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AFib-related cardiovascular deaths on the rise
PHOENIX, ARIZ. – Cardiovascular deaths and death rates related to atrial fibrillation have risen since 1999, with significant acceleration following 2009, results from a cross-sectional analysis of national data show.
“AFib is the most common arrhythmia disorder in the United States and it is estimated that it will effect more than 12 million Americans by 2030,” Yoshihiro Tanaka, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “The predicted lifetime risk ranges from 25% to 35%, and AFib is associated with an increased risk for heart failure, stroke, and death.”
A recent review reported that declines in total heart disease mortality rates in the United States have plateaued since 2011 (JAMA 2019;322[8]:780-2). However, it is not well understood what factors such as AFib contribute to this rate of plateau. In an effort to quantify U.S. trends in AFib-related CVD death rates, Dr. Tanaka and colleagues conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database during 1999-2017.
Outcomes included age-adjusted mortality per 100,000 based on the 2000 U.S. standard population. The researchers also used joinpoint regression to calculate the average annual percentage change over time and conducted subgroup analyses by race and sex and across two age groups: 35-64 years and 65-84 years.
In all, 522,104 AFib-related CVD deaths were identified during 1999-2017. Dr. Tanaka reported that age-adjusted mortality increased from 16.0 per 100,000 persons in 1999 to 22.2 per 100,000 person in 2017, with an acceleration following an inflection point in 2009. Specifically, the average annual percentage change in AFib-related CVD deaths rose from 0.4% in 2009 to 3.5% in 2017 (P < .001). “These increases were consistent across all race-sex subgroups,” said Dr. Tanaka, of the department of preventive medicine at Northwestern University, Chicago. “Relative increases were also greater in younger compared with older adults, although the absolute number of deaths in younger adults was less.”
The researchers observed that age-adjusted mortality increased across blacks and whites in both age groups, with a more pronounced increase among black and white men. Black men had the highest age-adjusted mortality among persons aged 35-64 (6.5 per 100,000 persons, compared with 4.2 among white men, 2.8 in black women, and 1.6 in white women 1.6 per 100,000). At the same time, white men had the highest age-adjusted mortality rate among those aged 65-84 years (112.5 per 100,000 persons, compared with 87.7 in black men, 77.4 in white women, and 61.3 in black women).
In an interview, one of the session’s moderators, Alvaro Alonso, MD, PhD, said that the study’s reliance on mortality data is a limitation. “You have to be careful with that, because it’s not the whole picture,” said Dr. Alonso, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta. “It could be an underestimation of what is going on. The increase in recent years is probably due to a higher awareness of AFib as a risk factor for stroke; it’s more on the radar. Also, around 2009-2010, we started having new anticoagulants for AFib. It’s getting diagnosed more. When you look at coronary heart disease and stroke, there has been a decrease over time. In mortality and incidence of AFib, we don’t have that. That’s probably because we don’t know very much about what the risk factors for AFib are and how to prevent it.”
Dr. Tanaka said that the cause of increase in AFib-related CVD mortality can be classified into two major categories: a balance between case fatality of AFib and the prevalence of AFib. “The case fatality rate should have decreased over the last years,” he said at the meeting, which was sponsored by the American Heart Association. “In contrast, in the context of the aging of the population, the prevalence of AFib increased over the past years. Contributing factors include increasing awareness of AFib, a change in coding between ICD-9 and ICD-10, and a change in coding practices by physicians.”
Strengths of the study, he said, include its large sample size and the fact that the researchers were able to capture data from all death certificates filed in the United States. Limitations include the fact that the data “do not identify if changes in age-adjusted mortality rates are due to changing incidence or to case fatality rates,” he said. “CDC WONDER does not allow us to explore causes of these descriptive findings, but this would be an important next step.”
Dr. Tanaka reported having no financial disclosures.
SOURCE: Tanaka Y. EPI/Lifestyle 2020, Session 5, Abstract 15.
PHOENIX, ARIZ. – Cardiovascular deaths and death rates related to atrial fibrillation have risen since 1999, with significant acceleration following 2009, results from a cross-sectional analysis of national data show.
“AFib is the most common arrhythmia disorder in the United States and it is estimated that it will effect more than 12 million Americans by 2030,” Yoshihiro Tanaka, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “The predicted lifetime risk ranges from 25% to 35%, and AFib is associated with an increased risk for heart failure, stroke, and death.”
A recent review reported that declines in total heart disease mortality rates in the United States have plateaued since 2011 (JAMA 2019;322[8]:780-2). However, it is not well understood what factors such as AFib contribute to this rate of plateau. In an effort to quantify U.S. trends in AFib-related CVD death rates, Dr. Tanaka and colleagues conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database during 1999-2017.
Outcomes included age-adjusted mortality per 100,000 based on the 2000 U.S. standard population. The researchers also used joinpoint regression to calculate the average annual percentage change over time and conducted subgroup analyses by race and sex and across two age groups: 35-64 years and 65-84 years.
In all, 522,104 AFib-related CVD deaths were identified during 1999-2017. Dr. Tanaka reported that age-adjusted mortality increased from 16.0 per 100,000 persons in 1999 to 22.2 per 100,000 person in 2017, with an acceleration following an inflection point in 2009. Specifically, the average annual percentage change in AFib-related CVD deaths rose from 0.4% in 2009 to 3.5% in 2017 (P < .001). “These increases were consistent across all race-sex subgroups,” said Dr. Tanaka, of the department of preventive medicine at Northwestern University, Chicago. “Relative increases were also greater in younger compared with older adults, although the absolute number of deaths in younger adults was less.”
The researchers observed that age-adjusted mortality increased across blacks and whites in both age groups, with a more pronounced increase among black and white men. Black men had the highest age-adjusted mortality among persons aged 35-64 (6.5 per 100,000 persons, compared with 4.2 among white men, 2.8 in black women, and 1.6 in white women 1.6 per 100,000). At the same time, white men had the highest age-adjusted mortality rate among those aged 65-84 years (112.5 per 100,000 persons, compared with 87.7 in black men, 77.4 in white women, and 61.3 in black women).
In an interview, one of the session’s moderators, Alvaro Alonso, MD, PhD, said that the study’s reliance on mortality data is a limitation. “You have to be careful with that, because it’s not the whole picture,” said Dr. Alonso, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta. “It could be an underestimation of what is going on. The increase in recent years is probably due to a higher awareness of AFib as a risk factor for stroke; it’s more on the radar. Also, around 2009-2010, we started having new anticoagulants for AFib. It’s getting diagnosed more. When you look at coronary heart disease and stroke, there has been a decrease over time. In mortality and incidence of AFib, we don’t have that. That’s probably because we don’t know very much about what the risk factors for AFib are and how to prevent it.”
Dr. Tanaka said that the cause of increase in AFib-related CVD mortality can be classified into two major categories: a balance between case fatality of AFib and the prevalence of AFib. “The case fatality rate should have decreased over the last years,” he said at the meeting, which was sponsored by the American Heart Association. “In contrast, in the context of the aging of the population, the prevalence of AFib increased over the past years. Contributing factors include increasing awareness of AFib, a change in coding between ICD-9 and ICD-10, and a change in coding practices by physicians.”
Strengths of the study, he said, include its large sample size and the fact that the researchers were able to capture data from all death certificates filed in the United States. Limitations include the fact that the data “do not identify if changes in age-adjusted mortality rates are due to changing incidence or to case fatality rates,” he said. “CDC WONDER does not allow us to explore causes of these descriptive findings, but this would be an important next step.”
Dr. Tanaka reported having no financial disclosures.
SOURCE: Tanaka Y. EPI/Lifestyle 2020, Session 5, Abstract 15.
PHOENIX, ARIZ. – Cardiovascular deaths and death rates related to atrial fibrillation have risen since 1999, with significant acceleration following 2009, results from a cross-sectional analysis of national data show.
“AFib is the most common arrhythmia disorder in the United States and it is estimated that it will effect more than 12 million Americans by 2030,” Yoshihiro Tanaka, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “The predicted lifetime risk ranges from 25% to 35%, and AFib is associated with an increased risk for heart failure, stroke, and death.”
A recent review reported that declines in total heart disease mortality rates in the United States have plateaued since 2011 (JAMA 2019;322[8]:780-2). However, it is not well understood what factors such as AFib contribute to this rate of plateau. In an effort to quantify U.S. trends in AFib-related CVD death rates, Dr. Tanaka and colleagues conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database during 1999-2017.
Outcomes included age-adjusted mortality per 100,000 based on the 2000 U.S. standard population. The researchers also used joinpoint regression to calculate the average annual percentage change over time and conducted subgroup analyses by race and sex and across two age groups: 35-64 years and 65-84 years.
In all, 522,104 AFib-related CVD deaths were identified during 1999-2017. Dr. Tanaka reported that age-adjusted mortality increased from 16.0 per 100,000 persons in 1999 to 22.2 per 100,000 person in 2017, with an acceleration following an inflection point in 2009. Specifically, the average annual percentage change in AFib-related CVD deaths rose from 0.4% in 2009 to 3.5% in 2017 (P < .001). “These increases were consistent across all race-sex subgroups,” said Dr. Tanaka, of the department of preventive medicine at Northwestern University, Chicago. “Relative increases were also greater in younger compared with older adults, although the absolute number of deaths in younger adults was less.”
The researchers observed that age-adjusted mortality increased across blacks and whites in both age groups, with a more pronounced increase among black and white men. Black men had the highest age-adjusted mortality among persons aged 35-64 (6.5 per 100,000 persons, compared with 4.2 among white men, 2.8 in black women, and 1.6 in white women 1.6 per 100,000). At the same time, white men had the highest age-adjusted mortality rate among those aged 65-84 years (112.5 per 100,000 persons, compared with 87.7 in black men, 77.4 in white women, and 61.3 in black women).
In an interview, one of the session’s moderators, Alvaro Alonso, MD, PhD, said that the study’s reliance on mortality data is a limitation. “You have to be careful with that, because it’s not the whole picture,” said Dr. Alonso, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta. “It could be an underestimation of what is going on. The increase in recent years is probably due to a higher awareness of AFib as a risk factor for stroke; it’s more on the radar. Also, around 2009-2010, we started having new anticoagulants for AFib. It’s getting diagnosed more. When you look at coronary heart disease and stroke, there has been a decrease over time. In mortality and incidence of AFib, we don’t have that. That’s probably because we don’t know very much about what the risk factors for AFib are and how to prevent it.”
Dr. Tanaka said that the cause of increase in AFib-related CVD mortality can be classified into two major categories: a balance between case fatality of AFib and the prevalence of AFib. “The case fatality rate should have decreased over the last years,” he said at the meeting, which was sponsored by the American Heart Association. “In contrast, in the context of the aging of the population, the prevalence of AFib increased over the past years. Contributing factors include increasing awareness of AFib, a change in coding between ICD-9 and ICD-10, and a change in coding practices by physicians.”
Strengths of the study, he said, include its large sample size and the fact that the researchers were able to capture data from all death certificates filed in the United States. Limitations include the fact that the data “do not identify if changes in age-adjusted mortality rates are due to changing incidence or to case fatality rates,” he said. “CDC WONDER does not allow us to explore causes of these descriptive findings, but this would be an important next step.”
Dr. Tanaka reported having no financial disclosures.
SOURCE: Tanaka Y. EPI/Lifestyle 2020, Session 5, Abstract 15.
REPORTING FROM EPI/LIFESTYLE 2020
Cardiovascular risk varies between black ethnic subgroups
PHOENIX, ARIZ. – Cardiovascular disease risk factors differ significantly between three black ethnic subgroups in the United States, compared with whites, results from a large, long-term cross-sectional study show.
“Race alone does not account for health disparities in CVD risk factors,” lead author Diana Baptiste, DNP, RN, CNE, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “We must consider the environmental, psychosocial, and social factors that may play a larger role in CVD risk among these populations.”
Dr. Baptiste, of the Johns Hopkins University School of Nursing Center for Cardiovascular and Chronic Care in Baltimore, noted that blacks bear a disproportionately greater burden of CVD than that of any other racial group. “Blacks living in the U.S. are not monolithic and include different ethnic subgroups: African Americans, Afro-Caribbeans, defined as black persons who are born in the Caribbean islands, and African immigrants, defined as black persons who are born in Africa,” she said. “It is unclear how Afro-Caribbeans and African immigrants compare to African Americans and whites with regard to CVD risk factors.”
To examine trends in CVD risk factors among the three black ethnic subgroups compared with whites, she and her colleagues performed a cross-sectional analysis of 452,997 adults who participated in the 2010-2018 National Health Interview Survey (NHIS). Of these, 82% were white and 18% were black. Among blacks, 89% were African Americans, 6% were Afro-Caribbeans, and 5% were African immigrants. Outcomes of interest were four self-reported CVD risk factors: hypertension, diabetes, overweight/obesity, and smoking. The researchers used generalized linear models with Poisson distribution to calculate predictive probabilities of CVD risk factors, adjusted for age and sex.
Dr. Baptiste reported that African immigrants represented the youngest subgroup, with an average age of 41 years, compared with an average age of 50 among whites. They were also less likely to have health insurance (76%), compared with Afro-Caribbeans (81%), African Americans (83%), and whites (91%; P < .001). Disparities were observed in the proportion of individuals living below the poverty level. This was led by African Americans (24%), followed by African immigrants (22%), Afro-Caribbeans (18%), and whites (9%).
African immigrants were most likely to be college educated (36%), compared with whites (32%), Afro-Caribbeans (23%), and African Americans (17%; P =.001). In addition, only 33% of African Americans were married, compared with more than 50% of participants in the other ethnic groups.
African Americans had the highest prevalence of hypertension over the time period (from 44% in 2010 to 42% in 2018), while African immigrants had the lowest (from 19% to 17%). African Americans also had the highest prevalence of diabetes over the time period (from 14% to 15%), while African immigrants had the lowest (from 9% to 7%). The prevalence of overweight and obesity was highest among African Americans (from 74% to 76%), while African immigrants had the lowest (63% to 60%). Finally, smoking prevalence was highest in whites and African Americans compared with African immigrants and Afro-Caribbeans, but the prevalence decreased significantly between 2010 and 2018 (P for trend < .001).
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, said that the study’s findings underscore the importance of heterogeneity when counseling patients about CVD risk factors. “Everybody comes from a different cultural background,” said Dr. Brown, a cardiologist and physician scientist at Mayo Clinic, Rochester, Minn. “Cultural backgrounds have an impact on when people eat, how they eat, who they eat with, when they exercise, and whether obesity is valued or not. It’s important to recognize that those cultural underpinnings can contribute to heterogeneity. Other factors – whether they are psychosocial or socioeconomic or environmental – also contribute.”
Strengths of the study, Dr. Baptiste said, included the use of a large, nationally representative dataset. Limitations included its cross-sectional design and the National Health Interview Survey’s reliance on self-reported data. “There were also small sample sizes for African immigrants and Afro-Caribbeans,” she said.
The study was supported by Johns Hopkins University School of Nursing Center for Cardiovascular and Chronic Care. Dr. Baptiste reported having no financial disclosures.
The meeting was sponsored by the American Heart Association.
SOURCE: Baptiste D et al. EPI/Lifestyle 2020, Session 4, Abstract 8.
PHOENIX, ARIZ. – Cardiovascular disease risk factors differ significantly between three black ethnic subgroups in the United States, compared with whites, results from a large, long-term cross-sectional study show.
“Race alone does not account for health disparities in CVD risk factors,” lead author Diana Baptiste, DNP, RN, CNE, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “We must consider the environmental, psychosocial, and social factors that may play a larger role in CVD risk among these populations.”
Dr. Baptiste, of the Johns Hopkins University School of Nursing Center for Cardiovascular and Chronic Care in Baltimore, noted that blacks bear a disproportionately greater burden of CVD than that of any other racial group. “Blacks living in the U.S. are not monolithic and include different ethnic subgroups: African Americans, Afro-Caribbeans, defined as black persons who are born in the Caribbean islands, and African immigrants, defined as black persons who are born in Africa,” she said. “It is unclear how Afro-Caribbeans and African immigrants compare to African Americans and whites with regard to CVD risk factors.”
To examine trends in CVD risk factors among the three black ethnic subgroups compared with whites, she and her colleagues performed a cross-sectional analysis of 452,997 adults who participated in the 2010-2018 National Health Interview Survey (NHIS). Of these, 82% were white and 18% were black. Among blacks, 89% were African Americans, 6% were Afro-Caribbeans, and 5% were African immigrants. Outcomes of interest were four self-reported CVD risk factors: hypertension, diabetes, overweight/obesity, and smoking. The researchers used generalized linear models with Poisson distribution to calculate predictive probabilities of CVD risk factors, adjusted for age and sex.
Dr. Baptiste reported that African immigrants represented the youngest subgroup, with an average age of 41 years, compared with an average age of 50 among whites. They were also less likely to have health insurance (76%), compared with Afro-Caribbeans (81%), African Americans (83%), and whites (91%; P < .001). Disparities were observed in the proportion of individuals living below the poverty level. This was led by African Americans (24%), followed by African immigrants (22%), Afro-Caribbeans (18%), and whites (9%).
African immigrants were most likely to be college educated (36%), compared with whites (32%), Afro-Caribbeans (23%), and African Americans (17%; P =.001). In addition, only 33% of African Americans were married, compared with more than 50% of participants in the other ethnic groups.
African Americans had the highest prevalence of hypertension over the time period (from 44% in 2010 to 42% in 2018), while African immigrants had the lowest (from 19% to 17%). African Americans also had the highest prevalence of diabetes over the time period (from 14% to 15%), while African immigrants had the lowest (from 9% to 7%). The prevalence of overweight and obesity was highest among African Americans (from 74% to 76%), while African immigrants had the lowest (63% to 60%). Finally, smoking prevalence was highest in whites and African Americans compared with African immigrants and Afro-Caribbeans, but the prevalence decreased significantly between 2010 and 2018 (P for trend < .001).
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, said that the study’s findings underscore the importance of heterogeneity when counseling patients about CVD risk factors. “Everybody comes from a different cultural background,” said Dr. Brown, a cardiologist and physician scientist at Mayo Clinic, Rochester, Minn. “Cultural backgrounds have an impact on when people eat, how they eat, who they eat with, when they exercise, and whether obesity is valued or not. It’s important to recognize that those cultural underpinnings can contribute to heterogeneity. Other factors – whether they are psychosocial or socioeconomic or environmental – also contribute.”
Strengths of the study, Dr. Baptiste said, included the use of a large, nationally representative dataset. Limitations included its cross-sectional design and the National Health Interview Survey’s reliance on self-reported data. “There were also small sample sizes for African immigrants and Afro-Caribbeans,” she said.
The study was supported by Johns Hopkins University School of Nursing Center for Cardiovascular and Chronic Care. Dr. Baptiste reported having no financial disclosures.
The meeting was sponsored by the American Heart Association.
SOURCE: Baptiste D et al. EPI/Lifestyle 2020, Session 4, Abstract 8.
PHOENIX, ARIZ. – Cardiovascular disease risk factors differ significantly between three black ethnic subgroups in the United States, compared with whites, results from a large, long-term cross-sectional study show.
“Race alone does not account for health disparities in CVD risk factors,” lead author Diana Baptiste, DNP, RN, CNE, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “We must consider the environmental, psychosocial, and social factors that may play a larger role in CVD risk among these populations.”
Dr. Baptiste, of the Johns Hopkins University School of Nursing Center for Cardiovascular and Chronic Care in Baltimore, noted that blacks bear a disproportionately greater burden of CVD than that of any other racial group. “Blacks living in the U.S. are not monolithic and include different ethnic subgroups: African Americans, Afro-Caribbeans, defined as black persons who are born in the Caribbean islands, and African immigrants, defined as black persons who are born in Africa,” she said. “It is unclear how Afro-Caribbeans and African immigrants compare to African Americans and whites with regard to CVD risk factors.”
To examine trends in CVD risk factors among the three black ethnic subgroups compared with whites, she and her colleagues performed a cross-sectional analysis of 452,997 adults who participated in the 2010-2018 National Health Interview Survey (NHIS). Of these, 82% were white and 18% were black. Among blacks, 89% were African Americans, 6% were Afro-Caribbeans, and 5% were African immigrants. Outcomes of interest were four self-reported CVD risk factors: hypertension, diabetes, overweight/obesity, and smoking. The researchers used generalized linear models with Poisson distribution to calculate predictive probabilities of CVD risk factors, adjusted for age and sex.
Dr. Baptiste reported that African immigrants represented the youngest subgroup, with an average age of 41 years, compared with an average age of 50 among whites. They were also less likely to have health insurance (76%), compared with Afro-Caribbeans (81%), African Americans (83%), and whites (91%; P < .001). Disparities were observed in the proportion of individuals living below the poverty level. This was led by African Americans (24%), followed by African immigrants (22%), Afro-Caribbeans (18%), and whites (9%).
African immigrants were most likely to be college educated (36%), compared with whites (32%), Afro-Caribbeans (23%), and African Americans (17%; P =.001). In addition, only 33% of African Americans were married, compared with more than 50% of participants in the other ethnic groups.
African Americans had the highest prevalence of hypertension over the time period (from 44% in 2010 to 42% in 2018), while African immigrants had the lowest (from 19% to 17%). African Americans also had the highest prevalence of diabetes over the time period (from 14% to 15%), while African immigrants had the lowest (from 9% to 7%). The prevalence of overweight and obesity was highest among African Americans (from 74% to 76%), while African immigrants had the lowest (63% to 60%). Finally, smoking prevalence was highest in whites and African Americans compared with African immigrants and Afro-Caribbeans, but the prevalence decreased significantly between 2010 and 2018 (P for trend < .001).
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, said that the study’s findings underscore the importance of heterogeneity when counseling patients about CVD risk factors. “Everybody comes from a different cultural background,” said Dr. Brown, a cardiologist and physician scientist at Mayo Clinic, Rochester, Minn. “Cultural backgrounds have an impact on when people eat, how they eat, who they eat with, when they exercise, and whether obesity is valued or not. It’s important to recognize that those cultural underpinnings can contribute to heterogeneity. Other factors – whether they are psychosocial or socioeconomic or environmental – also contribute.”
Strengths of the study, Dr. Baptiste said, included the use of a large, nationally representative dataset. Limitations included its cross-sectional design and the National Health Interview Survey’s reliance on self-reported data. “There were also small sample sizes for African immigrants and Afro-Caribbeans,” she said.
The study was supported by Johns Hopkins University School of Nursing Center for Cardiovascular and Chronic Care. Dr. Baptiste reported having no financial disclosures.
The meeting was sponsored by the American Heart Association.
SOURCE: Baptiste D et al. EPI/Lifestyle 2020, Session 4, Abstract 8.
REPORTING FROM EPI/LIFESTYLE 2020
COVID-19 will test medical supply stocks
In a JAMA Live Stream interview, in the United States.
Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.
The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.
“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”
He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”
Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
Stress test on the health care system
Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.
In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”
The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.
Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
Returning to work after COVID-19 infection
Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.
“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.
Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
Higher risk reported in cardiac patients
Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.
Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.
He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
Potential therapies
Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.
Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”
In a JAMA Live Stream interview, in the United States.
Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.
The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.
“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”
He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”
Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
Stress test on the health care system
Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.
In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”
The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.
Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
Returning to work after COVID-19 infection
Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.
“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.
Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
Higher risk reported in cardiac patients
Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.
Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.
He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
Potential therapies
Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.
Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”
In a JAMA Live Stream interview, in the United States.
Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.
The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.
“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”
He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”
Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
Stress test on the health care system
Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.
In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”
The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.
Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
Returning to work after COVID-19 infection
Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.
“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.
Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
Higher risk reported in cardiac patients
Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.
Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.
He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
Potential therapies
Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.
Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”
REPORTING FROM JAMA LIVE STREAM
COVID-19: U.S. cardiology groups reaffirm continued use of RAAS-active drugs
Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.
Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.
Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.
FDA advises stopping SGLT2 inhibitor treatment prior to surgery
The new changes affect canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, and were made because surgery may put patients being treated with SGLT2 inhibitors at a higher risk of ketoacidosis. Canagliflozin, dapagliflozin, and empagliflozin should be discontinued 3 days before scheduled surgery, and ertugliflozin should be stopped at least 4 days before, the agency noted in a press release. Blood glucose should be monitored after drug discontinuation and appropriately managed before surgery.
“The SGLT2 inhibitor may be restarted once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis are resolved,” the agency added.
SGLT2 inhibitors lower blood sugar by causing the kidney to remove sugar from the body through urine. Side effects for the drugs vary, but include urinary tract infections and genital mycotic infection. Patients with severe renal impairment or end-stage renal disease, who are on dialysis treatment, or who have a known hypersensitivity to the medication should not take SGLT2 inhibitors, the FDA said.
The new changes affect canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, and were made because surgery may put patients being treated with SGLT2 inhibitors at a higher risk of ketoacidosis. Canagliflozin, dapagliflozin, and empagliflozin should be discontinued 3 days before scheduled surgery, and ertugliflozin should be stopped at least 4 days before, the agency noted in a press release. Blood glucose should be monitored after drug discontinuation and appropriately managed before surgery.
“The SGLT2 inhibitor may be restarted once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis are resolved,” the agency added.
SGLT2 inhibitors lower blood sugar by causing the kidney to remove sugar from the body through urine. Side effects for the drugs vary, but include urinary tract infections and genital mycotic infection. Patients with severe renal impairment or end-stage renal disease, who are on dialysis treatment, or who have a known hypersensitivity to the medication should not take SGLT2 inhibitors, the FDA said.
The new changes affect canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, and were made because surgery may put patients being treated with SGLT2 inhibitors at a higher risk of ketoacidosis. Canagliflozin, dapagliflozin, and empagliflozin should be discontinued 3 days before scheduled surgery, and ertugliflozin should be stopped at least 4 days before, the agency noted in a press release. Blood glucose should be monitored after drug discontinuation and appropriately managed before surgery.
“The SGLT2 inhibitor may be restarted once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis are resolved,” the agency added.
SGLT2 inhibitors lower blood sugar by causing the kidney to remove sugar from the body through urine. Side effects for the drugs vary, but include urinary tract infections and genital mycotic infection. Patients with severe renal impairment or end-stage renal disease, who are on dialysis treatment, or who have a known hypersensitivity to the medication should not take SGLT2 inhibitors, the FDA said.
African Americans with SLE face increased risk of CVD hospitalizations
PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.
“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”
According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”
In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.
The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).
Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).
Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.
“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”
Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.
SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.
PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.
“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”
According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”
In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.
The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).
Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).
Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.
“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”
Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.
SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.
PHOENIX – African Americans with systemic lupus erythematosus are more likely to experience recurrent hospitalizations for cardiovascular disease, compared with other racial/ethnic groups, results from a single-state registry study found.
“SLE is an autoimmune disease that causes inflammation affecting multiple organ systems including the cardiovascular system,” Meghan Angley, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Therefore, individuals with SLE are at risk for early CVD. African Americans represent the racial group at greatest risk for SLE.”
According to Ms. Angley, with the department of epidemiology at Emory University, Atlanta, white women with SLE have CVD associated mortality 12 years earlier than their non-SLE counterparts, while African American women with SLE have CVD-associated mortality 19 years earlier than their non-SLE counterparts. “We know that recurrent hospitalizations for CVD are associated with mortality,” she said. “These represent potential points of identification of high-risk individuals and also points of interventions.”
In order to study racial disparities across recurrent hospitalizations for cardiovascular disease in an SLE population, Ms. Angley and her colleagues drew from the Georgia Lupus Registry, which is a population-based registry of patients with validated SLE in two Georgia counties. They included all cases diagnosed between 2000 and 2004. The registry was linked to records of all inpatient hospitalizations in Georgia between 2000 and 2013. The researchers used ICD-9 codes to identify hospitalizations for coronary heart disease, peripheral artery disease, cerebrovascular disease, and heart failure and used the Prentice-Williams-Peterson model for recurrent time-to-event analysis. Specifically, they looked at the total time scale from the point of diagnosis to each of the subsequent CVD hospitalizations and truncated the number of hospitalizations at three to maintain stable modeling estimates. The analysis was censored at the time of patient death or at the end of 2013 and adjusted for sex and age at diagnosis.
The sample included 417 African Americans with SLE and 149 non–African Americans with the disease. Most (86%) were female, and the non–African American group was slightly more likely to have been diagnosed with SLE after the age of 45 years, compared with the African American group (36% vs. 30%, respectively).
Ms. Angley and her colleagues found that 24% of African Americans had at least one CVD hospitalization, and 14% had at least two, while 13% of non–African Americans had at least one CVD hospitalization, and 5% had at least two. Among those in the African American group, reasons for hospitalizations were congestive heart failure, (58%), cerebrovascular disease (27%), coronary heart disease (18%), and peripheral artery disease (2%). Among those in the non–African American group, reasons for hospitalizations were congestive heart failure (38%), coronary heart disease (38%), cerebrovascular disease (25%), and peripheral artery disease (6%).
Overall, African American race was associated with recurrent hospitalizations (adjusted hazard ratio, 1.9). In an event-specific stratified analysis, the association between African American race and the hazard of recurrence became even more pronounced with each event (hospitalization 1 aHR, 1.2; hospitalization 2 aHR, 1.5; hospitalization 3 aHR, 1.9). The researchers also observed that African Americans were hospitalized sooner, compared with non–African Americans: a median of 3.68 versus 4.61 years for hospitalization 1, 3.73 years versus 5.98 years for hospitalization 2, and 4.84 years versus 8.14 years for hospitalization 3.
“African Americans with SLE are more likely to experience recurrent hospitalizations for CVD,” Ms. Angley concluded at the meeting, which was sponsored by the American Heart Association. “The events occur sooner after diagnosis than in non–African Americans, suggesting that African Americans may be more vulnerable to the cardiovascular complications of SLE. Our next steps include examining potential reasons for these disparities, such as looking at primary care patterns over time, SLE severity over time, and treatment at CVD hospitalizations.”
In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, called for additional research to determine the reasons for disparities that were observed between African Americans with SLE and their non–African American counterparts. “We need to figure out why and address it,” said Dr. Brown, who is a cardiologist and physician-scientist at Mayo Clinic, Rochester, Minn. “We recognize that social determinants of health, such as insurance, socioeconomic factors, and psychosocial factors, can contribute. We need to figure out the additional steps we need to take in order to close that gap.”
Ms. Angley reported having no disclosures. The study was funded by grants from the Centers for Disease Control and Prevention and by the National Institutes of Health.
SOURCE: Angley M et al. Epi/Lifestyle 2020, Abstract 5.
REPORTING FROM EPI/LIFESTYLE 2020
PARAGON-HF: Optimal systolic pressure in HFpEF is 120-129 mm Hg
A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial.
This finding from the largest-ever randomized, controlled study in heart failure with preserved ejection fraction (HFpEF) strengthens support for current U.S. joint hypertension guidelines, which call for a target SBP less than 130 mm Hg in patients with HFpEF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803), a recommendation based upon weak evidence until now. That’s because the SPRINT trial, the major impetus for adoption of intensive blood pressure control in the current guidelines, excluded patients with symptomatic HF, Scott D. Solomon, MD, and coinvestigators noted in their new analysis. The study was published in the Journal of the American College of Cardiology and had been planned for presentation during the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
The new analysis from PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) also ruled out the SBP-lowering effect of sacubitril/valsartan (Entresto) as the explanation for the combination drug’s demonstrated beneficial impact on outcomes in the subgroup with an SBP of 120-129 mm Hg. That wasn’t actually a surprise. Indeed, the new study had two hypotheses: one, that the relationship between SBP and cardiovascular and renal outcomes in HFpEF would follow a J-shaped curve, and two, that sacubitril/valsartan’s blood pressure–lowering effect would not account for the drug’s outcome benefits in the subset of HFpEF patients with an SBP in the sweet spot of 120-129 mm Hg. Both hypotheses were borne out, noted Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital, both in Boston.
“These data strongly support that additional mechanisms other than blood pressure–lowering account for the benefit. But this is not surprising. The same can be said for most of the therapies that work in heart failure,” he said in an interview.
Take, for example, spironolactone. In TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), another major trial in which Dr. Solomon played a leadership role, the beneficial effect of spironolactone on clinical outcomes also proved unrelated to the drug’s blood pressure–lowering effect.
Other known effects of sacubitril/valsartan, a novel angiotensin receptor–neprilysin inhibitor, or ARNI, might in theory account for the observed clinical benefits in ARNI-treated patients with an on-treatment SBP of 120-129 mm Hg in PARAGON-HF. These include improved left atrial remodeling, an increase in natriuretic peptides, and improved myocardial relaxation. However, the current lack of understanding of the basic mechanistic processes underlying the varied clinical expressions of HFpEF is a major factor contributing to the lack of any proven-effective therapy for this extremely common and costly disorder, according to Dr. Solomon and coinvestigators.
In contrast to HFpEF, for which to date there is no proven treatment, heart failure with reduced ejection fraction sacubitril/valsartan has a class I recommendation on the strength of its performance in significantly reducing cardiovascular deaths and heart failure hospitalizations in the PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371:993-1004).
PARAGON-HF included 4,822 patients with symptomatic HFpEF who were randomized to sacubitril/valsartan at 97/103 mg b.i.d. or valsartan at 160 mg b.i.d. As previously reported (N Engl J Med. 2019 Oct 24;381[17]:1609-20), at an average follow-up of 35 months, the primary outcome – a composite of total hospitalizations for heart failure and cardiovascular death – occurred at a rate of 12.8 events per 100 patient-years in the sacubitril/valsartan group and 14.6 per 100 patient-years in the valsartan arm, for a 13% relative risk reduction that narrowly missed statistical significance (P = .059).
However, sacubitril/valsartan showed significant benefit on some prespecified secondary endpoints, including worsening renal function, change in New York Heart Association class, and quality of life. Women, who notably accounted for 52% of study participants, appeared to benefit from sacubitril/valsartan more than men as evidenced by their 27% relative risk reduction in the primary endpoint. Also, in the roughly half of PARAGON-HF participants with a baseline left ventricular ejection fraction of 45%-57%, treatment with sacubitril/valsartan resulted in a statistically significant 22% relative risk reduction in the primary endpoint, compared with valsartan alone.
SBP and cardiovascular outcomes in HFpEF
In the new analysis, Dr. Solomon and coworkers examined outcomes based on baseline and mean achieved SBP quartiles regardless of treatment arm. In an unadjusted analysis, the primary composite endpoint occurred at a rate of 15.2 events/100 patient-years in HFpEF patients with an achieved SBP below 120 mm Hg, 11.4/100 patient-years at 120-129 mm Hg, 12.2/100 patient-years at 130-139 mm Hg, and 15.6/100 patient-years at 140 mm Hg or more. Further, in a multivariate regression analysis extensively adjusted for atrial fibrillation, sex, race, and numerous other potential confounders, the group with an achieved SBP of 120-129 mm Hg continued to fare best. The adjusted risks for the primary endpoint were 11% and 21% higher in patients in the first and third quartiles of achieved SBP, compared with those at 120-129 mm Hg, although neither trend reached statistical significance. But patients in the top quartile, with an achieved SBP of 140 mm Hg or more, had a highly significant 56% increase in risk, compared with patients in the second-lowest SBP quartile.
Change in blood pressure from baseline to week 48 had no impact on quality of life or high-sensitivity troponin T. However, each 10–mm Hg lowering of SBP was associated with a modest 2.1% reduction in log-transformed N-terminal of the prohormone brain natriuretic peptide.
Sacubitril/valsartan reduced SBP by an average of 5.2 mm Hg more than valsartan alone at 4 weeks regardless of baseline SBP. And the combo drug had a significantly greater SBP-lowering effect in women than men, by a margin of 6.3 mm Hg versus 4.0 mm Hg. But a Cox regression analysis showed that in women, as in the study population as a whole, sacubitril/valsartan’s SBP-lowering effects didn’t account for the drug’s impact on outcomes.
In an editorial accompanying publication of the new PARAGON-HF blood pressure analysis (J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.024), Hector O. Ventura, MD, and colleagues at the Ochsner Clinic in New Orleans observed that the study results “lend some credence to the prognostic relationship of blood pressure in HFpEF, but whether they should serve as a therapeutic target or are merely a prognostic surrogate determined by other pathogenic factors, such as vascular ventricular uncoupling or aortic stiffness on one hand when blood pressure is greater than 140 mm Hg, or a reduced cardiac performance indicated by reduced blood pressure to less than 120 mm Hg, remains uncertain.”
“What is certain, however, is that the relationship and contributions of hypertension in manifest HFpEF are complex, multifactorial and likely go well beyond a simplistic framework of hemodynamic influences,” they added.
Dr. Solomon has received research grants from and serves as a consultant to Novartis, which funded PARAGON-HF, and has similar financial relationships with more than a dozen other pharmaceutical companies. Dr. Ventura reported having no relevant financial interests.
SOURCE: Solomon SD et al. J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.009.
A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial.
This finding from the largest-ever randomized, controlled study in heart failure with preserved ejection fraction (HFpEF) strengthens support for current U.S. joint hypertension guidelines, which call for a target SBP less than 130 mm Hg in patients with HFpEF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803), a recommendation based upon weak evidence until now. That’s because the SPRINT trial, the major impetus for adoption of intensive blood pressure control in the current guidelines, excluded patients with symptomatic HF, Scott D. Solomon, MD, and coinvestigators noted in their new analysis. The study was published in the Journal of the American College of Cardiology and had been planned for presentation during the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
The new analysis from PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) also ruled out the SBP-lowering effect of sacubitril/valsartan (Entresto) as the explanation for the combination drug’s demonstrated beneficial impact on outcomes in the subgroup with an SBP of 120-129 mm Hg. That wasn’t actually a surprise. Indeed, the new study had two hypotheses: one, that the relationship between SBP and cardiovascular and renal outcomes in HFpEF would follow a J-shaped curve, and two, that sacubitril/valsartan’s blood pressure–lowering effect would not account for the drug’s outcome benefits in the subset of HFpEF patients with an SBP in the sweet spot of 120-129 mm Hg. Both hypotheses were borne out, noted Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital, both in Boston.
“These data strongly support that additional mechanisms other than blood pressure–lowering account for the benefit. But this is not surprising. The same can be said for most of the therapies that work in heart failure,” he said in an interview.
Take, for example, spironolactone. In TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), another major trial in which Dr. Solomon played a leadership role, the beneficial effect of spironolactone on clinical outcomes also proved unrelated to the drug’s blood pressure–lowering effect.
Other known effects of sacubitril/valsartan, a novel angiotensin receptor–neprilysin inhibitor, or ARNI, might in theory account for the observed clinical benefits in ARNI-treated patients with an on-treatment SBP of 120-129 mm Hg in PARAGON-HF. These include improved left atrial remodeling, an increase in natriuretic peptides, and improved myocardial relaxation. However, the current lack of understanding of the basic mechanistic processes underlying the varied clinical expressions of HFpEF is a major factor contributing to the lack of any proven-effective therapy for this extremely common and costly disorder, according to Dr. Solomon and coinvestigators.
In contrast to HFpEF, for which to date there is no proven treatment, heart failure with reduced ejection fraction sacubitril/valsartan has a class I recommendation on the strength of its performance in significantly reducing cardiovascular deaths and heart failure hospitalizations in the PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371:993-1004).
PARAGON-HF included 4,822 patients with symptomatic HFpEF who were randomized to sacubitril/valsartan at 97/103 mg b.i.d. or valsartan at 160 mg b.i.d. As previously reported (N Engl J Med. 2019 Oct 24;381[17]:1609-20), at an average follow-up of 35 months, the primary outcome – a composite of total hospitalizations for heart failure and cardiovascular death – occurred at a rate of 12.8 events per 100 patient-years in the sacubitril/valsartan group and 14.6 per 100 patient-years in the valsartan arm, for a 13% relative risk reduction that narrowly missed statistical significance (P = .059).
However, sacubitril/valsartan showed significant benefit on some prespecified secondary endpoints, including worsening renal function, change in New York Heart Association class, and quality of life. Women, who notably accounted for 52% of study participants, appeared to benefit from sacubitril/valsartan more than men as evidenced by their 27% relative risk reduction in the primary endpoint. Also, in the roughly half of PARAGON-HF participants with a baseline left ventricular ejection fraction of 45%-57%, treatment with sacubitril/valsartan resulted in a statistically significant 22% relative risk reduction in the primary endpoint, compared with valsartan alone.
SBP and cardiovascular outcomes in HFpEF
In the new analysis, Dr. Solomon and coworkers examined outcomes based on baseline and mean achieved SBP quartiles regardless of treatment arm. In an unadjusted analysis, the primary composite endpoint occurred at a rate of 15.2 events/100 patient-years in HFpEF patients with an achieved SBP below 120 mm Hg, 11.4/100 patient-years at 120-129 mm Hg, 12.2/100 patient-years at 130-139 mm Hg, and 15.6/100 patient-years at 140 mm Hg or more. Further, in a multivariate regression analysis extensively adjusted for atrial fibrillation, sex, race, and numerous other potential confounders, the group with an achieved SBP of 120-129 mm Hg continued to fare best. The adjusted risks for the primary endpoint were 11% and 21% higher in patients in the first and third quartiles of achieved SBP, compared with those at 120-129 mm Hg, although neither trend reached statistical significance. But patients in the top quartile, with an achieved SBP of 140 mm Hg or more, had a highly significant 56% increase in risk, compared with patients in the second-lowest SBP quartile.
Change in blood pressure from baseline to week 48 had no impact on quality of life or high-sensitivity troponin T. However, each 10–mm Hg lowering of SBP was associated with a modest 2.1% reduction in log-transformed N-terminal of the prohormone brain natriuretic peptide.
Sacubitril/valsartan reduced SBP by an average of 5.2 mm Hg more than valsartan alone at 4 weeks regardless of baseline SBP. And the combo drug had a significantly greater SBP-lowering effect in women than men, by a margin of 6.3 mm Hg versus 4.0 mm Hg. But a Cox regression analysis showed that in women, as in the study population as a whole, sacubitril/valsartan’s SBP-lowering effects didn’t account for the drug’s impact on outcomes.
In an editorial accompanying publication of the new PARAGON-HF blood pressure analysis (J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.024), Hector O. Ventura, MD, and colleagues at the Ochsner Clinic in New Orleans observed that the study results “lend some credence to the prognostic relationship of blood pressure in HFpEF, but whether they should serve as a therapeutic target or are merely a prognostic surrogate determined by other pathogenic factors, such as vascular ventricular uncoupling or aortic stiffness on one hand when blood pressure is greater than 140 mm Hg, or a reduced cardiac performance indicated by reduced blood pressure to less than 120 mm Hg, remains uncertain.”
“What is certain, however, is that the relationship and contributions of hypertension in manifest HFpEF are complex, multifactorial and likely go well beyond a simplistic framework of hemodynamic influences,” they added.
Dr. Solomon has received research grants from and serves as a consultant to Novartis, which funded PARAGON-HF, and has similar financial relationships with more than a dozen other pharmaceutical companies. Dr. Ventura reported having no relevant financial interests.
SOURCE: Solomon SD et al. J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.009.
A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial.
This finding from the largest-ever randomized, controlled study in heart failure with preserved ejection fraction (HFpEF) strengthens support for current U.S. joint hypertension guidelines, which call for a target SBP less than 130 mm Hg in patients with HFpEF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803), a recommendation based upon weak evidence until now. That’s because the SPRINT trial, the major impetus for adoption of intensive blood pressure control in the current guidelines, excluded patients with symptomatic HF, Scott D. Solomon, MD, and coinvestigators noted in their new analysis. The study was published in the Journal of the American College of Cardiology and had been planned for presentation during the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
The new analysis from PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) also ruled out the SBP-lowering effect of sacubitril/valsartan (Entresto) as the explanation for the combination drug’s demonstrated beneficial impact on outcomes in the subgroup with an SBP of 120-129 mm Hg. That wasn’t actually a surprise. Indeed, the new study had two hypotheses: one, that the relationship between SBP and cardiovascular and renal outcomes in HFpEF would follow a J-shaped curve, and two, that sacubitril/valsartan’s blood pressure–lowering effect would not account for the drug’s outcome benefits in the subset of HFpEF patients with an SBP in the sweet spot of 120-129 mm Hg. Both hypotheses were borne out, noted Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital, both in Boston.
“These data strongly support that additional mechanisms other than blood pressure–lowering account for the benefit. But this is not surprising. The same can be said for most of the therapies that work in heart failure,” he said in an interview.
Take, for example, spironolactone. In TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), another major trial in which Dr. Solomon played a leadership role, the beneficial effect of spironolactone on clinical outcomes also proved unrelated to the drug’s blood pressure–lowering effect.
Other known effects of sacubitril/valsartan, a novel angiotensin receptor–neprilysin inhibitor, or ARNI, might in theory account for the observed clinical benefits in ARNI-treated patients with an on-treatment SBP of 120-129 mm Hg in PARAGON-HF. These include improved left atrial remodeling, an increase in natriuretic peptides, and improved myocardial relaxation. However, the current lack of understanding of the basic mechanistic processes underlying the varied clinical expressions of HFpEF is a major factor contributing to the lack of any proven-effective therapy for this extremely common and costly disorder, according to Dr. Solomon and coinvestigators.
In contrast to HFpEF, for which to date there is no proven treatment, heart failure with reduced ejection fraction sacubitril/valsartan has a class I recommendation on the strength of its performance in significantly reducing cardiovascular deaths and heart failure hospitalizations in the PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371:993-1004).
PARAGON-HF included 4,822 patients with symptomatic HFpEF who were randomized to sacubitril/valsartan at 97/103 mg b.i.d. or valsartan at 160 mg b.i.d. As previously reported (N Engl J Med. 2019 Oct 24;381[17]:1609-20), at an average follow-up of 35 months, the primary outcome – a composite of total hospitalizations for heart failure and cardiovascular death – occurred at a rate of 12.8 events per 100 patient-years in the sacubitril/valsartan group and 14.6 per 100 patient-years in the valsartan arm, for a 13% relative risk reduction that narrowly missed statistical significance (P = .059).
However, sacubitril/valsartan showed significant benefit on some prespecified secondary endpoints, including worsening renal function, change in New York Heart Association class, and quality of life. Women, who notably accounted for 52% of study participants, appeared to benefit from sacubitril/valsartan more than men as evidenced by their 27% relative risk reduction in the primary endpoint. Also, in the roughly half of PARAGON-HF participants with a baseline left ventricular ejection fraction of 45%-57%, treatment with sacubitril/valsartan resulted in a statistically significant 22% relative risk reduction in the primary endpoint, compared with valsartan alone.
SBP and cardiovascular outcomes in HFpEF
In the new analysis, Dr. Solomon and coworkers examined outcomes based on baseline and mean achieved SBP quartiles regardless of treatment arm. In an unadjusted analysis, the primary composite endpoint occurred at a rate of 15.2 events/100 patient-years in HFpEF patients with an achieved SBP below 120 mm Hg, 11.4/100 patient-years at 120-129 mm Hg, 12.2/100 patient-years at 130-139 mm Hg, and 15.6/100 patient-years at 140 mm Hg or more. Further, in a multivariate regression analysis extensively adjusted for atrial fibrillation, sex, race, and numerous other potential confounders, the group with an achieved SBP of 120-129 mm Hg continued to fare best. The adjusted risks for the primary endpoint were 11% and 21% higher in patients in the first and third quartiles of achieved SBP, compared with those at 120-129 mm Hg, although neither trend reached statistical significance. But patients in the top quartile, with an achieved SBP of 140 mm Hg or more, had a highly significant 56% increase in risk, compared with patients in the second-lowest SBP quartile.
Change in blood pressure from baseline to week 48 had no impact on quality of life or high-sensitivity troponin T. However, each 10–mm Hg lowering of SBP was associated with a modest 2.1% reduction in log-transformed N-terminal of the prohormone brain natriuretic peptide.
Sacubitril/valsartan reduced SBP by an average of 5.2 mm Hg more than valsartan alone at 4 weeks regardless of baseline SBP. And the combo drug had a significantly greater SBP-lowering effect in women than men, by a margin of 6.3 mm Hg versus 4.0 mm Hg. But a Cox regression analysis showed that in women, as in the study population as a whole, sacubitril/valsartan’s SBP-lowering effects didn’t account for the drug’s impact on outcomes.
In an editorial accompanying publication of the new PARAGON-HF blood pressure analysis (J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.024), Hector O. Ventura, MD, and colleagues at the Ochsner Clinic in New Orleans observed that the study results “lend some credence to the prognostic relationship of blood pressure in HFpEF, but whether they should serve as a therapeutic target or are merely a prognostic surrogate determined by other pathogenic factors, such as vascular ventricular uncoupling or aortic stiffness on one hand when blood pressure is greater than 140 mm Hg, or a reduced cardiac performance indicated by reduced blood pressure to less than 120 mm Hg, remains uncertain.”
“What is certain, however, is that the relationship and contributions of hypertension in manifest HFpEF are complex, multifactorial and likely go well beyond a simplistic framework of hemodynamic influences,” they added.
Dr. Solomon has received research grants from and serves as a consultant to Novartis, which funded PARAGON-HF, and has similar financial relationships with more than a dozen other pharmaceutical companies. Dr. Ventura reported having no relevant financial interests.
SOURCE: Solomon SD et al. J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.009.
FROM ACC 2020
ICH survival lags in the community setting
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
REPORTING FROM ISC 2020
High CV event risk seen in SLE patients with ACC/AHA-defined hypertension
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
FROM ANNALS OF THE RHEUMATIC DISEASES
Childhood CV health tied to reduced risk later in life
Two observational studies link better cardiovascular health (CVH) in childhood and midlife to reduced CV mortality and subclinical atherosclerosis in later life. Though many studies have examined CVH and CV mortality in later life, the two studies, published in JAMA Cardiology, examine longitudinal CVH and could inform lifestyle modification.
Together, the studies lend support to the American Heart Association 2010 Strategic Initiative, which put an emphasis on health promotion in children rather than CV disease prevention, Erica Spatz, MD, of Yale University, New Haven, Conn., wrote in an accompanying editorial.
Dr. Spatz pointed out that CV disease prevention can be a tough sell, especially in younger patients for whom the threat of heart disease is distant. These studies and others like them could capture evolving risk factors through patients’ lives, and connect them to current lifestyle and experiences. Such data could overcome barriers to behavioral change and lead to more personalized interventions, she wrote.
Framingham Offspring Study
One study, led by Vanessa Xanthakis, PhD, of Boston University, examined the relationship between the length of time during midlife spent in ideal CVH and various CV disease and mortality outcomes at the final examination.
The prospective study included 1,445 participants (mean age 60 years, 52% women) from a Framingham Heart Study Offspring investigation based in Massachusetts. The subjects had completed seven examinations. The current study ranged from 1991 to 2015, and encompassed the fifth, sixth, and seventh examinations. Researchers calculated CVH scores based on resting blood pressure, height, weight, total cholesterol level, fasting blood glucose level, smoking status, diet, and physical activity.
At the seventh examination, 39% of participants had poor CVH scores and 54% had intermediate scores. For each 5-year period of intermediate or ideal CVH (compared with poor) measured in previous examinations, during the follow-up period after the seventh examination, there was an associated reduction in risk for adverse outcomes including incident hypertension (hazard ratio, 0.67; 95% confidence interval, 056-0.80), diabetes (HR, 0.73; 95% CI, 0.57-0.93), chronic kidney disease (HR, 0.75; 95% CI, 0.63-0.89), CV disease (HR, 0.73; 95% CI, 0.63-0.85), and all-cause mortality (HR, 0.86; 95% CI, 0.76-0.97).
“Our results indicated that living longer in adulthood with better CVH may be potentially beneficial regardless of age because we did not observe statistically significant effect modification by age of the associations between duration in a given CVH score category and any outcome. Overall, our findings support the importance of promoting healthy behaviors throughout the life course,” the authors wrote.
The study was limited by several factors. Diet and physical activity were self-reported, and about half of participants were excluded after missing an examination, which could introduce bias.
International cohort study
The second study analyzed data from 9,388 individuals in five prospective cohorts in the United States and Finland. During 1973-2015, it tracked participants from childhood through middle age (age 8-55 years), linking CVH measures to subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT) in middle age. Led by Norrina Allen, PhD, of the Northwestern University, Chicago, the researchers measured body mass index, total cholesterol level, blood pressure, glucose level, diet, physical activity, and smoking status during a minimum of three examinations. Based on those data, they classified participants as having ideal, intermediate, or poor CVH.
The researchers grouped the participants into five CVH trajectories: High-late decline, which started with high CVH scores at age 8 and maintained them through early adulthood (16%); high-moderate decline (high early scores, moderate decline; 26%); high-early decline (high early scores, early-life decline; 32%); intermediate-late decline (intermediate initial scores, late decline; 16%); and intermediate-early decline (10%). CVH stratification began early: At age 8, 25% of individuals had intermediate CVH scores.
After adjustment for demographics and baseline smoking, diet, and physical activity, the high-late decline CVH group had the smallest mean cIMT value (0.64 mm; 95 % CI, 0.63-0.65 mm), while the intermediate-early decline group, which had the poorest CVH, had the largest (0.72 mm; 95% CI, 0.69-0.76 mm; P less than .001). The relationship was the same even after adjustment for baseline or proximal CVH scores, showing that the trajectory of CVH scores was driving the measure of subclinical atherosclerosis.
“Although it remains important to provide treatment to individuals with elevated risk factor levels, the most effective way to reduce the burden of future CV disease may be to prevent the development of those CV disease risk factors, an approach termed primordial prevention. There is a large body of literature showing effective interventions that may help individuals maintain ideal CV health. Our findings suggest that these interventions are critical and should be implemented early in life to prevent the loss of CVH and future CV [disease] development,” the authors wrote.
The study’s limitations include the fact that analyzed cohorts were drawn from studies with varying protocols and CVH measurement methods. It is also limited by its observational nature.
The two studies were funded by a range of nonindustry sources.
SOURCES: Allen N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0140; Corlin N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109.
Two observational studies link better cardiovascular health (CVH) in childhood and midlife to reduced CV mortality and subclinical atherosclerosis in later life. Though many studies have examined CVH and CV mortality in later life, the two studies, published in JAMA Cardiology, examine longitudinal CVH and could inform lifestyle modification.
Together, the studies lend support to the American Heart Association 2010 Strategic Initiative, which put an emphasis on health promotion in children rather than CV disease prevention, Erica Spatz, MD, of Yale University, New Haven, Conn., wrote in an accompanying editorial.
Dr. Spatz pointed out that CV disease prevention can be a tough sell, especially in younger patients for whom the threat of heart disease is distant. These studies and others like them could capture evolving risk factors through patients’ lives, and connect them to current lifestyle and experiences. Such data could overcome barriers to behavioral change and lead to more personalized interventions, she wrote.
Framingham Offspring Study
One study, led by Vanessa Xanthakis, PhD, of Boston University, examined the relationship between the length of time during midlife spent in ideal CVH and various CV disease and mortality outcomes at the final examination.
The prospective study included 1,445 participants (mean age 60 years, 52% women) from a Framingham Heart Study Offspring investigation based in Massachusetts. The subjects had completed seven examinations. The current study ranged from 1991 to 2015, and encompassed the fifth, sixth, and seventh examinations. Researchers calculated CVH scores based on resting blood pressure, height, weight, total cholesterol level, fasting blood glucose level, smoking status, diet, and physical activity.
At the seventh examination, 39% of participants had poor CVH scores and 54% had intermediate scores. For each 5-year period of intermediate or ideal CVH (compared with poor) measured in previous examinations, during the follow-up period after the seventh examination, there was an associated reduction in risk for adverse outcomes including incident hypertension (hazard ratio, 0.67; 95% confidence interval, 056-0.80), diabetes (HR, 0.73; 95% CI, 0.57-0.93), chronic kidney disease (HR, 0.75; 95% CI, 0.63-0.89), CV disease (HR, 0.73; 95% CI, 0.63-0.85), and all-cause mortality (HR, 0.86; 95% CI, 0.76-0.97).
“Our results indicated that living longer in adulthood with better CVH may be potentially beneficial regardless of age because we did not observe statistically significant effect modification by age of the associations between duration in a given CVH score category and any outcome. Overall, our findings support the importance of promoting healthy behaviors throughout the life course,” the authors wrote.
The study was limited by several factors. Diet and physical activity were self-reported, and about half of participants were excluded after missing an examination, which could introduce bias.
International cohort study
The second study analyzed data from 9,388 individuals in five prospective cohorts in the United States and Finland. During 1973-2015, it tracked participants from childhood through middle age (age 8-55 years), linking CVH measures to subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT) in middle age. Led by Norrina Allen, PhD, of the Northwestern University, Chicago, the researchers measured body mass index, total cholesterol level, blood pressure, glucose level, diet, physical activity, and smoking status during a minimum of three examinations. Based on those data, they classified participants as having ideal, intermediate, or poor CVH.
The researchers grouped the participants into five CVH trajectories: High-late decline, which started with high CVH scores at age 8 and maintained them through early adulthood (16%); high-moderate decline (high early scores, moderate decline; 26%); high-early decline (high early scores, early-life decline; 32%); intermediate-late decline (intermediate initial scores, late decline; 16%); and intermediate-early decline (10%). CVH stratification began early: At age 8, 25% of individuals had intermediate CVH scores.
After adjustment for demographics and baseline smoking, diet, and physical activity, the high-late decline CVH group had the smallest mean cIMT value (0.64 mm; 95 % CI, 0.63-0.65 mm), while the intermediate-early decline group, which had the poorest CVH, had the largest (0.72 mm; 95% CI, 0.69-0.76 mm; P less than .001). The relationship was the same even after adjustment for baseline or proximal CVH scores, showing that the trajectory of CVH scores was driving the measure of subclinical atherosclerosis.
“Although it remains important to provide treatment to individuals with elevated risk factor levels, the most effective way to reduce the burden of future CV disease may be to prevent the development of those CV disease risk factors, an approach termed primordial prevention. There is a large body of literature showing effective interventions that may help individuals maintain ideal CV health. Our findings suggest that these interventions are critical and should be implemented early in life to prevent the loss of CVH and future CV [disease] development,” the authors wrote.
The study’s limitations include the fact that analyzed cohorts were drawn from studies with varying protocols and CVH measurement methods. It is also limited by its observational nature.
The two studies were funded by a range of nonindustry sources.
SOURCES: Allen N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0140; Corlin N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109.
Two observational studies link better cardiovascular health (CVH) in childhood and midlife to reduced CV mortality and subclinical atherosclerosis in later life. Though many studies have examined CVH and CV mortality in later life, the two studies, published in JAMA Cardiology, examine longitudinal CVH and could inform lifestyle modification.
Together, the studies lend support to the American Heart Association 2010 Strategic Initiative, which put an emphasis on health promotion in children rather than CV disease prevention, Erica Spatz, MD, of Yale University, New Haven, Conn., wrote in an accompanying editorial.
Dr. Spatz pointed out that CV disease prevention can be a tough sell, especially in younger patients for whom the threat of heart disease is distant. These studies and others like them could capture evolving risk factors through patients’ lives, and connect them to current lifestyle and experiences. Such data could overcome barriers to behavioral change and lead to more personalized interventions, she wrote.
Framingham Offspring Study
One study, led by Vanessa Xanthakis, PhD, of Boston University, examined the relationship between the length of time during midlife spent in ideal CVH and various CV disease and mortality outcomes at the final examination.
The prospective study included 1,445 participants (mean age 60 years, 52% women) from a Framingham Heart Study Offspring investigation based in Massachusetts. The subjects had completed seven examinations. The current study ranged from 1991 to 2015, and encompassed the fifth, sixth, and seventh examinations. Researchers calculated CVH scores based on resting blood pressure, height, weight, total cholesterol level, fasting blood glucose level, smoking status, diet, and physical activity.
At the seventh examination, 39% of participants had poor CVH scores and 54% had intermediate scores. For each 5-year period of intermediate or ideal CVH (compared with poor) measured in previous examinations, during the follow-up period after the seventh examination, there was an associated reduction in risk for adverse outcomes including incident hypertension (hazard ratio, 0.67; 95% confidence interval, 056-0.80), diabetes (HR, 0.73; 95% CI, 0.57-0.93), chronic kidney disease (HR, 0.75; 95% CI, 0.63-0.89), CV disease (HR, 0.73; 95% CI, 0.63-0.85), and all-cause mortality (HR, 0.86; 95% CI, 0.76-0.97).
“Our results indicated that living longer in adulthood with better CVH may be potentially beneficial regardless of age because we did not observe statistically significant effect modification by age of the associations between duration in a given CVH score category and any outcome. Overall, our findings support the importance of promoting healthy behaviors throughout the life course,” the authors wrote.
The study was limited by several factors. Diet and physical activity were self-reported, and about half of participants were excluded after missing an examination, which could introduce bias.
International cohort study
The second study analyzed data from 9,388 individuals in five prospective cohorts in the United States and Finland. During 1973-2015, it tracked participants from childhood through middle age (age 8-55 years), linking CVH measures to subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT) in middle age. Led by Norrina Allen, PhD, of the Northwestern University, Chicago, the researchers measured body mass index, total cholesterol level, blood pressure, glucose level, diet, physical activity, and smoking status during a minimum of three examinations. Based on those data, they classified participants as having ideal, intermediate, or poor CVH.
The researchers grouped the participants into five CVH trajectories: High-late decline, which started with high CVH scores at age 8 and maintained them through early adulthood (16%); high-moderate decline (high early scores, moderate decline; 26%); high-early decline (high early scores, early-life decline; 32%); intermediate-late decline (intermediate initial scores, late decline; 16%); and intermediate-early decline (10%). CVH stratification began early: At age 8, 25% of individuals had intermediate CVH scores.
After adjustment for demographics and baseline smoking, diet, and physical activity, the high-late decline CVH group had the smallest mean cIMT value (0.64 mm; 95 % CI, 0.63-0.65 mm), while the intermediate-early decline group, which had the poorest CVH, had the largest (0.72 mm; 95% CI, 0.69-0.76 mm; P less than .001). The relationship was the same even after adjustment for baseline or proximal CVH scores, showing that the trajectory of CVH scores was driving the measure of subclinical atherosclerosis.
“Although it remains important to provide treatment to individuals with elevated risk factor levels, the most effective way to reduce the burden of future CV disease may be to prevent the development of those CV disease risk factors, an approach termed primordial prevention. There is a large body of literature showing effective interventions that may help individuals maintain ideal CV health. Our findings suggest that these interventions are critical and should be implemented early in life to prevent the loss of CVH and future CV [disease] development,” the authors wrote.
The study’s limitations include the fact that analyzed cohorts were drawn from studies with varying protocols and CVH measurement methods. It is also limited by its observational nature.
The two studies were funded by a range of nonindustry sources.
SOURCES: Allen N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0140; Corlin N et al. JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109.
FROM JAMA CARDIOLOGY