those among this growing population who are truly at high risk, as well as identify those who are at low risk and less likely to benefit from invasive procedures,” Dr. Bundy explained.
 

Glomerular filtration rate was not a strong predictor of atherosclerotic CVD

“One of the surprising findings was that estimated glomerular filtration rate was not a strong predictor and was not included in our final models,” Dr. Bundy said.

“We know that eGFR is a very important measurement in this population, but our results suggest that, at least in our sample, urinary albumin-to-creatinine ratio and cardiac biomarkers like troponin T and NT-proBNP are stronger predictors of atherosclerotic CVD in a population with reduced kidney function,” he said.

“Patient characteristics like age, blood pressure, and cholesterol are used by health care providers to predict whether a person will have a heart attack or stroke. However, most currently available prediction tools were not made for use in patients with CKD, which is a condition that is becoming more common and is likely to be seen by more health care providers in family practice,” said Dr. Bundy. “These people with CKD may have different risk factors for heart disease.”
 

Models are useful for clinical practice

“We are seeing rising numbers of patients with CKD in the population because of increasing age, rising rates of diabetes, and hypertension,” Noel Deep, MD, said in an interview. “The current practice of medicine does not have CKD-specific prediction models for ASCVD development, and current risks are calculated based on prediction models developed for the general population.”

Courtesy Dr. Noel Deep

“Having a prediction model that incorporates criteria/variables associated with CKD improves our ability to accurately identify and address the risk of ASCVD in this particular patient population,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.

“We always knew that CKD does place the individual at higher risk for developing ASCVD, but I was impressed by the significant improvement in the prediction models using CKD specific tools, such as cardiac biomarkers (NT-proBNP), intensity of diabetes control (A1c), tobacco use, urinary albuminuria, in addition to advancing age,” he said. “Many of the laboratory tests listed in this study are commonly available and can be easily incorporated into our evaluation for and management of ASCVD in our patients with CKD.”

“As a practicing primary care physician, I would say that this study emphasizes the importance of identifying and working toward mitigating the associated health risks that our patients with CKD might have coexisting and that significantly contribute to progression of CKD,” said Dr. Deep, who is also assistant clinical professor at the Medical College of Wisconsin, Wausau. “By addressing these risk factors, we can positively impact the health of our patients with CKD and decrease the morbidity and mortality, and health care costs. These predictive models can hopefully help us more accurately identify the risk of ASCVD thereby decreasing unnecessary diagnostic procedures and interventions which carry their own risks and morbidity.”

Looking ahead, “these predictive models should be assessed and validated in large studies in diverse populations and those with different risk factors for ASCVD because CKD can be caused by several different medical conditions each with potential to contribute to ASCVD,” Dr. Deep added.
 

Limitations and next steps

“Although we externally validated our models in two population-based cohort studies, the individuals in these datasets were selected based on only one assessment of kidney function,” Dr. Bundy noted. “Furthermore, the best practices for implementing risk prediction models in the clinic remain to be determined, especially as new models are developed.

“While our models show promising performance for predicting 10-year risk of atherosclerotic CVD, more clinical trials are needed to test implementation of these models for improving patient care and disease prevention.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support came from the University of Pennsylvania Clinical and Translational Science Award, Johns Hopkins University, the University of Maryland, Clinical and Translational Science Collaborative of Cleveland, the National Center for Advancing Translational Sciences component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research, University of Illinois at Chicago, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Kaiser Permanente, and the University of New Mexico. Lead author Dr. Bundy was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

This article was updated on 2/17/2021.

Models using novel kidney and cardiac biomarkers were the most effective predictors of 10-year risk for atherosclerotic cardiovascular disease in chronic kidney disease patients, in a new study.

Chronic kidney disease (CKD) patients may be at increased risk for atherosclerotic cardiovascular disease, but no ASCVD risk prediction models are currently in place to inform clinical care and prevention strategies, Joshua Bundy, PhD, of Tulane University, New Orleans, and colleagues wrote in their paper, published in the Journal of the American Society of Nephrology.

To improve the accuracy of ASCVD risk prediction, the researchers developed several models using data from the Chronic Renal Insufficiency Cohort (CRIC) study. This longitudinal cohort study included more than 2,500 adult CKD patients. The participants’ ages ranged from 21-74 years, with the mean age having been 55.8 years, and 52.0% of the cohort was male.

Kidney function was defined using the glomerular filtration rate; the mean estimated glomerular filtration rate (eGFR) of the study participants was 56.0 mL/min per 1.73m². The primary endpoint for the prediction models was incident ASCVD, defined as a composite of incident fatal or nonfatal stroke or MI.

A total of 252 incident ASCVD events occurred during the first 10 years of follow-up from baseline (1.9 events per 1,000 person-years). Patients with ASCVD events were more likely to be older, Black, and current smokers. They also were more likely than those who did not experience ASCVD events to have less than a college level education, to have a history of diabetes, and to use blood pressure–lowering medications.

“In our study, we created two new prediction tools for patients with CKD: the first is a simple model that includes factors routinely measured by health care providers and the second is an expanded model with additional variables particularly important to patients with CKD, including measures of long-term blood sugar, inflammation, and kidney and heart injury,” he explained. “We found that the new models are better able to classify patients who will or will not have a stroke or heart attack within 10 years, compared with the standard models. The new tools may better assist health care providers and patients with CKD in shared decision-making for prevention of heart disease.”
 

Results

The area under the curve for a prediction model using coefficients estimated within the CRIC sample was 0.736. This represented an accuracy higher than the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), which have shown an AUC of 0.730 (P = .03). The PCE were developed by the ACC and the AHA in 2013 to estimate ASCVD risk in the primary prevention population.

The second CRIC model that was developed using clinically available variables had an AUC of 0.760. However, the third CRIC biomarker-enriched model was even more effective, with an AUC of 0.771 – significantly higher than the clinical model (P = .001).

Model 1 included the ACC/AHA PCE variables with coefficients recalculated in the CRIC study sample. Model 2 (the CRIC Clinical Model) included age, HDL cholesterol, systolic BP, current smoking, urinary albumin-to-creatinine ratio (ACR), hemoglobin A1c, and hemoglobin. Model 3 (the CRIC Enriched Model) included age, total cholesterol, HDL cholesterol, current smoking, urinary ACR, A1c, apolipoprotein B, high-sensitivity C-reactive protein (hsCRP), troponin T, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP).

Both the clinical and biomarker models improved reclassification of non-ASCVD events, compared with the PCEs (6.6% and 10.0%, respectively).

Several factors not included in prior prediction models were important for atherosclerotic CVD prediction among patients with CKD, the researchers noted. These included variables routinely measured in clinical practice as well as biomarkers: measures of long-term glycemia (A1c), inflammation (hsCRP), kidney injury (urinary ACR), and cardiac injury (troponin T and NT-proBNP).

Patients who had an ASCVD event had higher levels of A1c, systolic and diastolic BP, urinary ACR, troponin T, and NT-proBNP; these patients also had lower levels of HDL cholesterol, eGFR, and hemoglobin, compared with those who did not have an event.

The study findings were limited by several factors including the selection of study participants based on a single assessment of kidney function, who had an above average baseline ASCVD risk, the researchers noted. Other limitations included the inability to include imaging variables in the models, and the overestimated risk in the highest predicted probability groups in the CRIC study.

However, the models significantly improve prediction beyond the ACC/AHA PCE in patients with CKD, they concluded.

 

Models may inform shared decision-making

The development of new prediction models is important, because cardiovascular disease is the leading cause of death among U.S. adults and preventing CVD is a major public health challenge, lead author Dr. Bundy said in an interview.

“In an effort to prevent CVD, risk prediction equations can help identify patients who are at high risk for developing CVD and who may benefit from initiation or intensification of preventive and/or therapeutic measures. Simultaneously, chronic kidney disease is prevalent and those with CKD are often considered at high risk for CVD,” he said.

“However, common risk prediction tools were developed for the general population and may not work as well in patients with CKD, who may have different risk factors. Improving risk prediction in patients with CKD may help identify those among this growing population who are truly at high risk, as well as identify those who are at low risk and less likely to benefit from invasive procedures,” Dr. Bundy explained.
 

Glomerular filtration rate was not a strong predictor of atherosclerotic CVD

“One of the surprising findings was that estimated glomerular filtration rate was not a strong predictor and was not included in our final models,” Dr. Bundy said.

“We know that eGFR is a very important measurement in this population, but our results suggest that, at least in our sample, urinary albumin-to-creatinine ratio and cardiac biomarkers like troponin T and NT-proBNP are stronger predictors of atherosclerotic CVD in a population with reduced kidney function,” he said.

“Patient characteristics like age, blood pressure, and cholesterol are used by health care providers to predict whether a person will have a heart attack or stroke. However, most currently available prediction tools were not made for use in patients with CKD, which is a condition that is becoming more common and is likely to be seen by more health care providers in family practice,” said Dr. Bundy. “These people with CKD may have different risk factors for heart disease.”
 

Models are useful for clinical practice

“We are seeing rising numbers of patients with CKD in the population because of increasing age, rising rates of diabetes, and hypertension,” Noel Deep, MD, said in an interview. “The current practice of medicine does not have CKD-specific prediction models for ASCVD development, and current risks are calculated based on prediction models developed for the general population.”

Courtesy Dr. Noel Deep

“Having a prediction model that incorporates criteria/variables associated with CKD improves our ability to accurately identify and address the risk of ASCVD in this particular patient population,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.

“We always knew that CKD does place the individual at higher risk for developing ASCVD, but I was impressed by the significant improvement in the prediction models using CKD specific tools, such as cardiac biomarkers (NT-proBNP), intensity of diabetes control (A1c), tobacco use, urinary albuminuria, in addition to advancing age,” he said. “Many of the laboratory tests listed in this study are commonly available and can be easily incorporated into our evaluation for and management of ASCVD in our patients with CKD.”

“As a practicing primary care physician, I would say that this study emphasizes the importance of identifying and working toward mitigating the associated health risks that our patients with CKD might have coexisting and that significantly contribute to progression of CKD,” said Dr. Deep, who is also assistant clinical professor at the Medical College of Wisconsin, Wausau. “By addressing these risk factors, we can positively impact the health of our patients with CKD and decrease the morbidity and mortality, and health care costs. These predictive models can hopefully help us more accurately identify the risk of ASCVD thereby decreasing unnecessary diagnostic procedures and interventions which carry their own risks and morbidity.”

Looking ahead, “these predictive models should be assessed and validated in large studies in diverse populations and those with different risk factors for ASCVD because CKD can be caused by several different medical conditions each with potential to contribute to ASCVD,” Dr. Deep added.
 

Limitations and next steps

“Although we externally validated our models in two population-based cohort studies, the individuals in these datasets were selected based on only one assessment of kidney function,” Dr. Bundy noted. “Furthermore, the best practices for implementing risk prediction models in the clinic remain to be determined, especially as new models are developed.

“While our models show promising performance for predicting 10-year risk of atherosclerotic CVD, more clinical trials are needed to test implementation of these models for improving patient care and disease prevention.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support came from the University of Pennsylvania Clinical and Translational Science Award, Johns Hopkins University, the University of Maryland, Clinical and Translational Science Collaborative of Cleveland, the National Center for Advancing Translational Sciences component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research, University of Illinois at Chicago, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Kaiser Permanente, and the University of New Mexico. Lead author Dr. Bundy was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

This article was updated on 2/17/2021.

Models using novel kidney and cardiac biomarkers were the most effective predictors of 10-year risk for atherosclerotic cardiovascular disease in chronic kidney disease patients, in a new study.

Chronic kidney disease (CKD) patients may be at increased risk for atherosclerotic cardiovascular disease, but no ASCVD risk prediction models are currently in place to inform clinical care and prevention strategies, Joshua Bundy, PhD, of Tulane University, New Orleans, and colleagues wrote in their paper, published in the Journal of the American Society of Nephrology.

To improve the accuracy of ASCVD risk prediction, the researchers developed several models using data from the Chronic Renal Insufficiency Cohort (CRIC) study. This longitudinal cohort study included more than 2,500 adult CKD patients. The participants’ ages ranged from 21-74 years, with the mean age having been 55.8 years, and 52.0% of the cohort was male.

Kidney function was defined using the glomerular filtration rate; the mean estimated glomerular filtration rate (eGFR) of the study participants was 56.0 mL/min per 1.73m². The primary endpoint for the prediction models was incident ASCVD, defined as a composite of incident fatal or nonfatal stroke or MI.

A total of 252 incident ASCVD events occurred during the first 10 years of follow-up from baseline (1.9 events per 1,000 person-years). Patients with ASCVD events were more likely to be older, Black, and current smokers. They also were more likely than those who did not experience ASCVD events to have less than a college level education, to have a history of diabetes, and to use blood pressure–lowering medications.

“In our study, we created two new prediction tools for patients with CKD: the first is a simple model that includes factors routinely measured by health care providers and the second is an expanded model with additional variables particularly important to patients with CKD, including measures of long-term blood sugar, inflammation, and kidney and heart injury,” he explained. “We found that the new models are better able to classify patients who will or will not have a stroke or heart attack within 10 years, compared with the standard models. The new tools may better assist health care providers and patients with CKD in shared decision-making for prevention of heart disease.”
 

Results

The area under the curve for a prediction model using coefficients estimated within the CRIC sample was 0.736. This represented an accuracy higher than the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), which have shown an AUC of 0.730 (P = .03). The PCE were developed by the ACC and the AHA in 2013 to estimate ASCVD risk in the primary prevention population.

The second CRIC model that was developed using clinically available variables had an AUC of 0.760. However, the third CRIC biomarker-enriched model was even more effective, with an AUC of 0.771 – significantly higher than the clinical model (P = .001).

Model 1 included the ACC/AHA PCE variables with coefficients recalculated in the CRIC study sample. Model 2 (the CRIC Clinical Model) included age, HDL cholesterol, systolic BP, current smoking, urinary albumin-to-creatinine ratio (ACR), hemoglobin A1c, and hemoglobin. Model 3 (the CRIC Enriched Model) included age, total cholesterol, HDL cholesterol, current smoking, urinary ACR, A1c, apolipoprotein B, high-sensitivity C-reactive protein (hsCRP), troponin T, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP).

Both the clinical and biomarker models improved reclassification of non-ASCVD events, compared with the PCEs (6.6% and 10.0%, respectively).

Several factors not included in prior prediction models were important for atherosclerotic CVD prediction among patients with CKD, the researchers noted. These included variables routinely measured in clinical practice as well as biomarkers: measures of long-term glycemia (A1c), inflammation (hsCRP), kidney injury (urinary ACR), and cardiac injury (troponin T and NT-proBNP).

Patients who had an ASCVD event had higher levels of A1c, systolic and diastolic BP, urinary ACR, troponin T, and NT-proBNP; these patients also had lower levels of HDL cholesterol, eGFR, and hemoglobin, compared with those who did not have an event.

The study findings were limited by several factors including the selection of study participants based on a single assessment of kidney function, who had an above average baseline ASCVD risk, the researchers noted. Other limitations included the inability to include imaging variables in the models, and the overestimated risk in the highest predicted probability groups in the CRIC study.

However, the models significantly improve prediction beyond the ACC/AHA PCE in patients with CKD, they concluded.

 

Models may inform shared decision-making

The development of new prediction models is important, because cardiovascular disease is the leading cause of death among U.S. adults and preventing CVD is a major public health challenge, lead author Dr. Bundy said in an interview.

“In an effort to prevent CVD, risk prediction equations can help identify patients who are at high risk for developing CVD and who may benefit from initiation or intensification of preventive and/or therapeutic measures. Simultaneously, chronic kidney disease is prevalent and those with CKD are often considered at high risk for CVD,” he said.

“However, common risk prediction tools were developed for the general population and may not work as well in patients with CKD, who may have different risk factors. Improving risk prediction in patients with CKD may help identify those among this growing population who are truly at high risk, as well as identify those who are at low risk and less likely to benefit from invasive procedures,” Dr. Bundy explained.
 

Glomerular filtration rate was not a strong predictor of atherosclerotic CVD

“One of the surprising findings was that estimated glomerular filtration rate was not a strong predictor and was not included in our final models,” Dr. Bundy said.

“We know that eGFR is a very important measurement in this population, but our results suggest that, at least in our sample, urinary albumin-to-creatinine ratio and cardiac biomarkers like troponin T and NT-proBNP are stronger predictors of atherosclerotic CVD in a population with reduced kidney function,” he said.

“Patient characteristics like age, blood pressure, and cholesterol are used by health care providers to predict whether a person will have a heart attack or stroke. However, most currently available prediction tools were not made for use in patients with CKD, which is a condition that is becoming more common and is likely to be seen by more health care providers in family practice,” said Dr. Bundy. “These people with CKD may have different risk factors for heart disease.”
 

Models are useful for clinical practice

“We are seeing rising numbers of patients with CKD in the population because of increasing age, rising rates of diabetes, and hypertension,” Noel Deep, MD, said in an interview. “The current practice of medicine does not have CKD-specific prediction models for ASCVD development, and current risks are calculated based on prediction models developed for the general population.”

Courtesy Dr. Noel Deep

“Having a prediction model that incorporates criteria/variables associated with CKD improves our ability to accurately identify and address the risk of ASCVD in this particular patient population,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.

“We always knew that CKD does place the individual at higher risk for developing ASCVD, but I was impressed by the significant improvement in the prediction models using CKD specific tools, such as cardiac biomarkers (NT-proBNP), intensity of diabetes control (A1c), tobacco use, urinary albuminuria, in addition to advancing age,” he said. “Many of the laboratory tests listed in this study are commonly available and can be easily incorporated into our evaluation for and management of ASCVD in our patients with CKD.”

“As a practicing primary care physician, I would say that this study emphasizes the importance of identifying and working toward mitigating the associated health risks that our patients with CKD might have coexisting and that significantly contribute to progression of CKD,” said Dr. Deep, who is also assistant clinical professor at the Medical College of Wisconsin, Wausau. “By addressing these risk factors, we can positively impact the health of our patients with CKD and decrease the morbidity and mortality, and health care costs. These predictive models can hopefully help us more accurately identify the risk of ASCVD thereby decreasing unnecessary diagnostic procedures and interventions which carry their own risks and morbidity.”

Looking ahead, “these predictive models should be assessed and validated in large studies in diverse populations and those with different risk factors for ASCVD because CKD can be caused by several different medical conditions each with potential to contribute to ASCVD,” Dr. Deep added.
 

Limitations and next steps

“Although we externally validated our models in two population-based cohort studies, the individuals in these datasets were selected based on only one assessment of kidney function,” Dr. Bundy noted. “Furthermore, the best practices for implementing risk prediction models in the clinic remain to be determined, especially as new models are developed.

“While our models show promising performance for predicting 10-year risk of atherosclerotic CVD, more clinical trials are needed to test implementation of these models for improving patient care and disease prevention.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support came from the University of Pennsylvania Clinical and Translational Science Award, Johns Hopkins University, the University of Maryland, Clinical and Translational Science Collaborative of Cleveland, the National Center for Advancing Translational Sciences component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research, University of Illinois at Chicago, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Kaiser Permanente, and the University of New Mexico. Lead author Dr. Bundy was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

This article was updated on 2/17/2021.

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

A version of this article first appeared on Medscape.com.

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

A version of this article first appeared on Medscape.com.

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

A version of this article first appeared on Medscape.com.

Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.

A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.

Bruce Jancin/MDedge News

Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).

“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.

The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”

The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”

All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.

Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.

The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.

The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
 

Guidelines upside down?

In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.

“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.

In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.

“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.

“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”

In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
 

Not all strategies are ‘created equal’

The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).

Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.

He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.

The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.

“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”

Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.

“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”

As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”

Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.

A version of this article first appeared on Medscape.com.

Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.

A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.

Bruce Jancin/MDedge News

Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).

“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.

The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”

The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”

All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.

Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.

The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.

The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
 

Guidelines upside down?

In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.

“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.

In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.

“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.

“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”

In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
 

Not all strategies are ‘created equal’

The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).

Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.

He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.

The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.

“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”

Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.

“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”

As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”

Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.

A version of this article first appeared on Medscape.com.

Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.

A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.

Bruce Jancin/MDedge News

Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).

“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.

The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”

The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”

All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.

Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.

The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.

The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
 

Guidelines upside down?

In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.

“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.

In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.

“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.

“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”

In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
 

Not all strategies are ‘created equal’

The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).

Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.

He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.

The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.

“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”

Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.

“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”

As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”

Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.

A version of this article first appeared on Medscape.com.

The Society for Cardiovascular Angiography and Interventions (SCAI) has refined its cardiogenic shock (CS) classification system based on the literature and clinician feedback from real-world experience.

Mitchel L. Zoler/MDedge News

“In the 2 years since publication in 2019, the initial definition has been broadly accepted and eagerly appreciated, allowing a very intuitive way to stage these patients for better communication, triage, and treatment,” Srihari S. Naidu, MD, professor of medicine, New York Medical College, Valhalla, said in an interview.

“But the initial definition was based on consensus opinion, with a lack of real fundamental data on segregating patients into different stages. Now we have a lot more data utilizing the definition, and it became very clear that there were a couple of limitations in the initial definition,” Dr. Naidu explained.

The refined CS classification system – authored by Dr. Naidu and a multidisciplinary panel of experts from specialties that included cardiac critical care, interventional cardiology, surgery, nursing, emergency medicine, and heart failure – was published online Jan. 31 in the Journal of the Society for Cardiovascular Angiography and Interventions, with simultaneous publication in the Journal of the American College of Cardiology.  

It maintains the five-stage pyramid of CS, starting with “at risk” and moving through “beginning,” “classic,” “deteriorating,” and “extremis” but now includes gradations of severity within each stage and pathways by which patients progress or recover.

“Progression across the SCAI shock stage continuum is a dynamic process, incorporating new information as available, and patient trajectories are important both for communication among clinicians and for decisionmaking regarding the next level of care and therapeutics,” the panel writes.

The second iteration adds a streamlined table incorporating commonly seen variables, based on lessons learned from validation studies and clinician experience.

“While keeping the same initial framework of looking at the three components of staging – the physical exam, the biochemical markers, and hemodynamics – we’ve made it very clear that there are some factors in each of these that are most typically seen. And then there are other factors that are consistent with that stage but don’t necessarily have to be seen, ... are not typically seen in that stage, or [are] not always present at that stage,” Dr. Naidu told this news organization.

The refined CS classification system provides more granularity on cardiac arrest as a risk modifier, which now excludes very brief episodes with rapid response to defibrillation and comprises only those patients who have impaired mental status with unknown neurologic recovery status after cardiopulmonary resuscitation.

Lactate level and thresholds have been highlighted to detect hypoperfusion but may be dissociated from hemodynamics in cases such as chronic heart failure.

In addition, patients may have other manifestations of end-organ hypoperfusion with a normal lactate level, and there are also important causes of an elevated lactate level other than shock.

The revision proposes a three-axis model of CS evaluation and prognostication that integrates shock severity, clinical phenotype, and risk modifiers as distinct elements that should be applied to individualize patient management.

The revision also places more emphasis on the trajectory of the patient with CS through hospitalization, including a “hub and spoke” model for transfer of higher-risk patients, including those with a deteriorating SCAI shock stage.

“It is our desire and belief that the revised SCAI SHOCK stage classification system will enhance both clinical care and CS research trial design,” the panel writes.

This statement has been endorsed by the American College of Cardiology, American College of Emergency Physicians, American Heart Association, European Society of Cardiology Association for Acute Cardiovascular Care, International Society for Heart and Lung Transplantation, Society of Critical Care Medicine, and Society of Thoracic Surgeons.

This research had no commercial funding. Dr. Naidu has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

The Society for Cardiovascular Angiography and Interventions (SCAI) has refined its cardiogenic shock (CS) classification system based on the literature and clinician feedback from real-world experience.

Mitchel L. Zoler/MDedge News

“In the 2 years since publication in 2019, the initial definition has been broadly accepted and eagerly appreciated, allowing a very intuitive way to stage these patients for better communication, triage, and treatment,” Srihari S. Naidu, MD, professor of medicine, New York Medical College, Valhalla, said in an interview.

“But the initial definition was based on consensus opinion, with a lack of real fundamental data on segregating patients into different stages. Now we have a lot more data utilizing the definition, and it became very clear that there were a couple of limitations in the initial definition,” Dr. Naidu explained.

The refined CS classification system – authored by Dr. Naidu and a multidisciplinary panel of experts from specialties that included cardiac critical care, interventional cardiology, surgery, nursing, emergency medicine, and heart failure – was published online Jan. 31 in the Journal of the Society for Cardiovascular Angiography and Interventions, with simultaneous publication in the Journal of the American College of Cardiology.  

It maintains the five-stage pyramid of CS, starting with “at risk” and moving through “beginning,” “classic,” “deteriorating,” and “extremis” but now includes gradations of severity within each stage and pathways by which patients progress or recover.

“Progression across the SCAI shock stage continuum is a dynamic process, incorporating new information as available, and patient trajectories are important both for communication among clinicians and for decisionmaking regarding the next level of care and therapeutics,” the panel writes.

The second iteration adds a streamlined table incorporating commonly seen variables, based on lessons learned from validation studies and clinician experience.

“While keeping the same initial framework of looking at the three components of staging – the physical exam, the biochemical markers, and hemodynamics – we’ve made it very clear that there are some factors in each of these that are most typically seen. And then there are other factors that are consistent with that stage but don’t necessarily have to be seen, ... are not typically seen in that stage, or [are] not always present at that stage,” Dr. Naidu told this news organization.

The refined CS classification system provides more granularity on cardiac arrest as a risk modifier, which now excludes very brief episodes with rapid response to defibrillation and comprises only those patients who have impaired mental status with unknown neurologic recovery status after cardiopulmonary resuscitation.

Lactate level and thresholds have been highlighted to detect hypoperfusion but may be dissociated from hemodynamics in cases such as chronic heart failure.

In addition, patients may have other manifestations of end-organ hypoperfusion with a normal lactate level, and there are also important causes of an elevated lactate level other than shock.

The revision proposes a three-axis model of CS evaluation and prognostication that integrates shock severity, clinical phenotype, and risk modifiers as distinct elements that should be applied to individualize patient management.

The revision also places more emphasis on the trajectory of the patient with CS through hospitalization, including a “hub and spoke” model for transfer of higher-risk patients, including those with a deteriorating SCAI shock stage.

“It is our desire and belief that the revised SCAI SHOCK stage classification system will enhance both clinical care and CS research trial design,” the panel writes.

This statement has been endorsed by the American College of Cardiology, American College of Emergency Physicians, American Heart Association, European Society of Cardiology Association for Acute Cardiovascular Care, International Society for Heart and Lung Transplantation, Society of Critical Care Medicine, and Society of Thoracic Surgeons.

This research had no commercial funding. Dr. Naidu has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

The Society for Cardiovascular Angiography and Interventions (SCAI) has refined its cardiogenic shock (CS) classification system based on the literature and clinician feedback from real-world experience.

Mitchel L. Zoler/MDedge News

“In the 2 years since publication in 2019, the initial definition has been broadly accepted and eagerly appreciated, allowing a very intuitive way to stage these patients for better communication, triage, and treatment,” Srihari S. Naidu, MD, professor of medicine, New York Medical College, Valhalla, said in an interview.

“But the initial definition was based on consensus opinion, with a lack of real fundamental data on segregating patients into different stages. Now we have a lot more data utilizing the definition, and it became very clear that there were a couple of limitations in the initial definition,” Dr. Naidu explained.

The refined CS classification system – authored by Dr. Naidu and a multidisciplinary panel of experts from specialties that included cardiac critical care, interventional cardiology, surgery, nursing, emergency medicine, and heart failure – was published online Jan. 31 in the Journal of the Society for Cardiovascular Angiography and Interventions, with simultaneous publication in the Journal of the American College of Cardiology.  

It maintains the five-stage pyramid of CS, starting with “at risk” and moving through “beginning,” “classic,” “deteriorating,” and “extremis” but now includes gradations of severity within each stage and pathways by which patients progress or recover.

“Progression across the SCAI shock stage continuum is a dynamic process, incorporating new information as available, and patient trajectories are important both for communication among clinicians and for decisionmaking regarding the next level of care and therapeutics,” the panel writes.

The second iteration adds a streamlined table incorporating commonly seen variables, based on lessons learned from validation studies and clinician experience.

“While keeping the same initial framework of looking at the three components of staging – the physical exam, the biochemical markers, and hemodynamics – we’ve made it very clear that there are some factors in each of these that are most typically seen. And then there are other factors that are consistent with that stage but don’t necessarily have to be seen, ... are not typically seen in that stage, or [are] not always present at that stage,” Dr. Naidu told this news organization.

The refined CS classification system provides more granularity on cardiac arrest as a risk modifier, which now excludes very brief episodes with rapid response to defibrillation and comprises only those patients who have impaired mental status with unknown neurologic recovery status after cardiopulmonary resuscitation.

Lactate level and thresholds have been highlighted to detect hypoperfusion but may be dissociated from hemodynamics in cases such as chronic heart failure.

In addition, patients may have other manifestations of end-organ hypoperfusion with a normal lactate level, and there are also important causes of an elevated lactate level other than shock.

The revision proposes a three-axis model of CS evaluation and prognostication that integrates shock severity, clinical phenotype, and risk modifiers as distinct elements that should be applied to individualize patient management.

The revision also places more emphasis on the trajectory of the patient with CS through hospitalization, including a “hub and spoke” model for transfer of higher-risk patients, including those with a deteriorating SCAI shock stage.

“It is our desire and belief that the revised SCAI SHOCK stage classification system will enhance both clinical care and CS research trial design,” the panel writes.

This statement has been endorsed by the American College of Cardiology, American College of Emergency Physicians, American Heart Association, European Society of Cardiology Association for Acute Cardiovascular Care, International Society for Heart and Lung Transplantation, Society of Critical Care Medicine, and Society of Thoracic Surgeons.

This research had no commercial funding. Dr. Naidu has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.

“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”

Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”

Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.

“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”

For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.

As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.

“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.

Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:

• Stroke: HR, 1.52; burden, 4.03
• Transient ischemic attack: HR, 1.49; burden, 1.84
• Dysrhythmias: HR, 1.69; burden, 19.86
• Ischemic heart disease: HR, 1.66; burden, 7.28
• Heart failure: HR, 1.72; burden, 11.61
• Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
• Pulmonary embolism: HR, 2.93; burden, 5.47
• Deep vein thrombosis: HR, 2.09; burden, 4.18
• Pericarditis: HR, 1.85, burden, 0.98
• Myocarditis: HR, 5.38; burden, 0.31

Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.

The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.

The overall results were also consistent when compared with the historical control subjects.

“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”

With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”

Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”

The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.

The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.

“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”

Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”

Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.

“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”

For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.

As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.

“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.

Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:

• Stroke: HR, 1.52; burden, 4.03
• Transient ischemic attack: HR, 1.49; burden, 1.84
• Dysrhythmias: HR, 1.69; burden, 19.86
• Ischemic heart disease: HR, 1.66; burden, 7.28
• Heart failure: HR, 1.72; burden, 11.61
• Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
• Pulmonary embolism: HR, 2.93; burden, 5.47
• Deep vein thrombosis: HR, 2.09; burden, 4.18
• Pericarditis: HR, 1.85, burden, 0.98
• Myocarditis: HR, 5.38; burden, 0.31

Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.

The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.

The overall results were also consistent when compared with the historical control subjects.

“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”

With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”

Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”

The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.

The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.

“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”

Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”

Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.

“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”

For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.

As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.

“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.

Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:

• Stroke: HR, 1.52; burden, 4.03
• Transient ischemic attack: HR, 1.49; burden, 1.84
• Dysrhythmias: HR, 1.69; burden, 19.86
• Ischemic heart disease: HR, 1.66; burden, 7.28
• Heart failure: HR, 1.72; burden, 11.61
• Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
• Pulmonary embolism: HR, 2.93; burden, 5.47
• Deep vein thrombosis: HR, 2.09; burden, 4.18
• Pericarditis: HR, 1.85, burden, 0.98
• Myocarditis: HR, 5.38; burden, 0.31

Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.

The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.

The overall results were also consistent when compared with the historical control subjects.

“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”

With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”

Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”

The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.

The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Aggressive up-front combination therapy, more lofty treatment goals, and earlier and more frequent reassessments to guide treatment are improving care of patients with pulmonary arterial hypertension (PAH) while at the same time making it more complex.

A larger number of oral and generic treatment options have in some respects ushered in more management ease. But overall, “I don’t know if management of these patients has ever been more complicated, given the treatment options and strategies,” said Murali M. Chakinala, MD, professor of medicine at Washington University, St. Louis. “We’re always thinking through approaches.”

Diagnosis continues to be challenging given the rarity of PAH and its nonspecific presentation – and in some cases it’s now harder. Experts such as Dr. Chakinala are seeing increasing number of aging patients with left heart disease, chronic kidney disease, and other comorbidities who have significant precapillary pulmonary hypertension and who exhibit hemodynamics consistent with PAH, or group 1 PH.

The question experts face is, do such patients have “true PAH,” as do a reported 25-50 people per million, or do they have another type of PH in the classification schema – or a mixture?

Deciding which patients “really fit into group 1 and should be managed like group 1,” Dr. Chakinala said, requires clinical acumen and has important implications, as patients with PAH are the main beneficiaries of vasodilator therapy. Most other patients with PH will not respond to or tolerate such treatment.

“These older patients may be getting PAH through different mechanisms than our younger patients, but because we define PAH through hemodynamic criteria and by ruling out other obvious explanations, they all get lumped together,” said Dr. Chakinala. “We need to parse these patients out better in the future, much like our oncology colleagues are doing.”

Yale Rosen/Wikimedia Commons/Creative Commons Attribution-Share Alike 2.0 Generi

Personalized medicine hopefully is the next horizon for this condition, characterized by severe remodeling of the distal pulmonary arteries. Researchers are pushing to achieve deep phenotyping, identify biomarkers and improve risk assessment tools.

And with 80 or so centers now accredited by the Pulmonary Hypertension Association as Pulmonary Hypertension Care Centers, referred patients are accessing clinical trials of new nonvasodilatory drugs. Currently available therapies improve hemodynamics and symptoms, and can slow disease progression, but are not truly disease modifying, sources say.

“The endothelin, nitric oxide, and prostacyclin pathways have been exhaustively studied and we now have great drugs for those pathways,” said Dr. Chakinala, who leads the PHA’s scientific leadership council. But “we’re not going to put a greater dent into this disease until we have new drugs that work on different biologic pathways.”
 

Diagnostic challenges

The diagnosis of PAH – a remarkably heterogeneous condition that encompasses heritable forms and idiopathic forms, and that comprises a broad mix of predisposing conditions and exposures, from scleroderma to methamphetamine use – is still too often missed or delayed. Delayed diagnoses and misdiagnoses of PAH and other types of PH have been reported in up to 85% of at-risk patients, according to a 2016 literature review.

Being able to pivot from thinking about common pulmonary ailments or heart failure to considering PAH is a key part of earlier diagnosis and better treatment outcomes. “If someone has unexplained dyspnea or if they’re treated for other lung diseases and are not improving, think about a screening echocardiogram,” said Timothy L. Williamson, MD, vice president of quality and safety and a pulmonary and critical care physician at the University of Kansas Health Center, Kansas City.

One of the most common reasons Dr. Chakinala sees for missed diagnoses are right heart catheterizations that are incomplete or misinterpreted. (Right heart catheterizations are required to confirm the diagnosis.) “One can’t simply measure pressures and stop,” he said. “We need the full hemodynamic profile to know that it’s truly precapillary PAH ... and we need proper interpretation of [elements like] the waveforms.”

The 2019 World Symposium on Pulmonary Hypertension shifted the definition of PH from an arbitrarily defined mean pulmonary arterial pressure of at least 25 mm Hg at rest (as measured by right heart catheterization) to a more scientifically determined mPAP of at least 20 mm Hg.

The classification document also requires pulmonary vascular resistance (PVR) of at least 3 Wood units in the definition of all forms of precapillary PH. PAH specifically is defined as the presence of mPAP of at least 20 mm Hg, PVR of at least 3 Wood units, and pulmonary arterial wedge pressure 15 mm Hg or less.
 

Trends in treatment

The value of initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 (PDE5) inhibitor in treatment-naive PAH was cemented in 2015 by the AMBITION trial. The primary endpoint (death, PAH hospitalization, or unsatisfactory clinical response) occurred in 18%, 34%, and 28% of patients who were randomized, respectively, to combination therapy, monotherapy with the ERA ambrisentan, or monotherapy with the PDE-5 inhibitor tadalafil – and in 31% of the two monotherapy groups combined.

The trial reported a 50% reduction in the primary endpoint in the combination-therapy group versus the pooled monotherapy group, as well as greater reductions in N-terminal of the prohormone brain natriuretic peptide levels, more satisfactory clinical response and greater improvement in 6-minute walking distance.

In practice, a minority of patients – typically older patients with multiple comorbidities – still receive initial monotherapy with sequential add-on therapies based on tolerance, but “for the most part PAH patients will start on combination therapy, most commonly with a ERA and PDE5 inhibitor,” Dr. Chakinala said.

For patients who are not improving on the ERA-PDE5 inhibitor approach – typically those who remain in the intermediate-risk category for intermediate-term mortality – substitution of the PDE5 inhibitor with the soluble guanylate cyclase stimulator riociguat may be considered, he and Dr. Williamson said. Clinical improvement with this substitution was demonstrated in the REPLACE trial.

Experts at PH care centers are also utilizing triple therapy for patients who do not improve to low-risk status after 2-4 months of dual combination therapy. The availability of oral prostacyclin analogues (selexipag and treprostinil) makes it easier to consider adding these agents early on, Dr. Chakinala and Dr. Richardson said.

Patients who fall into the high-risk category, at any point, are still best managed with parenteral prostacyclin analogues, Dr. Chakinala said.

In general, said Dr. Williamson, who also directs the University of Kansas Pulmonary Hypertension Comprehensive Care Center, “the PH community tends to be fairly aggressive up front, and with a low threshold for using prostacyclin analogues.”

The agents are “always part of the picture for someone who is really ill, in functional class IV, or has really impaired right ventricular function,” he said. “And we’re finding increased roles in patients who are not as ill but still have decompensated right ventricular dysfunction. It’s something we now consider.”

Recently published research on up-front oral triple therapy suggests possible benefit for some patients – but it’s far from conclusive, said Dr. Chakinala. The TRITON study randomized treatment-naive patients to the traditional ERA-PDE5 combination and either oral selexipag (a selective prostacyclin receptor agonist) or placebo as a third agent. It found no significant difference in reduction in PVR, the primary outcome, at week 26. However, the authors reported a “possible signal” for improved long-term outcomes with triple therapy.

“Based on this best evidence from a randomized clinical trial, I think it’s unfair to say that all patients should be on triple combination therapy right out of the gate,” he said. “Having said that, more recent [European] data showed that two drugs fell short of the mark in some patients, with high rates of clinical progression. And even in AMBITION, there were a number of patients in the combination arm who didn’t have a robust response.”

A 2021 retrospective analysis from the French Pulmonary Hypertension Registry – one of the European studies – assessed survival with monotherapy, dual therapy, or triple-combination therapy (two orals with a parenteral prostacyclin), and found no difference between monotherapy and dual therapy in high-risk patients.

Experts have been upping the ante, therefore, on early assessment and frequent reassessment of treatment response. Not long ago, patients were typically reassessed 6-12 months after the initiation of treatment. Now, experts at the PH care centers want to assess patients at 3-4 months and adjust or intensify treatment regimens for those who don’t yet qualify as low risk using a multidimensional risk score calculator.

The REVEAL (Registry to Evaluate Early and Long-Term PAH Management) risk score calculator, for instance, predicts the probability of 1-year survival and assigns patients to a strata of risk level based on either 12 or 6 variables (for the full or “lite” versions).]

Even better monitoring and risk assessment is needed, however, to “help sift out which patients are not improving enough on initial therapy or who are starting to fall off after being on a regimen for a period of time,” Dr. Chakinala said.

Today, with a network of accredited centers of expertise and a desire and need for many patients to remain close to home, Dr. Chakinala encourages finding a balance. Well-resourced clinicians can strive for early diagnosis and management – potentially initiating ERA–PDE-5 inhibitor combination therapy – but still should collaborate with PH experts.

“It’s a good idea to comanage these patients and let the experts see them periodically to help you determine when your patient may be declining,” he said. “The timetable for reassessment, the complexity of the reassessment, and the need to escalate to more advanced therapies has never been more important.”
 

Research highlights

Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.

Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.

“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference

“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.

Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”

Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.

The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.

In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”

Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.

Aggressive up-front combination therapy, more lofty treatment goals, and earlier and more frequent reassessments to guide treatment are improving care of patients with pulmonary arterial hypertension (PAH) while at the same time making it more complex.

A larger number of oral and generic treatment options have in some respects ushered in more management ease. But overall, “I don’t know if management of these patients has ever been more complicated, given the treatment options and strategies,” said Murali M. Chakinala, MD, professor of medicine at Washington University, St. Louis. “We’re always thinking through approaches.”

Diagnosis continues to be challenging given the rarity of PAH and its nonspecific presentation – and in some cases it’s now harder. Experts such as Dr. Chakinala are seeing increasing number of aging patients with left heart disease, chronic kidney disease, and other comorbidities who have significant precapillary pulmonary hypertension and who exhibit hemodynamics consistent with PAH, or group 1 PH.

The question experts face is, do such patients have “true PAH,” as do a reported 25-50 people per million, or do they have another type of PH in the classification schema – or a mixture?

Deciding which patients “really fit into group 1 and should be managed like group 1,” Dr. Chakinala said, requires clinical acumen and has important implications, as patients with PAH are the main beneficiaries of vasodilator therapy. Most other patients with PH will not respond to or tolerate such treatment.

“These older patients may be getting PAH through different mechanisms than our younger patients, but because we define PAH through hemodynamic criteria and by ruling out other obvious explanations, they all get lumped together,” said Dr. Chakinala. “We need to parse these patients out better in the future, much like our oncology colleagues are doing.”

Yale Rosen/Wikimedia Commons/Creative Commons Attribution-Share Alike 2.0 Generi

Personalized medicine hopefully is the next horizon for this condition, characterized by severe remodeling of the distal pulmonary arteries. Researchers are pushing to achieve deep phenotyping, identify biomarkers and improve risk assessment tools.

And with 80 or so centers now accredited by the Pulmonary Hypertension Association as Pulmonary Hypertension Care Centers, referred patients are accessing clinical trials of new nonvasodilatory drugs. Currently available therapies improve hemodynamics and symptoms, and can slow disease progression, but are not truly disease modifying, sources say.

“The endothelin, nitric oxide, and prostacyclin pathways have been exhaustively studied and we now have great drugs for those pathways,” said Dr. Chakinala, who leads the PHA’s scientific leadership council. But “we’re not going to put a greater dent into this disease until we have new drugs that work on different biologic pathways.”
 

Diagnostic challenges

The diagnosis of PAH – a remarkably heterogeneous condition that encompasses heritable forms and idiopathic forms, and that comprises a broad mix of predisposing conditions and exposures, from scleroderma to methamphetamine use – is still too often missed or delayed. Delayed diagnoses and misdiagnoses of PAH and other types of PH have been reported in up to 85% of at-risk patients, according to a 2016 literature review.

Being able to pivot from thinking about common pulmonary ailments or heart failure to considering PAH is a key part of earlier diagnosis and better treatment outcomes. “If someone has unexplained dyspnea or if they’re treated for other lung diseases and are not improving, think about a screening echocardiogram,” said Timothy L. Williamson, MD, vice president of quality and safety and a pulmonary and critical care physician at the University of Kansas Health Center, Kansas City.

One of the most common reasons Dr. Chakinala sees for missed diagnoses are right heart catheterizations that are incomplete or misinterpreted. (Right heart catheterizations are required to confirm the diagnosis.) “One can’t simply measure pressures and stop,” he said. “We need the full hemodynamic profile to know that it’s truly precapillary PAH ... and we need proper interpretation of [elements like] the waveforms.”

The 2019 World Symposium on Pulmonary Hypertension shifted the definition of PH from an arbitrarily defined mean pulmonary arterial pressure of at least 25 mm Hg at rest (as measured by right heart catheterization) to a more scientifically determined mPAP of at least 20 mm Hg.

The classification document also requires pulmonary vascular resistance (PVR) of at least 3 Wood units in the definition of all forms of precapillary PH. PAH specifically is defined as the presence of mPAP of at least 20 mm Hg, PVR of at least 3 Wood units, and pulmonary arterial wedge pressure 15 mm Hg or less.
 

Trends in treatment

The value of initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 (PDE5) inhibitor in treatment-naive PAH was cemented in 2015 by the AMBITION trial. The primary endpoint (death, PAH hospitalization, or unsatisfactory clinical response) occurred in 18%, 34%, and 28% of patients who were randomized, respectively, to combination therapy, monotherapy with the ERA ambrisentan, or monotherapy with the PDE-5 inhibitor tadalafil – and in 31% of the two monotherapy groups combined.

The trial reported a 50% reduction in the primary endpoint in the combination-therapy group versus the pooled monotherapy group, as well as greater reductions in N-terminal of the prohormone brain natriuretic peptide levels, more satisfactory clinical response and greater improvement in 6-minute walking distance.

In practice, a minority of patients – typically older patients with multiple comorbidities – still receive initial monotherapy with sequential add-on therapies based on tolerance, but “for the most part PAH patients will start on combination therapy, most commonly with a ERA and PDE5 inhibitor,” Dr. Chakinala said.

For patients who are not improving on the ERA-PDE5 inhibitor approach – typically those who remain in the intermediate-risk category for intermediate-term mortality – substitution of the PDE5 inhibitor with the soluble guanylate cyclase stimulator riociguat may be considered, he and Dr. Williamson said. Clinical improvement with this substitution was demonstrated in the REPLACE trial.

Experts at PH care centers are also utilizing triple therapy for patients who do not improve to low-risk status after 2-4 months of dual combination therapy. The availability of oral prostacyclin analogues (selexipag and treprostinil) makes it easier to consider adding these agents early on, Dr. Chakinala and Dr. Richardson said.

Patients who fall into the high-risk category, at any point, are still best managed with parenteral prostacyclin analogues, Dr. Chakinala said.

In general, said Dr. Williamson, who also directs the University of Kansas Pulmonary Hypertension Comprehensive Care Center, “the PH community tends to be fairly aggressive up front, and with a low threshold for using prostacyclin analogues.”

The agents are “always part of the picture for someone who is really ill, in functional class IV, or has really impaired right ventricular function,” he said. “And we’re finding increased roles in patients who are not as ill but still have decompensated right ventricular dysfunction. It’s something we now consider.”

Recently published research on up-front oral triple therapy suggests possible benefit for some patients – but it’s far from conclusive, said Dr. Chakinala. The TRITON study randomized treatment-naive patients to the traditional ERA-PDE5 combination and either oral selexipag (a selective prostacyclin receptor agonist) or placebo as a third agent. It found no significant difference in reduction in PVR, the primary outcome, at week 26. However, the authors reported a “possible signal” for improved long-term outcomes with triple therapy.

“Based on this best evidence from a randomized clinical trial, I think it’s unfair to say that all patients should be on triple combination therapy right out of the gate,” he said. “Having said that, more recent [European] data showed that two drugs fell short of the mark in some patients, with high rates of clinical progression. And even in AMBITION, there were a number of patients in the combination arm who didn’t have a robust response.”

A 2021 retrospective analysis from the French Pulmonary Hypertension Registry – one of the European studies – assessed survival with monotherapy, dual therapy, or triple-combination therapy (two orals with a parenteral prostacyclin), and found no difference between monotherapy and dual therapy in high-risk patients.

Experts have been upping the ante, therefore, on early assessment and frequent reassessment of treatment response. Not long ago, patients were typically reassessed 6-12 months after the initiation of treatment. Now, experts at the PH care centers want to assess patients at 3-4 months and adjust or intensify treatment regimens for those who don’t yet qualify as low risk using a multidimensional risk score calculator.

The REVEAL (Registry to Evaluate Early and Long-Term PAH Management) risk score calculator, for instance, predicts the probability of 1-year survival and assigns patients to a strata of risk level based on either 12 or 6 variables (for the full or “lite” versions).]

Even better monitoring and risk assessment is needed, however, to “help sift out which patients are not improving enough on initial therapy or who are starting to fall off after being on a regimen for a period of time,” Dr. Chakinala said.

Today, with a network of accredited centers of expertise and a desire and need for many patients to remain close to home, Dr. Chakinala encourages finding a balance. Well-resourced clinicians can strive for early diagnosis and management – potentially initiating ERA–PDE-5 inhibitor combination therapy – but still should collaborate with PH experts.

“It’s a good idea to comanage these patients and let the experts see them periodically to help you determine when your patient may be declining,” he said. “The timetable for reassessment, the complexity of the reassessment, and the need to escalate to more advanced therapies has never been more important.”
 

Research highlights

Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.

Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.

“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference

“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.

Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”

Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.

The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.

In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”

Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.

Aggressive up-front combination therapy, more lofty treatment goals, and earlier and more frequent reassessments to guide treatment are improving care of patients with pulmonary arterial hypertension (PAH) while at the same time making it more complex.

A larger number of oral and generic treatment options have in some respects ushered in more management ease. But overall, “I don’t know if management of these patients has ever been more complicated, given the treatment options and strategies,” said Murali M. Chakinala, MD, professor of medicine at Washington University, St. Louis. “We’re always thinking through approaches.”

Diagnosis continues to be challenging given the rarity of PAH and its nonspecific presentation – and in some cases it’s now harder. Experts such as Dr. Chakinala are seeing increasing number of aging patients with left heart disease, chronic kidney disease, and other comorbidities who have significant precapillary pulmonary hypertension and who exhibit hemodynamics consistent with PAH, or group 1 PH.

The question experts face is, do such patients have “true PAH,” as do a reported 25-50 people per million, or do they have another type of PH in the classification schema – or a mixture?

Deciding which patients “really fit into group 1 and should be managed like group 1,” Dr. Chakinala said, requires clinical acumen and has important implications, as patients with PAH are the main beneficiaries of vasodilator therapy. Most other patients with PH will not respond to or tolerate such treatment.

“These older patients may be getting PAH through different mechanisms than our younger patients, but because we define PAH through hemodynamic criteria and by ruling out other obvious explanations, they all get lumped together,” said Dr. Chakinala. “We need to parse these patients out better in the future, much like our oncology colleagues are doing.”

Yale Rosen/Wikimedia Commons/Creative Commons Attribution-Share Alike 2.0 Generi

Personalized medicine hopefully is the next horizon for this condition, characterized by severe remodeling of the distal pulmonary arteries. Researchers are pushing to achieve deep phenotyping, identify biomarkers and improve risk assessment tools.

And with 80 or so centers now accredited by the Pulmonary Hypertension Association as Pulmonary Hypertension Care Centers, referred patients are accessing clinical trials of new nonvasodilatory drugs. Currently available therapies improve hemodynamics and symptoms, and can slow disease progression, but are not truly disease modifying, sources say.

“The endothelin, nitric oxide, and prostacyclin pathways have been exhaustively studied and we now have great drugs for those pathways,” said Dr. Chakinala, who leads the PHA’s scientific leadership council. But “we’re not going to put a greater dent into this disease until we have new drugs that work on different biologic pathways.”
 

Diagnostic challenges

The diagnosis of PAH – a remarkably heterogeneous condition that encompasses heritable forms and idiopathic forms, and that comprises a broad mix of predisposing conditions and exposures, from scleroderma to methamphetamine use – is still too often missed or delayed. Delayed diagnoses and misdiagnoses of PAH and other types of PH have been reported in up to 85% of at-risk patients, according to a 2016 literature review.

Being able to pivot from thinking about common pulmonary ailments or heart failure to considering PAH is a key part of earlier diagnosis and better treatment outcomes. “If someone has unexplained dyspnea or if they’re treated for other lung diseases and are not improving, think about a screening echocardiogram,” said Timothy L. Williamson, MD, vice president of quality and safety and a pulmonary and critical care physician at the University of Kansas Health Center, Kansas City.

One of the most common reasons Dr. Chakinala sees for missed diagnoses are right heart catheterizations that are incomplete or misinterpreted. (Right heart catheterizations are required to confirm the diagnosis.) “One can’t simply measure pressures and stop,” he said. “We need the full hemodynamic profile to know that it’s truly precapillary PAH ... and we need proper interpretation of [elements like] the waveforms.”

The 2019 World Symposium on Pulmonary Hypertension shifted the definition of PH from an arbitrarily defined mean pulmonary arterial pressure of at least 25 mm Hg at rest (as measured by right heart catheterization) to a more scientifically determined mPAP of at least 20 mm Hg.

The classification document also requires pulmonary vascular resistance (PVR) of at least 3 Wood units in the definition of all forms of precapillary PH. PAH specifically is defined as the presence of mPAP of at least 20 mm Hg, PVR of at least 3 Wood units, and pulmonary arterial wedge pressure 15 mm Hg or less.
 

Trends in treatment

The value of initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 (PDE5) inhibitor in treatment-naive PAH was cemented in 2015 by the AMBITION trial. The primary endpoint (death, PAH hospitalization, or unsatisfactory clinical response) occurred in 18%, 34%, and 28% of patients who were randomized, respectively, to combination therapy, monotherapy with the ERA ambrisentan, or monotherapy with the PDE-5 inhibitor tadalafil – and in 31% of the two monotherapy groups combined.

The trial reported a 50% reduction in the primary endpoint in the combination-therapy group versus the pooled monotherapy group, as well as greater reductions in N-terminal of the prohormone brain natriuretic peptide levels, more satisfactory clinical response and greater improvement in 6-minute walking distance.

In practice, a minority of patients – typically older patients with multiple comorbidities – still receive initial monotherapy with sequential add-on therapies based on tolerance, but “for the most part PAH patients will start on combination therapy, most commonly with a ERA and PDE5 inhibitor,” Dr. Chakinala said.

For patients who are not improving on the ERA-PDE5 inhibitor approach – typically those who remain in the intermediate-risk category for intermediate-term mortality – substitution of the PDE5 inhibitor with the soluble guanylate cyclase stimulator riociguat may be considered, he and Dr. Williamson said. Clinical improvement with this substitution was demonstrated in the REPLACE trial.

Experts at PH care centers are also utilizing triple therapy for patients who do not improve to low-risk status after 2-4 months of dual combination therapy. The availability of oral prostacyclin analogues (selexipag and treprostinil) makes it easier to consider adding these agents early on, Dr. Chakinala and Dr. Richardson said.

Patients who fall into the high-risk category, at any point, are still best managed with parenteral prostacyclin analogues, Dr. Chakinala said.

In general, said Dr. Williamson, who also directs the University of Kansas Pulmonary Hypertension Comprehensive Care Center, “the PH community tends to be fairly aggressive up front, and with a low threshold for using prostacyclin analogues.”

The agents are “always part of the picture for someone who is really ill, in functional class IV, or has really impaired right ventricular function,” he said. “And we’re finding increased roles in patients who are not as ill but still have decompensated right ventricular dysfunction. It’s something we now consider.”

Recently published research on up-front oral triple therapy suggests possible benefit for some patients – but it’s far from conclusive, said Dr. Chakinala. The TRITON study randomized treatment-naive patients to the traditional ERA-PDE5 combination and either oral selexipag (a selective prostacyclin receptor agonist) or placebo as a third agent. It found no significant difference in reduction in PVR, the primary outcome, at week 26. However, the authors reported a “possible signal” for improved long-term outcomes with triple therapy.

“Based on this best evidence from a randomized clinical trial, I think it’s unfair to say that all patients should be on triple combination therapy right out of the gate,” he said. “Having said that, more recent [European] data showed that two drugs fell short of the mark in some patients, with high rates of clinical progression. And even in AMBITION, there were a number of patients in the combination arm who didn’t have a robust response.”

A 2021 retrospective analysis from the French Pulmonary Hypertension Registry – one of the European studies – assessed survival with monotherapy, dual therapy, or triple-combination therapy (two orals with a parenteral prostacyclin), and found no difference between monotherapy and dual therapy in high-risk patients.

Experts have been upping the ante, therefore, on early assessment and frequent reassessment of treatment response. Not long ago, patients were typically reassessed 6-12 months after the initiation of treatment. Now, experts at the PH care centers want to assess patients at 3-4 months and adjust or intensify treatment regimens for those who don’t yet qualify as low risk using a multidimensional risk score calculator.

The REVEAL (Registry to Evaluate Early and Long-Term PAH Management) risk score calculator, for instance, predicts the probability of 1-year survival and assigns patients to a strata of risk level based on either 12 or 6 variables (for the full or “lite” versions).]

Even better monitoring and risk assessment is needed, however, to “help sift out which patients are not improving enough on initial therapy or who are starting to fall off after being on a regimen for a period of time,” Dr. Chakinala said.

Today, with a network of accredited centers of expertise and a desire and need for many patients to remain close to home, Dr. Chakinala encourages finding a balance. Well-resourced clinicians can strive for early diagnosis and management – potentially initiating ERA–PDE-5 inhibitor combination therapy – but still should collaborate with PH experts.

“It’s a good idea to comanage these patients and let the experts see them periodically to help you determine when your patient may be declining,” he said. “The timetable for reassessment, the complexity of the reassessment, and the need to escalate to more advanced therapies has never been more important.”
 

Research highlights

Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.

Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.

“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference

“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.

Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”

Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.

The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.

In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”

Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.

Vasculitis of the coronary arteries is a well-recognized acute complication of Kawasaki disease, but the long-term risk of cardiovascular (CV) sequelae does not appear to be clinically meaningful for most patients, according to results from an analysis of data presented at the annual meeting of the Canadian Rheumatology Association.

For patients and parents, these data provide “a message of reassurance,” according to Jennifer J.Y. Lee, MD, a pediatric rheumatologist affiliated with the Hospital for Sick Children, Toronto.

The long-term outcomes were characterized as reassuring even though rates of hypertension, major adverse cardiac events (MACE), and death from CV events were higher in patients with Kawasaki disease relative to controls in a retrospective data-linkage study. In fact, these differences were highly statistically significant, but the absolute differences were extremely small.

For this analysis, the 1,174 patients diagnosed with Kawasaki disease at Dr. Lee’s institution between 1991 and 2008 were compared in a 10:1 ratio to 11,740 controls matched for factors such as age, sex, ethnicity, and geographic region. The median follow-up period was 20 years, and the maximum was 28 years.
 

Adjusted CV risks are significant

In an adjusted Cox proportional hazard ratio model, patients in the Kawasaki group had a more than twofold increase in risk for hypertension (aHR, 2.3; P < .0001) and all-cause mortality (aHR, 2.5; P = .009). They also had more than a 10-fold increase in risk for MACE (aHR, 10.3; P < .0001).

These statistics belie the clinical relevance, according to Dr. Lee. Because of the very low rates of all the measured events in both groups, there was just one more case of hypertension per 1,250 patient-years of follow-up, one more case of MACE per 833 patient-years of follow-up, and one more death for 3,846 patient years of follow-up.

Moreover, when these outcomes were graphed over time, most events occurred during the acute period or in the initial years of follow-up.

“There was not a constant increase in risk of these outcomes over time for patients with Kawasaki disease relative to the controls,” Dr. Lee reported. “The long-term prognosis for Kawasaki patients remains favorable.”

European group reports similar results

Similar results from a single-center experience were published 3 years ago. In that study, 207 Kawasaki patients treated at the University of Lausanne (Switzerland) were followed for 30 years. Complications after the acute phase were characterized as “rare.”

For example, only three patients (1.4%) had a subsequent episode of myocardial ischemia. All three had developed a coronary aneurysm during the acute phase of Kawasaki disease. The authors of that study reported that children who had not received immunoglobulins during the acute phase or who developed Kawasaki disease outside of the usual age range were more likely to have subsequent events, such as disease recurrence.

Other studies of long-term CV outcomes in patients with Kawasaki disease generally show similar data, according to James T. Gaensbauer, MD, a pediatric infectious disease specialist at the Mayo Clinic, Rochester, Minn.

“I generally agree with the premise that major complications are rare when you compare a cohort of patients with Kawasaki disease with the general population,” Dr. Gaensbauer said. However, he added, “I do not think you can say no one needs to worry.”
 

Severity of acute disease might matter

During the acute phase of Kawasaki disease, the arterial damage varies. As suggested in the University of Lausanne follow-up, patients with significant coronary aneurysms do appear to be at greater risk of long-term complications. Dr. Gaensbauer cited a statement from the American Heart Association that noted a higher risk of CV sequelae from Kawasaki disease with a greater or more severe coronary aneurysm or in the face of other evidence of damage to the arterial tree.

“The clinical course within the first 2 years of Kawasaki disease appears to be important for risk of CV complications after this time,” Dr. Gaensbauer said.

The absolute risk of CV events in patients with a more complicated acute course of Kawasaki disease remains incompletely understood, but Dr. Gaensbauer said that there are several sets of data, including these new data from the Hospital for Sick Children, that suggest that the overall prognosis is good. However, he cautioned that this reassurance does not necessarily apply to children with a difficult acute course.

According to the 2017 AHA statement on Kawasaki disease, risk stratification based on echocardiography and other measures after the acute phase of Kawasaki disease are reasonable to determine if long-term follow-up is needed. In those without abnormalities, it is reasonable to forgo further cardiology assessment.

Dr. Lee and Dr. Gaensbauer reported having no potential conflicts of interest.

Vasculitis of the coronary arteries is a well-recognized acute complication of Kawasaki disease, but the long-term risk of cardiovascular (CV) sequelae does not appear to be clinically meaningful for most patients, according to results from an analysis of data presented at the annual meeting of the Canadian Rheumatology Association.

For patients and parents, these data provide “a message of reassurance,” according to Jennifer J.Y. Lee, MD, a pediatric rheumatologist affiliated with the Hospital for Sick Children, Toronto.

The long-term outcomes were characterized as reassuring even though rates of hypertension, major adverse cardiac events (MACE), and death from CV events were higher in patients with Kawasaki disease relative to controls in a retrospective data-linkage study. In fact, these differences were highly statistically significant, but the absolute differences were extremely small.

For this analysis, the 1,174 patients diagnosed with Kawasaki disease at Dr. Lee’s institution between 1991 and 2008 were compared in a 10:1 ratio to 11,740 controls matched for factors such as age, sex, ethnicity, and geographic region. The median follow-up period was 20 years, and the maximum was 28 years.
 

Adjusted CV risks are significant

In an adjusted Cox proportional hazard ratio model, patients in the Kawasaki group had a more than twofold increase in risk for hypertension (aHR, 2.3; P < .0001) and all-cause mortality (aHR, 2.5; P = .009). They also had more than a 10-fold increase in risk for MACE (aHR, 10.3; P < .0001).

These statistics belie the clinical relevance, according to Dr. Lee. Because of the very low rates of all the measured events in both groups, there was just one more case of hypertension per 1,250 patient-years of follow-up, one more case of MACE per 833 patient-years of follow-up, and one more death for 3,846 patient years of follow-up.

Moreover, when these outcomes were graphed over time, most events occurred during the acute period or in the initial years of follow-up.

“There was not a constant increase in risk of these outcomes over time for patients with Kawasaki disease relative to the controls,” Dr. Lee reported. “The long-term prognosis for Kawasaki patients remains favorable.”

European group reports similar results

Similar results from a single-center experience were published 3 years ago. In that study, 207 Kawasaki patients treated at the University of Lausanne (Switzerland) were followed for 30 years. Complications after the acute phase were characterized as “rare.”

For example, only three patients (1.4%) had a subsequent episode of myocardial ischemia. All three had developed a coronary aneurysm during the acute phase of Kawasaki disease. The authors of that study reported that children who had not received immunoglobulins during the acute phase or who developed Kawasaki disease outside of the usual age range were more likely to have subsequent events, such as disease recurrence.

Other studies of long-term CV outcomes in patients with Kawasaki disease generally show similar data, according to James T. Gaensbauer, MD, a pediatric infectious disease specialist at the Mayo Clinic, Rochester, Minn.

“I generally agree with the premise that major complications are rare when you compare a cohort of patients with Kawasaki disease with the general population,” Dr. Gaensbauer said. However, he added, “I do not think you can say no one needs to worry.”
 

Severity of acute disease might matter

During the acute phase of Kawasaki disease, the arterial damage varies. As suggested in the University of Lausanne follow-up, patients with significant coronary aneurysms do appear to be at greater risk of long-term complications. Dr. Gaensbauer cited a statement from the American Heart Association that noted a higher risk of CV sequelae from Kawasaki disease with a greater or more severe coronary aneurysm or in the face of other evidence of damage to the arterial tree.

“The clinical course within the first 2 years of Kawasaki disease appears to be important for risk of CV complications after this time,” Dr. Gaensbauer said.

The absolute risk of CV events in patients with a more complicated acute course of Kawasaki disease remains incompletely understood, but Dr. Gaensbauer said that there are several sets of data, including these new data from the Hospital for Sick Children, that suggest that the overall prognosis is good. However, he cautioned that this reassurance does not necessarily apply to children with a difficult acute course.

According to the 2017 AHA statement on Kawasaki disease, risk stratification based on echocardiography and other measures after the acute phase of Kawasaki disease are reasonable to determine if long-term follow-up is needed. In those without abnormalities, it is reasonable to forgo further cardiology assessment.

Dr. Lee and Dr. Gaensbauer reported having no potential conflicts of interest.

Vasculitis of the coronary arteries is a well-recognized acute complication of Kawasaki disease, but the long-term risk of cardiovascular (CV) sequelae does not appear to be clinically meaningful for most patients, according to results from an analysis of data presented at the annual meeting of the Canadian Rheumatology Association.

For patients and parents, these data provide “a message of reassurance,” according to Jennifer J.Y. Lee, MD, a pediatric rheumatologist affiliated with the Hospital for Sick Children, Toronto.

The long-term outcomes were characterized as reassuring even though rates of hypertension, major adverse cardiac events (MACE), and death from CV events were higher in patients with Kawasaki disease relative to controls in a retrospective data-linkage study. In fact, these differences were highly statistically significant, but the absolute differences were extremely small.

For this analysis, the 1,174 patients diagnosed with Kawasaki disease at Dr. Lee’s institution between 1991 and 2008 were compared in a 10:1 ratio to 11,740 controls matched for factors such as age, sex, ethnicity, and geographic region. The median follow-up period was 20 years, and the maximum was 28 years.
 

Adjusted CV risks are significant

In an adjusted Cox proportional hazard ratio model, patients in the Kawasaki group had a more than twofold increase in risk for hypertension (aHR, 2.3; P < .0001) and all-cause mortality (aHR, 2.5; P = .009). They also had more than a 10-fold increase in risk for MACE (aHR, 10.3; P < .0001).

These statistics belie the clinical relevance, according to Dr. Lee. Because of the very low rates of all the measured events in both groups, there was just one more case of hypertension per 1,250 patient-years of follow-up, one more case of MACE per 833 patient-years of follow-up, and one more death for 3,846 patient years of follow-up.

Moreover, when these outcomes were graphed over time, most events occurred during the acute period or in the initial years of follow-up.

“There was not a constant increase in risk of these outcomes over time for patients with Kawasaki disease relative to the controls,” Dr. Lee reported. “The long-term prognosis for Kawasaki patients remains favorable.”

European group reports similar results

Similar results from a single-center experience were published 3 years ago. In that study, 207 Kawasaki patients treated at the University of Lausanne (Switzerland) were followed for 30 years. Complications after the acute phase were characterized as “rare.”

For example, only three patients (1.4%) had a subsequent episode of myocardial ischemia. All three had developed a coronary aneurysm during the acute phase of Kawasaki disease. The authors of that study reported that children who had not received immunoglobulins during the acute phase or who developed Kawasaki disease outside of the usual age range were more likely to have subsequent events, such as disease recurrence.

Other studies of long-term CV outcomes in patients with Kawasaki disease generally show similar data, according to James T. Gaensbauer, MD, a pediatric infectious disease specialist at the Mayo Clinic, Rochester, Minn.

“I generally agree with the premise that major complications are rare when you compare a cohort of patients with Kawasaki disease with the general population,” Dr. Gaensbauer said. However, he added, “I do not think you can say no one needs to worry.”
 

Severity of acute disease might matter

During the acute phase of Kawasaki disease, the arterial damage varies. As suggested in the University of Lausanne follow-up, patients with significant coronary aneurysms do appear to be at greater risk of long-term complications. Dr. Gaensbauer cited a statement from the American Heart Association that noted a higher risk of CV sequelae from Kawasaki disease with a greater or more severe coronary aneurysm or in the face of other evidence of damage to the arterial tree.

“The clinical course within the first 2 years of Kawasaki disease appears to be important for risk of CV complications after this time,” Dr. Gaensbauer said.

The absolute risk of CV events in patients with a more complicated acute course of Kawasaki disease remains incompletely understood, but Dr. Gaensbauer said that there are several sets of data, including these new data from the Hospital for Sick Children, that suggest that the overall prognosis is good. However, he cautioned that this reassurance does not necessarily apply to children with a difficult acute course.

According to the 2017 AHA statement on Kawasaki disease, risk stratification based on echocardiography and other measures after the acute phase of Kawasaki disease are reasonable to determine if long-term follow-up is needed. In those without abnormalities, it is reasonable to forgo further cardiology assessment.

Dr. Lee and Dr. Gaensbauer reported having no potential conflicts of interest.

Right now, more than 106,600 people in the United States are on the national transplant waiting list, each hoping to hear soon that a lung, kidney, heart, or other vital organ has been found for them. It’s the promise not just of a new organ, but a new life.

Well before they are placed on that list, transplant candidates, as they’re known, are evaluated with a battery of tests and exams to be sure they are infection free, their other organs are healthy, and that all their vaccinations are up to date.

Now, COVID vaccinations – and some people’s resistance to them – have turned what used to be routine preparation controversial.

In January, a 31-year-old Boston father of two declined to get the COVID-19 vaccine, and Brigham and Women’s Hospital officials removed him from the heart transplant waiting list. And in North Carolina, a 38-year-old man in need of a kidney transplant said he, too, was denied the organ when he declined to get the vaccination.

Those are just two of the most recent cases. The decisions by the transplant centers to remove the candidates from the waiting list have set off a national debate among ethicists, family members, doctors, patients, and others.

On social media and in conversation, the question persists: Is removing them from the list unfair and cruel, or simply business as usual to keep the patient as healthy as possible and the transplant as successful as possible?

Two recent tweets sum up the debate.

“The people responsible for this should be charged with attempted homicide,” one Twitter user said, while another suggested that the more accurate way to headline the news about a transplant candidate refusing the COVID-19 vaccine would be: “Patient voluntarily forfeits donor organ.”

Doctors and ethics experts, as well as other patients on the waiting list, say it’s simply good medicine to require the COVID vaccine, along with a host of other pretransplant requirements.
 

Transplant protocols

“Transplant medicine has always been a strong promoter of vaccination,” said Silas Prescod Norman, MD, a clinical associate professor of nephrology and internal medicine at the University of Michigan, Ann Arbor. He is a kidney specialist who works in the university’s transplant clinic.

Requiring the COVID vaccine is in line with requirements to get numerous other vaccines, he said.“Promoting the COVID vaccine among our transplant candidates and recipients is just an extension of our usual practice.

“In transplantation, first and foremost is patient safety,” Dr. Norman said. “And we know that solid organ transplant patients are at substantially higher risk of contracting COVID than nontransplant patients.”

After the transplant, they are placed on immunosuppressant drugs, that weaken the immune system while also decreasing the body’s ability to reject the new organ.

“We know now, because there is good data about the vaccine to show that people who are on transplant medications are less likely to make detectable antibodies after vaccination,” said Dr. Norman, who’s also a medical adviser for the American Kidney Fund, a nonprofit that provides kidney health information and financial assistance for dialysis.

And this is not a surprise because of the immunosuppressive effects, he said. “So it only makes sense to get people vaccinated before transplantation.”

Researchers compared the cases of more than 17,000 people who had received organ transplants and were hospitalized from April to November 2020, either for COVID (1,682 of them) or other health issues. Those who had COVID were more likely to have complications and to die in the hospital than those who did not have it.
 

Vaccination guidelines, policies

Federal COVID-19 treatment guidelines from the National Institutes of Health state that transplant patients on immunosuppressant drugs used after the procedure should be considered at a higher risk of getting severe COVID if infected.

In a joint statement from the American Society of Transplant Surgeons, the American Society of Transplantation, and the International Society for Heart and Lung Transplantation, the organizations say they “strongly recommend that all eligible children and adult transplant candidates and recipients be vaccinated with a COVID-19 vaccine [and booster] that is approved or authorized in their jurisdiction. Whenever possible, vaccination should occur prior to transplantation.” Ideally, it should be completed at least 2 weeks before the transplant.

The organizations also “support the development of institutional policies regarding pretransplant vaccination. We believe that this is in the best interest of the transplant candidate, optimizing their chances of getting through the perioperative and posttransplant periods without severe COVID-19 disease, especially at times of greater infection prevalence.”

Officials at Brigham and Women’s Hospital, where the 31-year-old father was removed from the list, issued a statement that reads, in part: “Our Mass General Brigham health care system requires several [Centers for Disease Control and Prevention]-recommended vaccines, including the COVID-19 vaccine, and lifestyle behaviors for transplant candidates to create both the best chance for a successful operation and to optimize the patient’s survival after transplantation, given that their immune system is drastically suppressed. Patients are not active on the wait list without this.”
 

Ethics amid organ shortage

“Organs are scarce,” said Arthur L. Caplan, PhD, director of the division of medical ethics at New York University Langone Medical Center. That makes the goal of choosing the very best candidates for success even more crucial.

“You try to maximize the chance the organ will work,” he said. Pretransplant vaccination is one way.

The shortage is most severe for kidney transplants. In 2020, according to federal statistics, more than 91,000 kidney transplants were needed, but fewer than 23,000 were received. During 2021, 41,354 transplants were done, an increase of nearly 6% over the previous year. The total includes kidneys, hearts, lungs, and other organs, with kidneys accounting for more than 24,000 of the total.

Even with the rise in transplant numbers, supply does not meet demand. According to federal statistics, 17 people in the United States die each day waiting for an organ transplant. Every 9 minutes, someone is added to the waiting list.

“This isn’t and it shouldn’t be a fight about the COVID vaccine,” Dr. Caplan said. “This isn’t an issue about punishing non-COVID vaccinators. It’s deciding who is going to get a scarce organ.”

“A lot of people [opposed to removing the nonvaccinated from the list] think: ‘Oh, they are just killing those people who won’t take a COVID vaccine.’ That’s not what is going on.”

The transplant candidate must be in the best possible shape overall, Dr. Caplan and doctors agreed. Someone who is smoking, drinking heavily, or abusing drugs isn’t going to the top of the list either. And for other procedures, such as bariatric surgery or knee surgery, some patients are told first to lose weight before a surgeon will operate.

The worry about side effects from the vaccine, which some patients have cited as a concern, is misplaced, Dr. Caplan said. What transplant candidates who refuse the COVID vaccine may not be thinking about is that they are facing a serious operation and will be on numerous anti-rejection drugs, with side effects, after the surgery.

“So to be worried about the side effects of a COVID vaccine is irrational,” he said.
 

Transplants: The process

The patients who were recently removed from the transplant list could seek care and a transplant at an alternate center, said Anne Paschke, a spokesperson for the United Network for Organ Sharing, a nonprofit group that is under contract with the federal government and operates the national Organ Procurement and Transplantation Network (OPTN).

“Transplant hospitals decide which patients to add to the wait list based on their own criteria and medical judgment to create the best chance for a positive transplant outcome,” she said. That’s done with the understanding that patients will help with their medical care.

So, if one program won’t accept a patient, another may. But, if a patient turned down at one center due to refusing to get the COVID vaccine tries another center, the requirements at that hospital may be the same, she said.

OPTN maintains a list of transplant centers. As of Jan. 28, there were 251 transplant centers, according to UNOS, which manages the waiting list, matches donors and recipients, and strives for equity, among other duties.
 

Pretransplant refusers not typical

“The cases we are seeing are outliers,” Dr. Caplan said of the handful of known candidates who have refused the vaccine. Most ask their doctor exactly what they need to do to live and follow those instructions.

Dr. Norman agreed. Most of the kidney patients he cares for who are hoping for a transplant have been on dialysis, “which they do not like. They are doing whatever they can to make sure they don’t go back on dialysis. As a group, they tend to be very adherent, very safety conscious because they understand their risk and they understand the gift they have received [or will receive] through transplantation. They want to do everything they can to respect and protect that gift.”

Not surprisingly, some on the transplant list who are vaccinated have strong opinions about those who refuse to get the vaccine. Dana J. Ufkes, 61, a Seattle realtor, has been on the kidney transplant list – this time – since 2003, hoping for her third transplant. When asked if potential recipients should be removed from the list if they refuse the COVID vaccine, her answer was immediate: “Absolutely.”

At age 17, Ms. Ufkes got a serious kidney infection that went undiagnosed and untreated. Her kidney health worsened, and she needed a transplant. She got her first one in 1986, then again in 1992.

“They last longer than they used to,” she said. But not forever. (According to the American Kidney Fund, transplants from a living kidney donor last about 15-20 years; from a deceased donor, 10-15.)

The decision to decline the vaccine is, of course, each person’s choice, Ms. Ufkes said. But “if they don’t want to be vaccinated [and still want to be on the list], I think that’s BS.”

Citing the lack of organs, “it’s not like they are handing these out like jellybeans.”

A version of this article first appeared on WebMD.com.

Right now, more than 106,600 people in the United States are on the national transplant waiting list, each hoping to hear soon that a lung, kidney, heart, or other vital organ has been found for them. It’s the promise not just of a new organ, but a new life.

Well before they are placed on that list, transplant candidates, as they’re known, are evaluated with a battery of tests and exams to be sure they are infection free, their other organs are healthy, and that all their vaccinations are up to date.

Now, COVID vaccinations – and some people’s resistance to them – have turned what used to be routine preparation controversial.

In January, a 31-year-old Boston father of two declined to get the COVID-19 vaccine, and Brigham and Women’s Hospital officials removed him from the heart transplant waiting list. And in North Carolina, a 38-year-old man in need of a kidney transplant said he, too, was denied the organ when he declined to get the vaccination.

Those are just two of the most recent cases. The decisions by the transplant centers to remove the candidates from the waiting list have set off a national debate among ethicists, family members, doctors, patients, and others.

On social media and in conversation, the question persists: Is removing them from the list unfair and cruel, or simply business as usual to keep the patient as healthy as possible and the transplant as successful as possible?

Two recent tweets sum up the debate.

“The people responsible for this should be charged with attempted homicide,” one Twitter user said, while another suggested that the more accurate way to headline the news about a transplant candidate refusing the COVID-19 vaccine would be: “Patient voluntarily forfeits donor organ.”

Doctors and ethics experts, as well as other patients on the waiting list, say it’s simply good medicine to require the COVID vaccine, along with a host of other pretransplant requirements.
 

Transplant protocols

“Transplant medicine has always been a strong promoter of vaccination,” said Silas Prescod Norman, MD, a clinical associate professor of nephrology and internal medicine at the University of Michigan, Ann Arbor. He is a kidney specialist who works in the university’s transplant clinic.

Requiring the COVID vaccine is in line with requirements to get numerous other vaccines, he said.“Promoting the COVID vaccine among our transplant candidates and recipients is just an extension of our usual practice.

“In transplantation, first and foremost is patient safety,” Dr. Norman said. “And we know that solid organ transplant patients are at substantially higher risk of contracting COVID than nontransplant patients.”

After the transplant, they are placed on immunosuppressant drugs, that weaken the immune system while also decreasing the body’s ability to reject the new organ.

“We know now, because there is good data about the vaccine to show that people who are on transplant medications are less likely to make detectable antibodies after vaccination,” said Dr. Norman, who’s also a medical adviser for the American Kidney Fund, a nonprofit that provides kidney health information and financial assistance for dialysis.

And this is not a surprise because of the immunosuppressive effects, he said. “So it only makes sense to get people vaccinated before transplantation.”

Researchers compared the cases of more than 17,000 people who had received organ transplants and were hospitalized from April to November 2020, either for COVID (1,682 of them) or other health issues. Those who had COVID were more likely to have complications and to die in the hospital than those who did not have it.
 

Vaccination guidelines, policies

Federal COVID-19 treatment guidelines from the National Institutes of Health state that transplant patients on immunosuppressant drugs used after the procedure should be considered at a higher risk of getting severe COVID if infected.

In a joint statement from the American Society of Transplant Surgeons, the American Society of Transplantation, and the International Society for Heart and Lung Transplantation, the organizations say they “strongly recommend that all eligible children and adult transplant candidates and recipients be vaccinated with a COVID-19 vaccine [and booster] that is approved or authorized in their jurisdiction. Whenever possible, vaccination should occur prior to transplantation.” Ideally, it should be completed at least 2 weeks before the transplant.

The organizations also “support the development of institutional policies regarding pretransplant vaccination. We believe that this is in the best interest of the transplant candidate, optimizing their chances of getting through the perioperative and posttransplant periods without severe COVID-19 disease, especially at times of greater infection prevalence.”

Officials at Brigham and Women’s Hospital, where the 31-year-old father was removed from the list, issued a statement that reads, in part: “Our Mass General Brigham health care system requires several [Centers for Disease Control and Prevention]-recommended vaccines, including the COVID-19 vaccine, and lifestyle behaviors for transplant candidates to create both the best chance for a successful operation and to optimize the patient’s survival after transplantation, given that their immune system is drastically suppressed. Patients are not active on the wait list without this.”
 

Ethics amid organ shortage

“Organs are scarce,” said Arthur L. Caplan, PhD, director of the division of medical ethics at New York University Langone Medical Center. That makes the goal of choosing the very best candidates for success even more crucial.

“You try to maximize the chance the organ will work,” he said. Pretransplant vaccination is one way.

The shortage is most severe for kidney transplants. In 2020, according to federal statistics, more than 91,000 kidney transplants were needed, but fewer than 23,000 were received. During 2021, 41,354 transplants were done, an increase of nearly 6% over the previous year. The total includes kidneys, hearts, lungs, and other organs, with kidneys accounting for more than 24,000 of the total.

Even with the rise in transplant numbers, supply does not meet demand. According to federal statistics, 17 people in the United States die each day waiting for an organ transplant. Every 9 minutes, someone is added to the waiting list.

“This isn’t and it shouldn’t be a fight about the COVID vaccine,” Dr. Caplan said. “This isn’t an issue about punishing non-COVID vaccinators. It’s deciding who is going to get a scarce organ.”

“A lot of people [opposed to removing the nonvaccinated from the list] think: ‘Oh, they are just killing those people who won’t take a COVID vaccine.’ That’s not what is going on.”

The transplant candidate must be in the best possible shape overall, Dr. Caplan and doctors agreed. Someone who is smoking, drinking heavily, or abusing drugs isn’t going to the top of the list either. And for other procedures, such as bariatric surgery or knee surgery, some patients are told first to lose weight before a surgeon will operate.

The worry about side effects from the vaccine, which some patients have cited as a concern, is misplaced, Dr. Caplan said. What transplant candidates who refuse the COVID vaccine may not be thinking about is that they are facing a serious operation and will be on numerous anti-rejection drugs, with side effects, after the surgery.

“So to be worried about the side effects of a COVID vaccine is irrational,” he said.
 

Transplants: The process

The patients who were recently removed from the transplant list could seek care and a transplant at an alternate center, said Anne Paschke, a spokesperson for the United Network for Organ Sharing, a nonprofit group that is under contract with the federal government and operates the national Organ Procurement and Transplantation Network (OPTN).

“Transplant hospitals decide which patients to add to the wait list based on their own criteria and medical judgment to create the best chance for a positive transplant outcome,” she said. That’s done with the understanding that patients will help with their medical care.

So, if one program won’t accept a patient, another may. But, if a patient turned down at one center due to refusing to get the COVID vaccine tries another center, the requirements at that hospital may be the same, she said.

OPTN maintains a list of transplant centers. As of Jan. 28, there were 251 transplant centers, according to UNOS, which manages the waiting list, matches donors and recipients, and strives for equity, among other duties.
 

Pretransplant refusers not typical

“The cases we are seeing are outliers,” Dr. Caplan said of the handful of known candidates who have refused the vaccine. Most ask their doctor exactly what they need to do to live and follow those instructions.

Dr. Norman agreed. Most of the kidney patients he cares for who are hoping for a transplant have been on dialysis, “which they do not like. They are doing whatever they can to make sure they don’t go back on dialysis. As a group, they tend to be very adherent, very safety conscious because they understand their risk and they understand the gift they have received [or will receive] through transplantation. They want to do everything they can to respect and protect that gift.”

Not surprisingly, some on the transplant list who are vaccinated have strong opinions about those who refuse to get the vaccine. Dana J. Ufkes, 61, a Seattle realtor, has been on the kidney transplant list – this time – since 2003, hoping for her third transplant. When asked if potential recipients should be removed from the list if they refuse the COVID vaccine, her answer was immediate: “Absolutely.”

At age 17, Ms. Ufkes got a serious kidney infection that went undiagnosed and untreated. Her kidney health worsened, and she needed a transplant. She got her first one in 1986, then again in 1992.

“They last longer than they used to,” she said. But not forever. (According to the American Kidney Fund, transplants from a living kidney donor last about 15-20 years; from a deceased donor, 10-15.)

The decision to decline the vaccine is, of course, each person’s choice, Ms. Ufkes said. But “if they don’t want to be vaccinated [and still want to be on the list], I think that’s BS.”

Citing the lack of organs, “it’s not like they are handing these out like jellybeans.”

A version of this article first appeared on WebMD.com.

Right now, more than 106,600 people in the United States are on the national transplant waiting list, each hoping to hear soon that a lung, kidney, heart, or other vital organ has been found for them. It’s the promise not just of a new organ, but a new life.

Well before they are placed on that list, transplant candidates, as they’re known, are evaluated with a battery of tests and exams to be sure they are infection free, their other organs are healthy, and that all their vaccinations are up to date.

Now, COVID vaccinations – and some people’s resistance to them – have turned what used to be routine preparation controversial.

In January, a 31-year-old Boston father of two declined to get the COVID-19 vaccine, and Brigham and Women’s Hospital officials removed him from the heart transplant waiting list. And in North Carolina, a 38-year-old man in need of a kidney transplant said he, too, was denied the organ when he declined to get the vaccination.

Those are just two of the most recent cases. The decisions by the transplant centers to remove the candidates from the waiting list have set off a national debate among ethicists, family members, doctors, patients, and others.

On social media and in conversation, the question persists: Is removing them from the list unfair and cruel, or simply business as usual to keep the patient as healthy as possible and the transplant as successful as possible?

Two recent tweets sum up the debate.

“The people responsible for this should be charged with attempted homicide,” one Twitter user said, while another suggested that the more accurate way to headline the news about a transplant candidate refusing the COVID-19 vaccine would be: “Patient voluntarily forfeits donor organ.”

Doctors and ethics experts, as well as other patients on the waiting list, say it’s simply good medicine to require the COVID vaccine, along with a host of other pretransplant requirements.
 

Transplant protocols

“Transplant medicine has always been a strong promoter of vaccination,” said Silas Prescod Norman, MD, a clinical associate professor of nephrology and internal medicine at the University of Michigan, Ann Arbor. He is a kidney specialist who works in the university’s transplant clinic.

Requiring the COVID vaccine is in line with requirements to get numerous other vaccines, he said.“Promoting the COVID vaccine among our transplant candidates and recipients is just an extension of our usual practice.

“In transplantation, first and foremost is patient safety,” Dr. Norman said. “And we know that solid organ transplant patients are at substantially higher risk of contracting COVID than nontransplant patients.”

After the transplant, they are placed on immunosuppressant drugs, that weaken the immune system while also decreasing the body’s ability to reject the new organ.

“We know now, because there is good data about the vaccine to show that people who are on transplant medications are less likely to make detectable antibodies after vaccination,” said Dr. Norman, who’s also a medical adviser for the American Kidney Fund, a nonprofit that provides kidney health information and financial assistance for dialysis.

And this is not a surprise because of the immunosuppressive effects, he said. “So it only makes sense to get people vaccinated before transplantation.”

Researchers compared the cases of more than 17,000 people who had received organ transplants and were hospitalized from April to November 2020, either for COVID (1,682 of them) or other health issues. Those who had COVID were more likely to have complications and to die in the hospital than those who did not have it.
 

Vaccination guidelines, policies

Federal COVID-19 treatment guidelines from the National Institutes of Health state that transplant patients on immunosuppressant drugs used after the procedure should be considered at a higher risk of getting severe COVID if infected.

In a joint statement from the American Society of Transplant Surgeons, the American Society of Transplantation, and the International Society for Heart and Lung Transplantation, the organizations say they “strongly recommend that all eligible children and adult transplant candidates and recipients be vaccinated with a COVID-19 vaccine [and booster] that is approved or authorized in their jurisdiction. Whenever possible, vaccination should occur prior to transplantation.” Ideally, it should be completed at least 2 weeks before the transplant.

The organizations also “support the development of institutional policies regarding pretransplant vaccination. We believe that this is in the best interest of the transplant candidate, optimizing their chances of getting through the perioperative and posttransplant periods without severe COVID-19 disease, especially at times of greater infection prevalence.”

Officials at Brigham and Women’s Hospital, where the 31-year-old father was removed from the list, issued a statement that reads, in part: “Our Mass General Brigham health care system requires several [Centers for Disease Control and Prevention]-recommended vaccines, including the COVID-19 vaccine, and lifestyle behaviors for transplant candidates to create both the best chance for a successful operation and to optimize the patient’s survival after transplantation, given that their immune system is drastically suppressed. Patients are not active on the wait list without this.”
 

Ethics amid organ shortage

“Organs are scarce,” said Arthur L. Caplan, PhD, director of the division of medical ethics at New York University Langone Medical Center. That makes the goal of choosing the very best candidates for success even more crucial.

“You try to maximize the chance the organ will work,” he said. Pretransplant vaccination is one way.

The shortage is most severe for kidney transplants. In 2020, according to federal statistics, more than 91,000 kidney transplants were needed, but fewer than 23,000 were received. During 2021, 41,354 transplants were done, an increase of nearly 6% over the previous year. The total includes kidneys, hearts, lungs, and other organs, with kidneys accounting for more than 24,000 of the total.

Even with the rise in transplant numbers, supply does not meet demand. According to federal statistics, 17 people in the United States die each day waiting for an organ transplant. Every 9 minutes, someone is added to the waiting list.

“This isn’t and it shouldn’t be a fight about the COVID vaccine,” Dr. Caplan said. “This isn’t an issue about punishing non-COVID vaccinators. It’s deciding who is going to get a scarce organ.”

“A lot of people [opposed to removing the nonvaccinated from the list] think: ‘Oh, they are just killing those people who won’t take a COVID vaccine.’ That’s not what is going on.”

The transplant candidate must be in the best possible shape overall, Dr. Caplan and doctors agreed. Someone who is smoking, drinking heavily, or abusing drugs isn’t going to the top of the list either. And for other procedures, such as bariatric surgery or knee surgery, some patients are told first to lose weight before a surgeon will operate.

The worry about side effects from the vaccine, which some patients have cited as a concern, is misplaced, Dr. Caplan said. What transplant candidates who refuse the COVID vaccine may not be thinking about is that they are facing a serious operation and will be on numerous anti-rejection drugs, with side effects, after the surgery.

“So to be worried about the side effects of a COVID vaccine is irrational,” he said.
 

Transplants: The process

The patients who were recently removed from the transplant list could seek care and a transplant at an alternate center, said Anne Paschke, a spokesperson for the United Network for Organ Sharing, a nonprofit group that is under contract with the federal government and operates the national Organ Procurement and Transplantation Network (OPTN).

“Transplant hospitals decide which patients to add to the wait list based on their own criteria and medical judgment to create the best chance for a positive transplant outcome,” she said. That’s done with the understanding that patients will help with their medical care.

So, if one program won’t accept a patient, another may. But, if a patient turned down at one center due to refusing to get the COVID vaccine tries another center, the requirements at that hospital may be the same, she said.

OPTN maintains a list of transplant centers. As of Jan. 28, there were 251 transplant centers, according to UNOS, which manages the waiting list, matches donors and recipients, and strives for equity, among other duties.
 

Pretransplant refusers not typical

“The cases we are seeing are outliers,” Dr. Caplan said of the handful of known candidates who have refused the vaccine. Most ask their doctor exactly what they need to do to live and follow those instructions.

Dr. Norman agreed. Most of the kidney patients he cares for who are hoping for a transplant have been on dialysis, “which they do not like. They are doing whatever they can to make sure they don’t go back on dialysis. As a group, they tend to be very adherent, very safety conscious because they understand their risk and they understand the gift they have received [or will receive] through transplantation. They want to do everything they can to respect and protect that gift.”

Not surprisingly, some on the transplant list who are vaccinated have strong opinions about those who refuse to get the vaccine. Dana J. Ufkes, 61, a Seattle realtor, has been on the kidney transplant list – this time – since 2003, hoping for her third transplant. When asked if potential recipients should be removed from the list if they refuse the COVID vaccine, her answer was immediate: “Absolutely.”

At age 17, Ms. Ufkes got a serious kidney infection that went undiagnosed and untreated. Her kidney health worsened, and she needed a transplant. She got her first one in 1986, then again in 1992.

“They last longer than they used to,” she said. But not forever. (According to the American Kidney Fund, transplants from a living kidney donor last about 15-20 years; from a deceased donor, 10-15.)

The decision to decline the vaccine is, of course, each person’s choice, Ms. Ufkes said. But “if they don’t want to be vaccinated [and still want to be on the list], I think that’s BS.”

Citing the lack of organs, “it’s not like they are handing these out like jellybeans.”

A version of this article first appeared on WebMD.com.

Among healthy middle-aged men, those who were more anxious were more likely to develop high levels of multiple biomarkers of cardiometabolic risk over a 40-year follow-up in a new study.

“By middle adulthood, higher anxiety levels are associated with stable differences” in biomarkers of risk for coronary artery disease (CAD), stroke, and type 2 diabetes, which “are maintained into older ages,” the researchers wrote.

Anxious individuals “may experience deteriorations in cardiometabolic health earlier in life and remain on a stable trajectory of heightened risk into older ages,” they concluded.

The study, led by Lewina Lee, PhD, was published online Jan. 24, 2022, in the Journal of the American Heart Association.

“Men who had higher levels of anxiety at the beginning of the study had consistently higher biological risk for cardiometabolic disease than less anxious men from midlife into old age,” Dr. Lee, assistant professor of psychiatry, Boston University, summarized in an email.

Clinicians may not screen for heart disease and diabetes, and/or only discuss lifestyle modifications when patients are older or have the first signs of disease, she added.

However, the study findings “suggest that worries and anxiety are associated with preclinical pathophysiological processes that tend to culminate in cardiometabolic disease” and show “the importance of screening for mental health difficulties, such as worries and anxiety, in men as early as in their 30s and 40s,” she stressed.

Since most of the men were White (97%) and veterans (94%), “it would be important for future studies to evaluate if these associations exist among women, people from diverse racial and ethnic groups, and in more socioeconomically varying samples, and to consider how anxiety may relate to the development of cardiometabolic risk in much younger individuals than those in our study,” Dr. Lee said in a press release from the American Heart Association.

“This study adds to the growing body of research that link psychological health to cardiovascular risk,” Glenn N. Levine, MD, who was not involved with this research, told this news organization in an email.

“We know that factors such as depression and stress can increase cardiac risk; this study further supports that anxiety can as well,” added Dr. Levine, chief of cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston.

“Everyone experiences some anxiety in their life,” he added. However, “if a provider senses that a patient’s anxiety is far beyond the ‘normal’ that we all have from time to time, and it is seemingly adversely impacting both their psychological and physical health, it would be reasonable to suggest to the patient that it might be useful to speak with a mental health professional, and if the patient is receptive, to then make a formal consultation or referral,” said Dr. Levine, who was writing group chair of a recent AHA Scientific Statement on mind-heart-body connection.
 

Neuroticism and worry

Several studies have linked anxiety to a greater risk of cardiometabolic disease onset, Dr. Lee and colleagues wrote, but it is unclear if anxious individuals have a steadily worsening risk as they age, or if they have a higher risk in middle age, which stays the same in older age.

To investigate this, they analyzed data from 1561 men who were seen at the VA Boston outpatient clinic and did not have CAD, type 2 diabetes, stroke, or cancer when they enrolled in the Normative Aging Study.

The men had a mean age of 53 years (range, 33-84) in 1975 and were followed until 2015 or until dropout from the study or death.

At baseline, the study participants filled in the Eysenck Personality Inventory, which assesses neuroticism, and also responded to a scale indicating how much they worry about 20 issues (excluding health).

“Neuroticism,” the researchers explained, “is a tendency to perceive experiences as threatening, feel that challenges are uncontrollable, and experience frequent and disproportionately intense negative emotions,” such as fear, anxiety, sadness, and anger, “across many situations.”

“Worry refers to attempts to solve a problem where future outcome is uncertain and potentially positive or negative,” Dr. Lee noted. Although worry can be healthy and lead to constructive solutions, “it may be unhealthy, especially when it becomes uncontrollable and interferes with day-to-day functioning.”

Of note, in 1980, the American Psychiatric Association removed the term neurosis from its diagnostic manual. What was previously called neurosis is included as part of generalized anxiety disorder; GAD also encompasses excessive worry.
 

Cardiometabolic risk from midlife to old age

The men in the current study had on-site physical examinations every 3-5 years.

The researchers calculated the men’s cardiometabolic risk score (from 0 to 7) by assigning 1 point each for the following: systolic blood pressure greater than 130 mm Hg, diastolic blood pressure greater than 85 mm Hg, total cholesterol of at least 240 mg/dL, triglycerides of at least 150 mg/dL, body mass index of at least 30 kg/m2, glucose of at least 100 mg/dL, and erythrocyte sedimentation rate of at least 14 mm/hour.

Alternatively, patients were assigned a point each for taking medication that could affect these markers (except for body mass index).

Overall, on average, at baseline, the men had a cardiometabolic risk score of 2.9. From age 33-65, this score increased to 3.8, and then it did not increase as much later on.

That is, the cardiometabolic risk score increased by 0.8 per decade until age 65, followed by a slower increase of 0.5 per decade.

At all ages, men with higher levels of neuroticism or worry had a higher cardiometabolic risk score

Each additional standard deviation of neuroticism was associated with a 13% increased risk of having six or more of the seven cardiometabolic risk markers during follow-up, after adjusting for age, demographics, and family history of CAD, but the relationship was attenuated after also adjusting for health behaviors (for example, smoking, alcohol consumption, physical activity, and past-year physician visit at baseline).

Similarly, each additional standard deviation of worry was associated with a 10% increased risk of having six or more of the seven cardiometabolic risk markers during follow-up after the same adjustments, and was also no longer significantly different after the same further adjustments.

The research was supported by grants from the National Institutes of Health and a Senior Research Career Scientist Award from the Office of Research and Development, Department of Veterans Affairs. The Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center and is supported by the VA Cooperative Studies Program/Epidemiological Research Centers. The study authors and Dr. Levine disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among healthy middle-aged men, those who were more anxious were more likely to develop high levels of multiple biomarkers of cardiometabolic risk over a 40-year follow-up in a new study.

“By middle adulthood, higher anxiety levels are associated with stable differences” in biomarkers of risk for coronary artery disease (CAD), stroke, and type 2 diabetes, which “are maintained into older ages,” the researchers wrote.

Anxious individuals “may experience deteriorations in cardiometabolic health earlier in life and remain on a stable trajectory of heightened risk into older ages,” they concluded.

The study, led by Lewina Lee, PhD, was published online Jan. 24, 2022, in the Journal of the American Heart Association.

“Men who had higher levels of anxiety at the beginning of the study had consistently higher biological risk for cardiometabolic disease than less anxious men from midlife into old age,” Dr. Lee, assistant professor of psychiatry, Boston University, summarized in an email.

Clinicians may not screen for heart disease and diabetes, and/or only discuss lifestyle modifications when patients are older or have the first signs of disease, she added.

However, the study findings “suggest that worries and anxiety are associated with preclinical pathophysiological processes that tend to culminate in cardiometabolic disease” and show “the importance of screening for mental health difficulties, such as worries and anxiety, in men as early as in their 30s and 40s,” she stressed.

Since most of the men were White (97%) and veterans (94%), “it would be important for future studies to evaluate if these associations exist among women, people from diverse racial and ethnic groups, and in more socioeconomically varying samples, and to consider how anxiety may relate to the development of cardiometabolic risk in much younger individuals than those in our study,” Dr. Lee said in a press release from the American Heart Association.

“This study adds to the growing body of research that link psychological health to cardiovascular risk,” Glenn N. Levine, MD, who was not involved with this research, told this news organization in an email.

“We know that factors such as depression and stress can increase cardiac risk; this study further supports that anxiety can as well,” added Dr. Levine, chief of cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston.

“Everyone experiences some anxiety in their life,” he added. However, “if a provider senses that a patient’s anxiety is far beyond the ‘normal’ that we all have from time to time, and it is seemingly adversely impacting both their psychological and physical health, it would be reasonable to suggest to the patient that it might be useful to speak with a mental health professional, and if the patient is receptive, to then make a formal consultation or referral,” said Dr. Levine, who was writing group chair of a recent AHA Scientific Statement on mind-heart-body connection.
 

Neuroticism and worry

Several studies have linked anxiety to a greater risk of cardiometabolic disease onset, Dr. Lee and colleagues wrote, but it is unclear if anxious individuals have a steadily worsening risk as they age, or if they have a higher risk in middle age, which stays the same in older age.

To investigate this, they analyzed data from 1561 men who were seen at the VA Boston outpatient clinic and did not have CAD, type 2 diabetes, stroke, or cancer when they enrolled in the Normative Aging Study.

The men had a mean age of 53 years (range, 33-84) in 1975 and were followed until 2015 or until dropout from the study or death.

At baseline, the study participants filled in the Eysenck Personality Inventory, which assesses neuroticism, and also responded to a scale indicating how much they worry about 20 issues (excluding health).

“Neuroticism,” the researchers explained, “is a tendency to perceive experiences as threatening, feel that challenges are uncontrollable, and experience frequent and disproportionately intense negative emotions,” such as fear, anxiety, sadness, and anger, “across many situations.”

“Worry refers to attempts to solve a problem where future outcome is uncertain and potentially positive or negative,” Dr. Lee noted. Although worry can be healthy and lead to constructive solutions, “it may be unhealthy, especially when it becomes uncontrollable and interferes with day-to-day functioning.”

Of note, in 1980, the American Psychiatric Association removed the term neurosis from its diagnostic manual. What was previously called neurosis is included as part of generalized anxiety disorder; GAD also encompasses excessive worry.
 

Cardiometabolic risk from midlife to old age

The men in the current study had on-site physical examinations every 3-5 years.

The researchers calculated the men’s cardiometabolic risk score (from 0 to 7) by assigning 1 point each for the following: systolic blood pressure greater than 130 mm Hg, diastolic blood pressure greater than 85 mm Hg, total cholesterol of at least 240 mg/dL, triglycerides of at least 150 mg/dL, body mass index of at least 30 kg/m2, glucose of at least 100 mg/dL, and erythrocyte sedimentation rate of at least 14 mm/hour.

Alternatively, patients were assigned a point each for taking medication that could affect these markers (except for body mass index).

Overall, on average, at baseline, the men had a cardiometabolic risk score of 2.9. From age 33-65, this score increased to 3.8, and then it did not increase as much later on.

That is, the cardiometabolic risk score increased by 0.8 per decade until age 65, followed by a slower increase of 0.5 per decade.

At all ages, men with higher levels of neuroticism or worry had a higher cardiometabolic risk score

Each additional standard deviation of neuroticism was associated with a 13% increased risk of having six or more of the seven cardiometabolic risk markers during follow-up, after adjusting for age, demographics, and family history of CAD, but the relationship was attenuated after also adjusting for health behaviors (for example, smoking, alcohol consumption, physical activity, and past-year physician visit at baseline).

Similarly, each additional standard deviation of worry was associated with a 10% increased risk of having six or more of the seven cardiometabolic risk markers during follow-up after the same adjustments, and was also no longer significantly different after the same further adjustments.

The research was supported by grants from the National Institutes of Health and a Senior Research Career Scientist Award from the Office of Research and Development, Department of Veterans Affairs. The Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center and is supported by the VA Cooperative Studies Program/Epidemiological Research Centers. The study authors and Dr. Levine disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among healthy middle-aged men, those who were more anxious were more likely to develop high levels of multiple biomarkers of cardiometabolic risk over a 40-year follow-up in a new study.

“By middle adulthood, higher anxiety levels are associated with stable differences” in biomarkers of risk for coronary artery disease (CAD), stroke, and type 2 diabetes, which “are maintained into older ages,” the researchers wrote.

Anxious individuals “may experience deteriorations in cardiometabolic health earlier in life and remain on a stable trajectory of heightened risk into older ages,” they concluded.

The study, led by Lewina Lee, PhD, was published online Jan. 24, 2022, in the Journal of the American Heart Association.

“Men who had higher levels of anxiety at the beginning of the study had consistently higher biological risk for cardiometabolic disease than less anxious men from midlife into old age,” Dr. Lee, assistant professor of psychiatry, Boston University, summarized in an email.

Clinicians may not screen for heart disease and diabetes, and/or only discuss lifestyle modifications when patients are older or have the first signs of disease, she added.

However, the study findings “suggest that worries and anxiety are associated with preclinical pathophysiological processes that tend to culminate in cardiometabolic disease” and show “the importance of screening for mental health difficulties, such as worries and anxiety, in men as early as in their 30s and 40s,” she stressed.

Since most of the men were White (97%) and veterans (94%), “it would be important for future studies to evaluate if these associations exist among women, people from diverse racial and ethnic groups, and in more socioeconomically varying samples, and to consider how anxiety may relate to the development of cardiometabolic risk in much younger individuals than those in our study,” Dr. Lee said in a press release from the American Heart Association.

“This study adds to the growing body of research that link psychological health to cardiovascular risk,” Glenn N. Levine, MD, who was not involved with this research, told this news organization in an email.

“We know that factors such as depression and stress can increase cardiac risk; this study further supports that anxiety can as well,” added Dr. Levine, chief of cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston.

“Everyone experiences some anxiety in their life,” he added. However, “if a provider senses that a patient’s anxiety is far beyond the ‘normal’ that we all have from time to time, and it is seemingly adversely impacting both their psychological and physical health, it would be reasonable to suggest to the patient that it might be useful to speak with a mental health professional, and if the patient is receptive, to then make a formal consultation or referral,” said Dr. Levine, who was writing group chair of a recent AHA Scientific Statement on mind-heart-body connection.
 

Neuroticism and worry

Several studies have linked anxiety to a greater risk of cardiometabolic disease onset, Dr. Lee and colleagues wrote, but it is unclear if anxious individuals have a steadily worsening risk as they age, or if they have a higher risk in middle age, which stays the same in older age.

To investigate this, they analyzed data from 1561 men who were seen at the VA Boston outpatient clinic and did not have CAD, type 2 diabetes, stroke, or cancer when they enrolled in the Normative Aging Study.

The men had a mean age of 53 years (range, 33-84) in 1975 and were followed until 2015 or until dropout from the study or death.

At baseline, the study participants filled in the Eysenck Personality Inventory, which assesses neuroticism, and also responded to a scale indicating how much they worry about 20 issues (excluding health).

“Neuroticism,” the researchers explained, “is a tendency to perceive experiences as threatening, feel that challenges are uncontrollable, and experience frequent and disproportionately intense negative emotions,” such as fear, anxiety, sadness, and anger, “across many situations.”

“Worry refers to attempts to solve a problem where future outcome is uncertain and potentially positive or negative,” Dr. Lee noted. Although worry can be healthy and lead to constructive solutions, “it may be unhealthy, especially when it becomes uncontrollable and interferes with day-to-day functioning.”

Of note, in 1980, the American Psychiatric Association removed the term neurosis from its diagnostic manual. What was previously called neurosis is included as part of generalized anxiety disorder; GAD also encompasses excessive worry.
 

Cardiometabolic risk from midlife to old age

The men in the current study had on-site physical examinations every 3-5 years.

The researchers calculated the men’s cardiometabolic risk score (from 0 to 7) by assigning 1 point each for the following: systolic blood pressure greater than 130 mm Hg, diastolic blood pressure greater than 85 mm Hg, total cholesterol of at least 240 mg/dL, triglycerides of at least 150 mg/dL, body mass index of at least 30 kg/m2, glucose of at least 100 mg/dL, and erythrocyte sedimentation rate of at least 14 mm/hour.

Alternatively, patients were assigned a point each for taking medication that could affect these markers (except for body mass index).

Overall, on average, at baseline, the men had a cardiometabolic risk score of 2.9. From age 33-65, this score increased to 3.8, and then it did not increase as much later on.

That is, the cardiometabolic risk score increased by 0.8 per decade until age 65, followed by a slower increase of 0.5 per decade.

At all ages, men with higher levels of neuroticism or worry had a higher cardiometabolic risk score

Each additional standard deviation of neuroticism was associated with a 13% increased risk of having six or more of the seven cardiometabolic risk markers during follow-up, after adjusting for age, demographics, and family history of CAD, but the relationship was attenuated after also adjusting for health behaviors (for example, smoking, alcohol consumption, physical activity, and past-year physician visit at baseline).

Similarly, each additional standard deviation of worry was associated with a 10% increased risk of having six or more of the seven cardiometabolic risk markers during follow-up after the same adjustments, and was also no longer significantly different after the same further adjustments.

The research was supported by grants from the National Institutes of Health and a Senior Research Career Scientist Award from the Office of Research and Development, Department of Veterans Affairs. The Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center and is supported by the VA Cooperative Studies Program/Epidemiological Research Centers. The study authors and Dr. Levine disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



A version of this article first appeared on Medscape.com.

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



A version of this article first appeared on Medscape.com.

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



A version of this article first appeared on Medscape.com.