Cardiology

Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.

The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing postpancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.

“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda (Calif.) University, told this news organization.

iStock/ThinkStock

“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Steady use mattered, not dose

Patients with acute pancreatitis face at least a twofold increased risk of developing postpancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of postpancreatitis diabetes.

In a collaborative study with several other universities, Dr. Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 and 2020.

They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9,048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.

With a median follow-up of 3.5 years, the 5-year cumulative incidence of postpancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing postpancreatitis diabetes, compared with nonusers. Irregular statin users had a 15% lower risk of postpancreatitis diabetes.

In addition, the 5-year cumulative incidence of insulin-dependent postpancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.

Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.

Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.

“We were pleasantly surprised by the variety of findings,” Dr. Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
 

Ongoing studies

The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, postpancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with postpancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.

In fact, postpancreatitis diabetes is thought to be driven by chronic low-grade inflammation attributable to interleukin-6 and tumor necrosis factor–alpha. Statins have been shown to reduce tumor necrosis factor–alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.

The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.

In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.

“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Dr. Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”

The Type 1 Diabetes in Acute Pancreatitis Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.

“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told this news organization.

Dr. Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.

“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”

The study didn’t report funding support. Dr. Thiruvengadam and Dr. Forsmark report no relevant financial relationships.

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

Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.

The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing postpancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.

“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda (Calif.) University, told this news organization.

iStock/ThinkStock

“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Steady use mattered, not dose

Patients with acute pancreatitis face at least a twofold increased risk of developing postpancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of postpancreatitis diabetes.

In a collaborative study with several other universities, Dr. Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 and 2020.

They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9,048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.

With a median follow-up of 3.5 years, the 5-year cumulative incidence of postpancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing postpancreatitis diabetes, compared with nonusers. Irregular statin users had a 15% lower risk of postpancreatitis diabetes.

In addition, the 5-year cumulative incidence of insulin-dependent postpancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.

Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.

Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.

“We were pleasantly surprised by the variety of findings,” Dr. Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
 

Ongoing studies

The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, postpancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with postpancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.

In fact, postpancreatitis diabetes is thought to be driven by chronic low-grade inflammation attributable to interleukin-6 and tumor necrosis factor–alpha. Statins have been shown to reduce tumor necrosis factor–alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.

The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.

In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.

“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Dr. Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”

The Type 1 Diabetes in Acute Pancreatitis Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.

“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told this news organization.

Dr. Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.

“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”

The study didn’t report funding support. Dr. Thiruvengadam and Dr. Forsmark report no relevant financial relationships.

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

Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.

The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing postpancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.

“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda (Calif.) University, told this news organization.

iStock/ThinkStock

“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Steady use mattered, not dose

Patients with acute pancreatitis face at least a twofold increased risk of developing postpancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of postpancreatitis diabetes.

In a collaborative study with several other universities, Dr. Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 and 2020.

They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9,048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.

With a median follow-up of 3.5 years, the 5-year cumulative incidence of postpancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing postpancreatitis diabetes, compared with nonusers. Irregular statin users had a 15% lower risk of postpancreatitis diabetes.

In addition, the 5-year cumulative incidence of insulin-dependent postpancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.

Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.

Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.

“We were pleasantly surprised by the variety of findings,” Dr. Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
 

Ongoing studies

The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, postpancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with postpancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.

In fact, postpancreatitis diabetes is thought to be driven by chronic low-grade inflammation attributable to interleukin-6 and tumor necrosis factor–alpha. Statins have been shown to reduce tumor necrosis factor–alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.

The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.

In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.

“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Dr. Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”

The Type 1 Diabetes in Acute Pancreatitis Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.

“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told this news organization.

Dr. Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.

“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”

The study didn’t report funding support. Dr. Thiruvengadam and Dr. Forsmark report no relevant financial relationships.

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

Avocados are a rich source of fiber and healthy fat, but eating one a day for 6 months did not shrink waist size or belly fat, according to the findings of a new study.

But it did improve diet quality and led to modest lowering of total cholesterol.

More than 1,000 adults with overweight or obesity and a large waist – at least 35 inches in women and 40 inches in men – took part in this U.S. study, called the Habitual Diet and Avocado Trial (HAT).

tookapic/Pixabay

The people in the study were divided into two groups: usual diet plus one large avocado every day and usual diet with two avocados at most per month (control group).

Those in the avocado-a-day group were given a regular supply of fresh avocados along with written instructions for how to ripen and prepare them.

They had MRI scans to measure belly fat and fat around other organs at the beginning of the study and after 6 months.

After 6 months, the people who ate an avocado a day did not have less fat around their middles – the main trial outcome – compared with people in the control group.

But at 6 months, those in the avocado-a-day group had:

• No weight gain. People’s weight remained stable in both groups.
• Improved diet quality by 8 points on a 100-point scale
• A 2.9-mg/dL decrease in total cholesterol
• A 2.5-mg/dL decrease in LDL cholesterol

The study was done by researchers at Penn State University; Tufts University; Loma Linda University; and the University of California, Los Angeles, with coordinating support from Wake Forest University.

It was published in the Journal of the American Heart Association.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” Penny M. Kris-Etherton, PhD, one of the researchers and a professor of nutritional sciences at Penn State University, University Park, said in a news release.

“Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health,” she said.

Similarly, study researcher Joan Sabaté, MD, a professor at Loma Linda (Calif.) University, said: “While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain.”

“This is positive,” he said, “because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL cholesterol.”

Kristina S. Petersen, PhD, another of the researchers and an assistant professor of nutritional sciences at Texas Tech University, Lubbock, pointed out that people are generally poor at adhering to the Dietary Guidelines for Americans.

This study suggests that an avocado a day can improve diet quality, she noted, which “ is important because we know a higher diet quality is associated with lower risk of several diseases, including heart disease, type 2 diabetes, and some cancers.”

But the researchers also stressed that it is important to consider the diet as a whole.

“Consistent with prior observations, a change in dietary patterns rather than a single food or nutrient may be necessary to achieve clinically significant improvements” in belly fat and other risk factors for heart attack, stroke, and diabetes, they wrote. 

HAT was funded by the Hass Avocado Board, which also supplied the avocados.

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

Avocados are a rich source of fiber and healthy fat, but eating one a day for 6 months did not shrink waist size or belly fat, according to the findings of a new study.

But it did improve diet quality and led to modest lowering of total cholesterol.

More than 1,000 adults with overweight or obesity and a large waist – at least 35 inches in women and 40 inches in men – took part in this U.S. study, called the Habitual Diet and Avocado Trial (HAT).

tookapic/Pixabay

The people in the study were divided into two groups: usual diet plus one large avocado every day and usual diet with two avocados at most per month (control group).

Those in the avocado-a-day group were given a regular supply of fresh avocados along with written instructions for how to ripen and prepare them.

They had MRI scans to measure belly fat and fat around other organs at the beginning of the study and after 6 months.

After 6 months, the people who ate an avocado a day did not have less fat around their middles – the main trial outcome – compared with people in the control group.

But at 6 months, those in the avocado-a-day group had:

• No weight gain. People’s weight remained stable in both groups.
• Improved diet quality by 8 points on a 100-point scale
• A 2.9-mg/dL decrease in total cholesterol
• A 2.5-mg/dL decrease in LDL cholesterol

The study was done by researchers at Penn State University; Tufts University; Loma Linda University; and the University of California, Los Angeles, with coordinating support from Wake Forest University.

It was published in the Journal of the American Heart Association.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” Penny M. Kris-Etherton, PhD, one of the researchers and a professor of nutritional sciences at Penn State University, University Park, said in a news release.

“Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health,” she said.

Similarly, study researcher Joan Sabaté, MD, a professor at Loma Linda (Calif.) University, said: “While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain.”

“This is positive,” he said, “because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL cholesterol.”

Kristina S. Petersen, PhD, another of the researchers and an assistant professor of nutritional sciences at Texas Tech University, Lubbock, pointed out that people are generally poor at adhering to the Dietary Guidelines for Americans.

This study suggests that an avocado a day can improve diet quality, she noted, which “ is important because we know a higher diet quality is associated with lower risk of several diseases, including heart disease, type 2 diabetes, and some cancers.”

But the researchers also stressed that it is important to consider the diet as a whole.

“Consistent with prior observations, a change in dietary patterns rather than a single food or nutrient may be necessary to achieve clinically significant improvements” in belly fat and other risk factors for heart attack, stroke, and diabetes, they wrote. 

HAT was funded by the Hass Avocado Board, which also supplied the avocados.

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

Avocados are a rich source of fiber and healthy fat, but eating one a day for 6 months did not shrink waist size or belly fat, according to the findings of a new study.

But it did improve diet quality and led to modest lowering of total cholesterol.

More than 1,000 adults with overweight or obesity and a large waist – at least 35 inches in women and 40 inches in men – took part in this U.S. study, called the Habitual Diet and Avocado Trial (HAT).

tookapic/Pixabay

The people in the study were divided into two groups: usual diet plus one large avocado every day and usual diet with two avocados at most per month (control group).

Those in the avocado-a-day group were given a regular supply of fresh avocados along with written instructions for how to ripen and prepare them.

They had MRI scans to measure belly fat and fat around other organs at the beginning of the study and after 6 months.

After 6 months, the people who ate an avocado a day did not have less fat around their middles – the main trial outcome – compared with people in the control group.

But at 6 months, those in the avocado-a-day group had:

• No weight gain. People’s weight remained stable in both groups.
• Improved diet quality by 8 points on a 100-point scale
• A 2.9-mg/dL decrease in total cholesterol
• A 2.5-mg/dL decrease in LDL cholesterol

The study was done by researchers at Penn State University; Tufts University; Loma Linda University; and the University of California, Los Angeles, with coordinating support from Wake Forest University.

It was published in the Journal of the American Heart Association.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” Penny M. Kris-Etherton, PhD, one of the researchers and a professor of nutritional sciences at Penn State University, University Park, said in a news release.

“Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health,” she said.

Similarly, study researcher Joan Sabaté, MD, a professor at Loma Linda (Calif.) University, said: “While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain.”

“This is positive,” he said, “because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL cholesterol.”

Kristina S. Petersen, PhD, another of the researchers and an assistant professor of nutritional sciences at Texas Tech University, Lubbock, pointed out that people are generally poor at adhering to the Dietary Guidelines for Americans.

This study suggests that an avocado a day can improve diet quality, she noted, which “ is important because we know a higher diet quality is associated with lower risk of several diseases, including heart disease, type 2 diabetes, and some cancers.”

But the researchers also stressed that it is important to consider the diet as a whole.

“Consistent with prior observations, a change in dietary patterns rather than a single food or nutrient may be necessary to achieve clinically significant improvements” in belly fat and other risk factors for heart attack, stroke, and diabetes, they wrote. 

HAT was funded by the Hass Avocado Board, which also supplied the avocados.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

ILLUSTRATIVE CASE

A 62-year-old woman with a past medical history of type 2 diabetes, hyperlipidemia, hypertension, and remote myocardial infarction (MI) presents to her primary care office for a preventive visit. She is a nonsmoker and has been taking her daily medications as prescribed, including an angiotensin-converting enzyme inhibitor, high-intensity statin, and aspirin. Her diabetes is well controlled. What else would you consider recommending to decrease this patient’s risk for future CVEs?

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality, affecting more than 50% of patients older than 60.² Despite control of risk factors with standard treatment modalities, patients with established CVD remain at high risk for future events, which makes elucidating and targeting other causative pathways essential.³

Inflammation has been identified as a key player in the development and progression of atherosclerosis and its downstream effects, with increased inflammatory markers correlating with increased risk for CVEs.⁴ Due to these findings, anti-inflammatory treatments have been under investigation as agents to further reduce risk for CVEs. In 1 such trial, the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), patients with MI and elevated C-reactive protein levels treated with the interleukin-1 beta inhibitor canakinumab showed reduced risk for future CVEs compared to those receiving placebo.⁵ However, due to canakinumab’s high cost, inconvenient subcutaneous administration, and increased incidence of fatal infections, other agents are under investigation.

Colchicine is a potent anti-inflammatory agent, with approval in the United States for treatment of gout and familial Mediterranean fever. It works broadly to reduce inflammation by disrupting tubulin polymerization.^6,7 Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.^5,8 Colchicine’s oral administration, relative cost-effectiveness, and safety profile make it an attractive option for potential use in secondary prevention of CVEs.

The Low-Dose Colchicine (LoDoCo) trial, published in 2013, demonstrated a reduction in CVEs in those with CVD taking guideline-directed medical therapy (GDMT) plus colchicine 0.5 mg/d, compared with those taking GDMT alone.⁹ However, the LoDoCo study enrolled only 532 patients and was not placebo controlled. The Colchicine Cardiovascular Outcomes Trial (COLCOT), published in 2019, was a randomized, ­double-blind, placebo-controlled trial that aimed to further evaluate the effects of colchicine on CVEs on a larger scale and to assess its longer-term safety.¹⁰ In this study, the colchicine group had a significantly lower risk of CVEs vs placebo, with a comparable safety profile.¹⁰

STUDY SUMMARY

Fewer CVEs occurred when colchicine was added to the regimen

The randomized, multicenter, double-blind Low Dose Colchicine 2 (LoDoCo2) trial evaluated whether colchicine 0.5 mg daily reduces CV death, spontaneous (nonprocedural) MI, ischemic stroke, or ischemia-driven coronary revascularization in patients with chronic CAD (composite primary endpoint). This trial included 5522 patients, ages 35 to 82, in Australia and the Netherlands. Patients were eligible to participate if they had evidence of CAD by invasive coronary angiography, coronary calcium score, or computed tomography angiography, as well as evidence of clinical stability for 6 months. Exclusion criteria included moderate-to-severe renal impairment, severe heart failure, severe valvular disease, or intolerance to colchicine.

Patients (N = 6528) took colchicine 0.5 mg daily as part of a 1-month, open-label run-in phase; 1006 patients stopped taking colchicine during this time. Perceived adverse effects were observed in 611 of these patients, the most common being gastrointestinal (GI) upset (437 patients). After the run-in phase, the remaining 5522 patients were randomized to either the colchicine or placebo group. Both groups continued to receive GDMT for CVD, including antiplatelet therapy, anticoagulants, and hypertensive therapy as indicated. Lipid-lowering therapies were continued in 96.7% of the colchicine group and 96.6% of the placebo group. These patients were then followed for a minimum of 1 year (median duration, 28.6 months).

Continue to: The primary endpoint...

The primary endpoint occurred less frequently in the colchicine group than in the placebo group (6.8% vs 9.6%; P < .001; number needed to treat = 36). The incidence rates for 2 of the individual outcomes in the composite, MI (hazard ratio [HR] = 0.7; 95% CI, 0.53-0.93) and ischemia-driven coronary revascularization (HR = 0.75; 95% CI, 0.60-0.94), were significantly lower in the colchicine group. The other outcomes were no different from placebo.¹

There was a similar incidence of serious adverse events, such as noncardiovascular death, cancer diagnosis, and hospitalization for infection, pneumonia, or GI issues. High-dose statins were used by 3413 patients (61.8%). Myalgia (data collected only from the Netherlands cohort) was reported more commonly in the colchicine group than the placebo group (21.2% vs 18.5%; cumulative incidence ratio = 1.15; 95% CI, 1.01-1.31). Myotoxic effects were rare in both groups.¹

WHAT’S NEW

RCT supports potential for anti-inflammatory therapy in CAD

This large RCT demonstrated that the addition of daily colchicine reduces CVE risk in patients with known CAD while maintaining a good safety profile.¹

CAVEATS

Watch for potential drug interactions in patients with renal dysfunction

Prescribers should be aware of potential drug interactions, especially in those with renal or hepatic dysfunction, when prescribing colchicine, as it is metabolized through cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein transport system, by which many statins are also metabolized and act as a competitive substrate.⁷ In addition, simvastatin, and to a lesser degree atorvastatin, are CYP3A4 inhibitors.

Also of note, the 0.5-mg colchicine tablet is not available in some countries—including the United States, where only 0.6-mg tablets are available. The 0.6-mg dose would likely have the same benefit and similar adverse effect profile but was not included in the study.

CHALLENGES TO IMPLEMENTATION

GI tolerability may be an issue

Colchicine is widely available and relatively low in cost, at approximately $32 per month for the 0.6-mg daily tablets. A major limitation is lack of tolerability, as adverse effects such as nausea, vomiting, diarrhea, and abdominal pain are frequently reported.

ILLUSTRATIVE CASE

A 62-year-old woman with a past medical history of type 2 diabetes, hyperlipidemia, hypertension, and remote myocardial infarction (MI) presents to her primary care office for a preventive visit. She is a nonsmoker and has been taking her daily medications as prescribed, including an angiotensin-converting enzyme inhibitor, high-intensity statin, and aspirin. Her diabetes is well controlled. What else would you consider recommending to decrease this patient’s risk for future CVEs?

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality, affecting more than 50% of patients older than 60.² Despite control of risk factors with standard treatment modalities, patients with established CVD remain at high risk for future events, which makes elucidating and targeting other causative pathways essential.³

Inflammation has been identified as a key player in the development and progression of atherosclerosis and its downstream effects, with increased inflammatory markers correlating with increased risk for CVEs.⁴ Due to these findings, anti-inflammatory treatments have been under investigation as agents to further reduce risk for CVEs. In 1 such trial, the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), patients with MI and elevated C-reactive protein levels treated with the interleukin-1 beta inhibitor canakinumab showed reduced risk for future CVEs compared to those receiving placebo.⁵ However, due to canakinumab’s high cost, inconvenient subcutaneous administration, and increased incidence of fatal infections, other agents are under investigation.

Colchicine is a potent anti-inflammatory agent, with approval in the United States for treatment of gout and familial Mediterranean fever. It works broadly to reduce inflammation by disrupting tubulin polymerization.^6,7 Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.^5,8 Colchicine’s oral administration, relative cost-effectiveness, and safety profile make it an attractive option for potential use in secondary prevention of CVEs.

The Low-Dose Colchicine (LoDoCo) trial, published in 2013, demonstrated a reduction in CVEs in those with CVD taking guideline-directed medical therapy (GDMT) plus colchicine 0.5 mg/d, compared with those taking GDMT alone.⁹ However, the LoDoCo study enrolled only 532 patients and was not placebo controlled. The Colchicine Cardiovascular Outcomes Trial (COLCOT), published in 2019, was a randomized, ­double-blind, placebo-controlled trial that aimed to further evaluate the effects of colchicine on CVEs on a larger scale and to assess its longer-term safety.¹⁰ In this study, the colchicine group had a significantly lower risk of CVEs vs placebo, with a comparable safety profile.¹⁰

STUDY SUMMARY

Fewer CVEs occurred when colchicine was added to the regimen

The randomized, multicenter, double-blind Low Dose Colchicine 2 (LoDoCo2) trial evaluated whether colchicine 0.5 mg daily reduces CV death, spontaneous (nonprocedural) MI, ischemic stroke, or ischemia-driven coronary revascularization in patients with chronic CAD (composite primary endpoint). This trial included 5522 patients, ages 35 to 82, in Australia and the Netherlands. Patients were eligible to participate if they had evidence of CAD by invasive coronary angiography, coronary calcium score, or computed tomography angiography, as well as evidence of clinical stability for 6 months. Exclusion criteria included moderate-to-severe renal impairment, severe heart failure, severe valvular disease, or intolerance to colchicine.

Patients (N = 6528) took colchicine 0.5 mg daily as part of a 1-month, open-label run-in phase; 1006 patients stopped taking colchicine during this time. Perceived adverse effects were observed in 611 of these patients, the most common being gastrointestinal (GI) upset (437 patients). After the run-in phase, the remaining 5522 patients were randomized to either the colchicine or placebo group. Both groups continued to receive GDMT for CVD, including antiplatelet therapy, anticoagulants, and hypertensive therapy as indicated. Lipid-lowering therapies were continued in 96.7% of the colchicine group and 96.6% of the placebo group. These patients were then followed for a minimum of 1 year (median duration, 28.6 months).

Continue to: The primary endpoint...

The primary endpoint occurred less frequently in the colchicine group than in the placebo group (6.8% vs 9.6%; P < .001; number needed to treat = 36). The incidence rates for 2 of the individual outcomes in the composite, MI (hazard ratio [HR] = 0.7; 95% CI, 0.53-0.93) and ischemia-driven coronary revascularization (HR = 0.75; 95% CI, 0.60-0.94), were significantly lower in the colchicine group. The other outcomes were no different from placebo.¹

There was a similar incidence of serious adverse events, such as noncardiovascular death, cancer diagnosis, and hospitalization for infection, pneumonia, or GI issues. High-dose statins were used by 3413 patients (61.8%). Myalgia (data collected only from the Netherlands cohort) was reported more commonly in the colchicine group than the placebo group (21.2% vs 18.5%; cumulative incidence ratio = 1.15; 95% CI, 1.01-1.31). Myotoxic effects were rare in both groups.¹

WHAT’S NEW

RCT supports potential for anti-inflammatory therapy in CAD

This large RCT demonstrated that the addition of daily colchicine reduces CVE risk in patients with known CAD while maintaining a good safety profile.¹

CAVEATS

Watch for potential drug interactions in patients with renal dysfunction

Prescribers should be aware of potential drug interactions, especially in those with renal or hepatic dysfunction, when prescribing colchicine, as it is metabolized through cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein transport system, by which many statins are also metabolized and act as a competitive substrate.⁷ In addition, simvastatin, and to a lesser degree atorvastatin, are CYP3A4 inhibitors.

Also of note, the 0.5-mg colchicine tablet is not available in some countries—including the United States, where only 0.6-mg tablets are available. The 0.6-mg dose would likely have the same benefit and similar adverse effect profile but was not included in the study.

CHALLENGES TO IMPLEMENTATION

GI tolerability may be an issue

Colchicine is widely available and relatively low in cost, at approximately $32 per month for the 0.6-mg daily tablets. A major limitation is lack of tolerability, as adverse effects such as nausea, vomiting, diarrhea, and abdominal pain are frequently reported.

ILLUSTRATIVE CASE

A 62-year-old woman with a past medical history of type 2 diabetes, hyperlipidemia, hypertension, and remote myocardial infarction (MI) presents to her primary care office for a preventive visit. She is a nonsmoker and has been taking her daily medications as prescribed, including an angiotensin-converting enzyme inhibitor, high-intensity statin, and aspirin. Her diabetes is well controlled. What else would you consider recommending to decrease this patient’s risk for future CVEs?

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality, affecting more than 50% of patients older than 60.² Despite control of risk factors with standard treatment modalities, patients with established CVD remain at high risk for future events, which makes elucidating and targeting other causative pathways essential.³

Inflammation has been identified as a key player in the development and progression of atherosclerosis and its downstream effects, with increased inflammatory markers correlating with increased risk for CVEs.⁴ Due to these findings, anti-inflammatory treatments have been under investigation as agents to further reduce risk for CVEs. In 1 such trial, the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), patients with MI and elevated C-reactive protein levels treated with the interleukin-1 beta inhibitor canakinumab showed reduced risk for future CVEs compared to those receiving placebo.⁵ However, due to canakinumab’s high cost, inconvenient subcutaneous administration, and increased incidence of fatal infections, other agents are under investigation.

Colchicine is a potent anti-inflammatory agent, with approval in the United States for treatment of gout and familial Mediterranean fever. It works broadly to reduce inflammation by disrupting tubulin polymerization.^6,7 Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.^5,8 Colchicine’s oral administration, relative cost-effectiveness, and safety profile make it an attractive option for potential use in secondary prevention of CVEs.

The Low-Dose Colchicine (LoDoCo) trial, published in 2013, demonstrated a reduction in CVEs in those with CVD taking guideline-directed medical therapy (GDMT) plus colchicine 0.5 mg/d, compared with those taking GDMT alone.⁹ However, the LoDoCo study enrolled only 532 patients and was not placebo controlled. The Colchicine Cardiovascular Outcomes Trial (COLCOT), published in 2019, was a randomized, ­double-blind, placebo-controlled trial that aimed to further evaluate the effects of colchicine on CVEs on a larger scale and to assess its longer-term safety.¹⁰ In this study, the colchicine group had a significantly lower risk of CVEs vs placebo, with a comparable safety profile.¹⁰

STUDY SUMMARY

Fewer CVEs occurred when colchicine was added to the regimen

The randomized, multicenter, double-blind Low Dose Colchicine 2 (LoDoCo2) trial evaluated whether colchicine 0.5 mg daily reduces CV death, spontaneous (nonprocedural) MI, ischemic stroke, or ischemia-driven coronary revascularization in patients with chronic CAD (composite primary endpoint). This trial included 5522 patients, ages 35 to 82, in Australia and the Netherlands. Patients were eligible to participate if they had evidence of CAD by invasive coronary angiography, coronary calcium score, or computed tomography angiography, as well as evidence of clinical stability for 6 months. Exclusion criteria included moderate-to-severe renal impairment, severe heart failure, severe valvular disease, or intolerance to colchicine.

Patients (N = 6528) took colchicine 0.5 mg daily as part of a 1-month, open-label run-in phase; 1006 patients stopped taking colchicine during this time. Perceived adverse effects were observed in 611 of these patients, the most common being gastrointestinal (GI) upset (437 patients). After the run-in phase, the remaining 5522 patients were randomized to either the colchicine or placebo group. Both groups continued to receive GDMT for CVD, including antiplatelet therapy, anticoagulants, and hypertensive therapy as indicated. Lipid-lowering therapies were continued in 96.7% of the colchicine group and 96.6% of the placebo group. These patients were then followed for a minimum of 1 year (median duration, 28.6 months).

Continue to: The primary endpoint...

The primary endpoint occurred less frequently in the colchicine group than in the placebo group (6.8% vs 9.6%; P < .001; number needed to treat = 36). The incidence rates for 2 of the individual outcomes in the composite, MI (hazard ratio [HR] = 0.7; 95% CI, 0.53-0.93) and ischemia-driven coronary revascularization (HR = 0.75; 95% CI, 0.60-0.94), were significantly lower in the colchicine group. The other outcomes were no different from placebo.¹

There was a similar incidence of serious adverse events, such as noncardiovascular death, cancer diagnosis, and hospitalization for infection, pneumonia, or GI issues. High-dose statins were used by 3413 patients (61.8%). Myalgia (data collected only from the Netherlands cohort) was reported more commonly in the colchicine group than the placebo group (21.2% vs 18.5%; cumulative incidence ratio = 1.15; 95% CI, 1.01-1.31). Myotoxic effects were rare in both groups.¹

WHAT’S NEW

RCT supports potential for anti-inflammatory therapy in CAD

This large RCT demonstrated that the addition of daily colchicine reduces CVE risk in patients with known CAD while maintaining a good safety profile.¹

CAVEATS

Watch for potential drug interactions in patients with renal dysfunction

Prescribers should be aware of potential drug interactions, especially in those with renal or hepatic dysfunction, when prescribing colchicine, as it is metabolized through cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein transport system, by which many statins are also metabolized and act as a competitive substrate.⁷ In addition, simvastatin, and to a lesser degree atorvastatin, are CYP3A4 inhibitors.

Also of note, the 0.5-mg colchicine tablet is not available in some countries—including the United States, where only 0.6-mg tablets are available. The 0.6-mg dose would likely have the same benefit and similar adverse effect profile but was not included in the study.

CHALLENGES TO IMPLEMENTATION

GI tolerability may be an issue

Colchicine is widely available and relatively low in cost, at approximately $32 per month for the 0.6-mg daily tablets. A major limitation is lack of tolerability, as adverse effects such as nausea, vomiting, diarrhea, and abdominal pain are frequently reported.

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

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

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

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

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

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

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

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

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

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

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

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

In April 2022, the US Preventive Services Task Force (USPSTF) issued new recommendations for the use of aspirin to prevent cardiovascular disease (CVD).¹ These recommendations differ markedly from those issued in 2016.

First, for individuals ages 40 through 59 years who have a ≥ 10% 10-year risk of CVD, the decision to initiate low-dose aspirin to prevent CVD is selective. This is in contrast to the 2016 recommendation that advised offering aspirin to any individual ages 50 to 59 whose 10-year risk of CVD was ≥ 10% and whose life expectancy was at least 10 years (TABLE).

Second, according to the new recommendations, individuals who are ages 60 years and older should not initiate low-dose aspirin for the primary prevention of CVD. Previously, selected individuals ages 60 to 69 could be advised to take low-dose aspirin.

The 2016 recommendations also considered the potential benefit of aspirin for preventing colorectal cancer. The 2022 recommendations are silent on this topic, because the USPSTF now concludes that the evidence is insufficient to form an opinion about it.

Important details to keep in mind

These new recommendations pertain to those without signs or symptoms of CVD or known CVD. They do not apply to the use of aspirin for harm reduction or tertiary prevention in those with known CVD. Moreover, the recommendations address the initiation of aspirin at the suggested dose of 81 mg/d, not the continuation of it by those already using it (more on this later). The tool recommended for calculating 10-year CVD risk is the one developed by the American College of Cardiology (ACC) and the American Heart Association (AHA) (www.cvriskcalculator.com).

An ongoing controversy. Daily low-dose aspirin for the prevention of CVD has been controversial for decades. The TABLE shows how USPSTF recommendations on this topic have changed from 2009 to the present. In 2009, the recommendations were primarily based on 2 studies; today, they are based on 13 studies and a microsimulation to estimate the benefits and harms of aspirin prophylaxis at different patient ages.² This increase in the quantity of the evidence, as well as the elevation in quality, has led to much more nuanced and conservative recommendations. These new recommendations from the USPSTF align much more closely with those of the ACC and the AHA, differing only on the upper age limit at which aspirin initiation should be discouraged (60 years for the USPSTF, 70 for ACC/AHA).

Advise aspirin use selectively per the USPSTF recommendations

Several issues must be addressed when considering daily aspirin use for those ages 40 through 59 years (C recommendation; see TABLE for grade definitions):

• Risk of bleeding is elevated with past or current peptic ulcer disease, diabetes, smoking, high blood pressure, and the use of anti-inflammatory medications, steroids, and anticoagulants.
• The harms from bleeding complications tend to occur early in the use of aspirin and can include gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke.
• The higher the 10-year CVD risk, the greater the benefit from low-dose aspirin.
• Benefits of aspirin for the prevention of CVD increase with the number of years of use.
• If an individual has been taking low-dose aspirin without complications, a reasonable age to discontinue its use is 75 years because little incremental benefit occurs with use after that age.

Continue to: More on low-dose aspirin benefits and harms

More on low-dose aspirin benefits and harms. What exactly is the absolute benefit and harm from daily low-dose aspirin use for primary prevention of CVD? As one might expect, it varies by age. Researchers used a microsimulation model to examine updated clinical data from systematic reviews. Looking at life years gained, the largest benefit was in men with a 10-year CVD risk of 20% and aspirin initiated between the ages of 40 and 49.³ This resulted in 52.4 lifetime years gained per 1000 people.³ The results from a meta-analysis of 11 studies, published in the evidence report, found an absolute reduction in major CVD events of 0.4% (number needed to treat = 250) and an absolute increase in major bleeds of 0.5% (number needed to harm = 200).² There was no reduction found for CVD-related or all-cause deaths.

One reason for the increased caution on using aspirin as primary prevention for CVD is the role that statins now play in reducing CVD risk, a factor not accounted for in the studies assessed. It is unknown if the addition of aspirin to statins is beneficial. Remember that the USPSTF recommends the use of a low- to moderate-dose statin in those ages 40 to 75 years if they have one or more CVD risk factors and a 10-year CVD risk ≥ 10%.⁴

How aspirin use might change. The use of aspirin for CVD prevention is widespread. One analysis estimates that one-third of those ages 50 years and older are using aspirin for CVD prevention, including 45% of those older than 75.⁵ If the recommendations from the USPSTF are widely adopted, there could be a gradual decrease in aspirin use for primary prevention with little or no effect on overall population health. Other interventions such as smoking prevention, weight reduction, high blood pressure control, and targeted use of statins—if more widely used—would contribute to the downward trend in CVD deaths that has occurred over the past several decades, with fewer complications caused by regular aspirin use.

Take-home message

Follow these steps when caring for adults ages 40 years and older who do not have known CVD:

1. Assess their 10-year CVD risk using the ACC/AHA tool. If the risk is ≥ 10%:

• Discuss the use of a low- or ­moderate-dose statin if they are age 75 years or younger.
• Discuss the potential for benefit and harm of low-dose aspirin if they are between the ages of 40 and 59 years.
• Mention to those taking daily low-dose aspirin that it has low benefit if continued after age 75.

2. Perform these interventions:

• Screen for hypertension and high cholesterol.
• Screen for type 2 diabetes and pre-diabetes in patients up to age 70 years who are overweight or obese.
• Ask about smoking.
• Measure body mass index.
• Offer preventive interventions when any of these CVD risks are found.

In April 2022, the US Preventive Services Task Force (USPSTF) issued new recommendations for the use of aspirin to prevent cardiovascular disease (CVD).¹ These recommendations differ markedly from those issued in 2016.

First, for individuals ages 40 through 59 years who have a ≥ 10% 10-year risk of CVD, the decision to initiate low-dose aspirin to prevent CVD is selective. This is in contrast to the 2016 recommendation that advised offering aspirin to any individual ages 50 to 59 whose 10-year risk of CVD was ≥ 10% and whose life expectancy was at least 10 years (TABLE).

Second, according to the new recommendations, individuals who are ages 60 years and older should not initiate low-dose aspirin for the primary prevention of CVD. Previously, selected individuals ages 60 to 69 could be advised to take low-dose aspirin.

The 2016 recommendations also considered the potential benefit of aspirin for preventing colorectal cancer. The 2022 recommendations are silent on this topic, because the USPSTF now concludes that the evidence is insufficient to form an opinion about it.

Important details to keep in mind

These new recommendations pertain to those without signs or symptoms of CVD or known CVD. They do not apply to the use of aspirin for harm reduction or tertiary prevention in those with known CVD. Moreover, the recommendations address the initiation of aspirin at the suggested dose of 81 mg/d, not the continuation of it by those already using it (more on this later). The tool recommended for calculating 10-year CVD risk is the one developed by the American College of Cardiology (ACC) and the American Heart Association (AHA) (www.cvriskcalculator.com).

An ongoing controversy. Daily low-dose aspirin for the prevention of CVD has been controversial for decades. The TABLE shows how USPSTF recommendations on this topic have changed from 2009 to the present. In 2009, the recommendations were primarily based on 2 studies; today, they are based on 13 studies and a microsimulation to estimate the benefits and harms of aspirin prophylaxis at different patient ages.² This increase in the quantity of the evidence, as well as the elevation in quality, has led to much more nuanced and conservative recommendations. These new recommendations from the USPSTF align much more closely with those of the ACC and the AHA, differing only on the upper age limit at which aspirin initiation should be discouraged (60 years for the USPSTF, 70 for ACC/AHA).

Advise aspirin use selectively per the USPSTF recommendations

Several issues must be addressed when considering daily aspirin use for those ages 40 through 59 years (C recommendation; see TABLE for grade definitions):

• Risk of bleeding is elevated with past or current peptic ulcer disease, diabetes, smoking, high blood pressure, and the use of anti-inflammatory medications, steroids, and anticoagulants.
• The harms from bleeding complications tend to occur early in the use of aspirin and can include gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke.
• The higher the 10-year CVD risk, the greater the benefit from low-dose aspirin.
• Benefits of aspirin for the prevention of CVD increase with the number of years of use.
• If an individual has been taking low-dose aspirin without complications, a reasonable age to discontinue its use is 75 years because little incremental benefit occurs with use after that age.

Continue to: More on low-dose aspirin benefits and harms

More on low-dose aspirin benefits and harms. What exactly is the absolute benefit and harm from daily low-dose aspirin use for primary prevention of CVD? As one might expect, it varies by age. Researchers used a microsimulation model to examine updated clinical data from systematic reviews. Looking at life years gained, the largest benefit was in men with a 10-year CVD risk of 20% and aspirin initiated between the ages of 40 and 49.³ This resulted in 52.4 lifetime years gained per 1000 people.³ The results from a meta-analysis of 11 studies, published in the evidence report, found an absolute reduction in major CVD events of 0.4% (number needed to treat = 250) and an absolute increase in major bleeds of 0.5% (number needed to harm = 200).² There was no reduction found for CVD-related or all-cause deaths.

One reason for the increased caution on using aspirin as primary prevention for CVD is the role that statins now play in reducing CVD risk, a factor not accounted for in the studies assessed. It is unknown if the addition of aspirin to statins is beneficial. Remember that the USPSTF recommends the use of a low- to moderate-dose statin in those ages 40 to 75 years if they have one or more CVD risk factors and a 10-year CVD risk ≥ 10%.⁴

How aspirin use might change. The use of aspirin for CVD prevention is widespread. One analysis estimates that one-third of those ages 50 years and older are using aspirin for CVD prevention, including 45% of those older than 75.⁵ If the recommendations from the USPSTF are widely adopted, there could be a gradual decrease in aspirin use for primary prevention with little or no effect on overall population health. Other interventions such as smoking prevention, weight reduction, high blood pressure control, and targeted use of statins—if more widely used—would contribute to the downward trend in CVD deaths that has occurred over the past several decades, with fewer complications caused by regular aspirin use.

Take-home message

Follow these steps when caring for adults ages 40 years and older who do not have known CVD:

1. Assess their 10-year CVD risk using the ACC/AHA tool. If the risk is ≥ 10%:

• Discuss the use of a low- or ­moderate-dose statin if they are age 75 years or younger.
• Discuss the potential for benefit and harm of low-dose aspirin if they are between the ages of 40 and 59 years.
• Mention to those taking daily low-dose aspirin that it has low benefit if continued after age 75.

2. Perform these interventions:

• Screen for hypertension and high cholesterol.
• Screen for type 2 diabetes and pre-diabetes in patients up to age 70 years who are overweight or obese.
• Ask about smoking.
• Measure body mass index.
• Offer preventive interventions when any of these CVD risks are found.

In April 2022, the US Preventive Services Task Force (USPSTF) issued new recommendations for the use of aspirin to prevent cardiovascular disease (CVD).¹ These recommendations differ markedly from those issued in 2016.

First, for individuals ages 40 through 59 years who have a ≥ 10% 10-year risk of CVD, the decision to initiate low-dose aspirin to prevent CVD is selective. This is in contrast to the 2016 recommendation that advised offering aspirin to any individual ages 50 to 59 whose 10-year risk of CVD was ≥ 10% and whose life expectancy was at least 10 years (TABLE).

Second, according to the new recommendations, individuals who are ages 60 years and older should not initiate low-dose aspirin for the primary prevention of CVD. Previously, selected individuals ages 60 to 69 could be advised to take low-dose aspirin.

The 2016 recommendations also considered the potential benefit of aspirin for preventing colorectal cancer. The 2022 recommendations are silent on this topic, because the USPSTF now concludes that the evidence is insufficient to form an opinion about it.

Important details to keep in mind

These new recommendations pertain to those without signs or symptoms of CVD or known CVD. They do not apply to the use of aspirin for harm reduction or tertiary prevention in those with known CVD. Moreover, the recommendations address the initiation of aspirin at the suggested dose of 81 mg/d, not the continuation of it by those already using it (more on this later). The tool recommended for calculating 10-year CVD risk is the one developed by the American College of Cardiology (ACC) and the American Heart Association (AHA) (www.cvriskcalculator.com).

An ongoing controversy. Daily low-dose aspirin for the prevention of CVD has been controversial for decades. The TABLE shows how USPSTF recommendations on this topic have changed from 2009 to the present. In 2009, the recommendations were primarily based on 2 studies; today, they are based on 13 studies and a microsimulation to estimate the benefits and harms of aspirin prophylaxis at different patient ages.² This increase in the quantity of the evidence, as well as the elevation in quality, has led to much more nuanced and conservative recommendations. These new recommendations from the USPSTF align much more closely with those of the ACC and the AHA, differing only on the upper age limit at which aspirin initiation should be discouraged (60 years for the USPSTF, 70 for ACC/AHA).

Advise aspirin use selectively per the USPSTF recommendations

Several issues must be addressed when considering daily aspirin use for those ages 40 through 59 years (C recommendation; see TABLE for grade definitions):

• Risk of bleeding is elevated with past or current peptic ulcer disease, diabetes, smoking, high blood pressure, and the use of anti-inflammatory medications, steroids, and anticoagulants.
• The harms from bleeding complications tend to occur early in the use of aspirin and can include gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke.
• The higher the 10-year CVD risk, the greater the benefit from low-dose aspirin.
• Benefits of aspirin for the prevention of CVD increase with the number of years of use.
• If an individual has been taking low-dose aspirin without complications, a reasonable age to discontinue its use is 75 years because little incremental benefit occurs with use after that age.

Continue to: More on low-dose aspirin benefits and harms

More on low-dose aspirin benefits and harms. What exactly is the absolute benefit and harm from daily low-dose aspirin use for primary prevention of CVD? As one might expect, it varies by age. Researchers used a microsimulation model to examine updated clinical data from systematic reviews. Looking at life years gained, the largest benefit was in men with a 10-year CVD risk of 20% and aspirin initiated between the ages of 40 and 49.³ This resulted in 52.4 lifetime years gained per 1000 people.³ The results from a meta-analysis of 11 studies, published in the evidence report, found an absolute reduction in major CVD events of 0.4% (number needed to treat = 250) and an absolute increase in major bleeds of 0.5% (number needed to harm = 200).² There was no reduction found for CVD-related or all-cause deaths.

One reason for the increased caution on using aspirin as primary prevention for CVD is the role that statins now play in reducing CVD risk, a factor not accounted for in the studies assessed. It is unknown if the addition of aspirin to statins is beneficial. Remember that the USPSTF recommends the use of a low- to moderate-dose statin in those ages 40 to 75 years if they have one or more CVD risk factors and a 10-year CVD risk ≥ 10%.⁴

How aspirin use might change. The use of aspirin for CVD prevention is widespread. One analysis estimates that one-third of those ages 50 years and older are using aspirin for CVD prevention, including 45% of those older than 75.⁵ If the recommendations from the USPSTF are widely adopted, there could be a gradual decrease in aspirin use for primary prevention with little or no effect on overall population health. Other interventions such as smoking prevention, weight reduction, high blood pressure control, and targeted use of statins—if more widely used—would contribute to the downward trend in CVD deaths that has occurred over the past several decades, with fewer complications caused by regular aspirin use.

Take-home message

Follow these steps when caring for adults ages 40 years and older who do not have known CVD:

1. Assess their 10-year CVD risk using the ACC/AHA tool. If the risk is ≥ 10%:

• Discuss the use of a low- or ­moderate-dose statin if they are age 75 years or younger.
• Discuss the potential for benefit and harm of low-dose aspirin if they are between the ages of 40 and 59 years.
• Mention to those taking daily low-dose aspirin that it has low benefit if continued after age 75.

2. Perform these interventions:

• Screen for hypertension and high cholesterol.
• Screen for type 2 diabetes and pre-diabetes in patients up to age 70 years who are overweight or obese.
• Ask about smoking.
• Measure body mass index.
• Offer preventive interventions when any of these CVD risks are found.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

The stress of losing a family member can hasten the death of patients with heart failure, suggests a large Swedish study that points to the need for greater integration of psychosocial risk factors in the treatment of HF.

The adjusted relative risk of dying was nearly 30% higher among bereaved patients with HF (1.29; 95% confidence interval, 1.27-1.30) and slightly higher for those grieving the loss of more than one family member (RR, 1.35).

The highest risk was in the first week after the loss (RR, 1.78) but persisted after 5 years of follow-up (RR, 1.30).

“Heart failure is a very difficult condition and has a very poor prognosis comparable to many, many cancers,” senior author Krisztina László, PhD, Karolinska Institutet, Stockholm, said in an interview. “So it’s important for us to be aware of these increased risks and to understand them better.”

The early risk for death could be related to stress-induced cardiomyopathy, or Takotsubo syndrome, as well as activation of the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system, and sympathetic nervous system, she explained. Higher long-term risks may reflect chronic stress, leading to poorly managed disease and an unhealthy lifestyle.

“If we understand better the underlying mechanisms maybe we can give more specific advice,” Dr. László said. “At this stage, I think having an awareness of the risk and trying to follow patients or at least not let them fall out of usual care, asking questions, trying to understand what their needs are, maybe that is what we can do well.”

A recent position paper by the European Association of Preventive Cardiology pointed out that psychosocial risk factors, like depression and social isolation, can exacerbate heart failure and calls for better integration of psychosocial factors in the treatment of patients with chronic HF.

“We don’t do a very good job of it, but I think they are very important,” observed Stuart D. Russell, MD, a professor of medicine who specializes in advanced HF at Duke University, Durham, N.C., and was not involved in the study.

“When we hear about a spouse dying, we might call and give condolences, but it’s probably a group of patients that for the next 6 months or so we need to watch more closely and see if there are things we can impact both medically as well as socially to perhaps prevent some of this increase in mortality,” he told this news organization.

Although several studies have linked bereavement with adverse health outcomes, this is just one of two studies to look specifically at its role in HF prognosis, Dr. László noted. A 2013 study of 66,000 male veterans reported that widowers had nearly a 38% higher all-cause mortality risk than did married veterans.

The present study extends those findings to 490,527 patients in the Swedish Heart Failure Registry between 2000 and 2018 and/or in the Swedish Patient Register with a primary diagnosis of HF between 1987 and 2018. During a mean follow-up of 3.7 years, 12% of participants had a family member die, and 383,674 participants died.

Results showed the HF mortality risk increased 10% after the death of a child, 20% with the death of a spouse/partner, 13% with a sibling’s death, and 5% with the death of a grandchild.

No increased risk was seen after the death of a parent, which is likely owed to a median patient age of about 75 years and “is in line with our expectations of the life cycle,” Dr. László said.

An association between bereavement and mortality risk was observed in cases of loss caused by cardiovascular disease (RR, 1.34) and other natural causes (RR, 1.27) but also in cases of unnatural deaths, such as suicide (RR, 1.13).

The overall findings were similar regardless of left ventricular ejection fraction and New York Heart Association functional class and were not affected by sex or country of birth.

Dr. Russell agreed that the death of a parent would be expected among these older patients with HF but said that “if the mechanism of this truly is kind of this increased stress hormones and Takotsubo-type mechanism, you’d think it would be worse if it was your kid that died. That shocked me a bit.”

The strong association between mortality and the loss of a spouse or partner was not surprising, given that they’re an important source of mutual social support, he added.

“If it’s a 75-year-old whose spouse dies, we need to make sure that we have the children’s phone number or other people that we can reach out to and say: ‘Can you check on them?’ ” he said. “And we need to make sure that somebody else is coming in with them because I would guess that probably at least half of what patients hear in a clinic visit goes in one ear and out the other and it’s going to make that much better. So we need to find who that new support person is for the patient.”

Asked whether there are efforts underway to incorporate psychosocial factors into current U.S. guidelines, Dr. Russell replied, “certainly within heart failure, I don’t think we’re really discussing it and, that may be the best part of this paper. It really makes us think about a different way of approaching these older patients.”

Dr. László said that future studies are needed to investigate whether less severe sources of stress may also contribute to poor HF prognosis.

“In our population, 12% of patients were affected, which is quite high, but there are patients with heart failure who experience on a daily basis other sources of stress, which are less severe but chronic and affect large numbers,” she said. “This may also have important public health implications and will be an important next step.”

The authors noted that they were unable to eliminate residual confounding by genetic factors or unmeasured socioeconomic-, lifestyle-, or health-related factors shared by family members. Other limitations are limited power to detect a modest effect in some of the subanalyses and that the findings may be generalizable only to countries with social and cultural contexts and health-related factors similar to those of Sweden.

The study was supported by grants from the Swedish Council for Working Life and Social Research, the Karolinska Institutet’s Research Foundation, and the China Scholarship Council. Dr. László is also supported by a grant from the Heart and Lung Foundation. All other authors and Dr. Russell reported no relevant financial relationships.

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

The stress of losing a family member can hasten the death of patients with heart failure, suggests a large Swedish study that points to the need for greater integration of psychosocial risk factors in the treatment of HF.

The adjusted relative risk of dying was nearly 30% higher among bereaved patients with HF (1.29; 95% confidence interval, 1.27-1.30) and slightly higher for those grieving the loss of more than one family member (RR, 1.35).

The highest risk was in the first week after the loss (RR, 1.78) but persisted after 5 years of follow-up (RR, 1.30).

“Heart failure is a very difficult condition and has a very poor prognosis comparable to many, many cancers,” senior author Krisztina László, PhD, Karolinska Institutet, Stockholm, said in an interview. “So it’s important for us to be aware of these increased risks and to understand them better.”

The early risk for death could be related to stress-induced cardiomyopathy, or Takotsubo syndrome, as well as activation of the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system, and sympathetic nervous system, she explained. Higher long-term risks may reflect chronic stress, leading to poorly managed disease and an unhealthy lifestyle.

“If we understand better the underlying mechanisms maybe we can give more specific advice,” Dr. László said. “At this stage, I think having an awareness of the risk and trying to follow patients or at least not let them fall out of usual care, asking questions, trying to understand what their needs are, maybe that is what we can do well.”

A recent position paper by the European Association of Preventive Cardiology pointed out that psychosocial risk factors, like depression and social isolation, can exacerbate heart failure and calls for better integration of psychosocial factors in the treatment of patients with chronic HF.

“We don’t do a very good job of it, but I think they are very important,” observed Stuart D. Russell, MD, a professor of medicine who specializes in advanced HF at Duke University, Durham, N.C., and was not involved in the study.

“When we hear about a spouse dying, we might call and give condolences, but it’s probably a group of patients that for the next 6 months or so we need to watch more closely and see if there are things we can impact both medically as well as socially to perhaps prevent some of this increase in mortality,” he told this news organization.

Although several studies have linked bereavement with adverse health outcomes, this is just one of two studies to look specifically at its role in HF prognosis, Dr. László noted. A 2013 study of 66,000 male veterans reported that widowers had nearly a 38% higher all-cause mortality risk than did married veterans.

The present study extends those findings to 490,527 patients in the Swedish Heart Failure Registry between 2000 and 2018 and/or in the Swedish Patient Register with a primary diagnosis of HF between 1987 and 2018. During a mean follow-up of 3.7 years, 12% of participants had a family member die, and 383,674 participants died.

Results showed the HF mortality risk increased 10% after the death of a child, 20% with the death of a spouse/partner, 13% with a sibling’s death, and 5% with the death of a grandchild.

No increased risk was seen after the death of a parent, which is likely owed to a median patient age of about 75 years and “is in line with our expectations of the life cycle,” Dr. László said.

An association between bereavement and mortality risk was observed in cases of loss caused by cardiovascular disease (RR, 1.34) and other natural causes (RR, 1.27) but also in cases of unnatural deaths, such as suicide (RR, 1.13).

The overall findings were similar regardless of left ventricular ejection fraction and New York Heart Association functional class and were not affected by sex or country of birth.

Dr. Russell agreed that the death of a parent would be expected among these older patients with HF but said that “if the mechanism of this truly is kind of this increased stress hormones and Takotsubo-type mechanism, you’d think it would be worse if it was your kid that died. That shocked me a bit.”

The strong association between mortality and the loss of a spouse or partner was not surprising, given that they’re an important source of mutual social support, he added.

“If it’s a 75-year-old whose spouse dies, we need to make sure that we have the children’s phone number or other people that we can reach out to and say: ‘Can you check on them?’ ” he said. “And we need to make sure that somebody else is coming in with them because I would guess that probably at least half of what patients hear in a clinic visit goes in one ear and out the other and it’s going to make that much better. So we need to find who that new support person is for the patient.”

Asked whether there are efforts underway to incorporate psychosocial factors into current U.S. guidelines, Dr. Russell replied, “certainly within heart failure, I don’t think we’re really discussing it and, that may be the best part of this paper. It really makes us think about a different way of approaching these older patients.”

Dr. László said that future studies are needed to investigate whether less severe sources of stress may also contribute to poor HF prognosis.

“In our population, 12% of patients were affected, which is quite high, but there are patients with heart failure who experience on a daily basis other sources of stress, which are less severe but chronic and affect large numbers,” she said. “This may also have important public health implications and will be an important next step.”

The authors noted that they were unable to eliminate residual confounding by genetic factors or unmeasured socioeconomic-, lifestyle-, or health-related factors shared by family members. Other limitations are limited power to detect a modest effect in some of the subanalyses and that the findings may be generalizable only to countries with social and cultural contexts and health-related factors similar to those of Sweden.

The study was supported by grants from the Swedish Council for Working Life and Social Research, the Karolinska Institutet’s Research Foundation, and the China Scholarship Council. Dr. László is also supported by a grant from the Heart and Lung Foundation. All other authors and Dr. Russell reported no relevant financial relationships.

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

The stress of losing a family member can hasten the death of patients with heart failure, suggests a large Swedish study that points to the need for greater integration of psychosocial risk factors in the treatment of HF.

The adjusted relative risk of dying was nearly 30% higher among bereaved patients with HF (1.29; 95% confidence interval, 1.27-1.30) and slightly higher for those grieving the loss of more than one family member (RR, 1.35).

The highest risk was in the first week after the loss (RR, 1.78) but persisted after 5 years of follow-up (RR, 1.30).

“Heart failure is a very difficult condition and has a very poor prognosis comparable to many, many cancers,” senior author Krisztina László, PhD, Karolinska Institutet, Stockholm, said in an interview. “So it’s important for us to be aware of these increased risks and to understand them better.”

The early risk for death could be related to stress-induced cardiomyopathy, or Takotsubo syndrome, as well as activation of the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system, and sympathetic nervous system, she explained. Higher long-term risks may reflect chronic stress, leading to poorly managed disease and an unhealthy lifestyle.

“If we understand better the underlying mechanisms maybe we can give more specific advice,” Dr. László said. “At this stage, I think having an awareness of the risk and trying to follow patients or at least not let them fall out of usual care, asking questions, trying to understand what their needs are, maybe that is what we can do well.”

A recent position paper by the European Association of Preventive Cardiology pointed out that psychosocial risk factors, like depression and social isolation, can exacerbate heart failure and calls for better integration of psychosocial factors in the treatment of patients with chronic HF.

“We don’t do a very good job of it, but I think they are very important,” observed Stuart D. Russell, MD, a professor of medicine who specializes in advanced HF at Duke University, Durham, N.C., and was not involved in the study.

“When we hear about a spouse dying, we might call and give condolences, but it’s probably a group of patients that for the next 6 months or so we need to watch more closely and see if there are things we can impact both medically as well as socially to perhaps prevent some of this increase in mortality,” he told this news organization.

Although several studies have linked bereavement with adverse health outcomes, this is just one of two studies to look specifically at its role in HF prognosis, Dr. László noted. A 2013 study of 66,000 male veterans reported that widowers had nearly a 38% higher all-cause mortality risk than did married veterans.

The present study extends those findings to 490,527 patients in the Swedish Heart Failure Registry between 2000 and 2018 and/or in the Swedish Patient Register with a primary diagnosis of HF between 1987 and 2018. During a mean follow-up of 3.7 years, 12% of participants had a family member die, and 383,674 participants died.

Results showed the HF mortality risk increased 10% after the death of a child, 20% with the death of a spouse/partner, 13% with a sibling’s death, and 5% with the death of a grandchild.

No increased risk was seen after the death of a parent, which is likely owed to a median patient age of about 75 years and “is in line with our expectations of the life cycle,” Dr. László said.

An association between bereavement and mortality risk was observed in cases of loss caused by cardiovascular disease (RR, 1.34) and other natural causes (RR, 1.27) but also in cases of unnatural deaths, such as suicide (RR, 1.13).

The overall findings were similar regardless of left ventricular ejection fraction and New York Heart Association functional class and were not affected by sex or country of birth.

Dr. Russell agreed that the death of a parent would be expected among these older patients with HF but said that “if the mechanism of this truly is kind of this increased stress hormones and Takotsubo-type mechanism, you’d think it would be worse if it was your kid that died. That shocked me a bit.”

The strong association between mortality and the loss of a spouse or partner was not surprising, given that they’re an important source of mutual social support, he added.

“If it’s a 75-year-old whose spouse dies, we need to make sure that we have the children’s phone number or other people that we can reach out to and say: ‘Can you check on them?’ ” he said. “And we need to make sure that somebody else is coming in with them because I would guess that probably at least half of what patients hear in a clinic visit goes in one ear and out the other and it’s going to make that much better. So we need to find who that new support person is for the patient.”

Asked whether there are efforts underway to incorporate psychosocial factors into current U.S. guidelines, Dr. Russell replied, “certainly within heart failure, I don’t think we’re really discussing it and, that may be the best part of this paper. It really makes us think about a different way of approaching these older patients.”

Dr. László said that future studies are needed to investigate whether less severe sources of stress may also contribute to poor HF prognosis.

“In our population, 12% of patients were affected, which is quite high, but there are patients with heart failure who experience on a daily basis other sources of stress, which are less severe but chronic and affect large numbers,” she said. “This may also have important public health implications and will be an important next step.”

The authors noted that they were unable to eliminate residual confounding by genetic factors or unmeasured socioeconomic-, lifestyle-, or health-related factors shared by family members. Other limitations are limited power to detect a modest effect in some of the subanalyses and that the findings may be generalizable only to countries with social and cultural contexts and health-related factors similar to those of Sweden.

The study was supported by grants from the Swedish Council for Working Life and Social Research, the Karolinska Institutet’s Research Foundation, and the China Scholarship Council. Dr. László is also supported by a grant from the Heart and Lung Foundation. All other authors and Dr. Russell reported no relevant financial relationships.

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

Falsely elevated pulse oximeter readings are leading to less oxygen supplementation for people of color, a recent study finds.

The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.

“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO₂ readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”

Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
 

‘We’re not providing equal care’

Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).

Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO₂ readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.

Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO₂ and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.

“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”

The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.

Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.

“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.

Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”

While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
 

Black patients 3X more likely to have hidden hypoxia than White patients

Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.

The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.

“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”

Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.

“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.

“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”

Yet Dr. Sjoding entertained the possibility that other factors may have been at play.

“I think definitely there’s a social commentary on prioritization of research,” he said.

The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.

Falsely elevated pulse oximeter readings are leading to less oxygen supplementation for people of color, a recent study finds.

The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.

“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO₂ readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”

Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
 

‘We’re not providing equal care’

Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).

Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO₂ readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.

Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO₂ and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.

“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”

The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.

Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.

“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.

Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”

While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
 

Black patients 3X more likely to have hidden hypoxia than White patients

Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.

The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.

“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”

Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.

“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.

“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”

Yet Dr. Sjoding entertained the possibility that other factors may have been at play.

“I think definitely there’s a social commentary on prioritization of research,” he said.

The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.

Falsely elevated pulse oximeter readings are leading to less oxygen supplementation for people of color, a recent study finds.

The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.

“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO₂ readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”

Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
 

‘We’re not providing equal care’

Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).

Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO₂ readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.

Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO₂ and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.

“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”

The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.

Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.

“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.

Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”

While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
 

Black patients 3X more likely to have hidden hypoxia than White patients

Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.

The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.

“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”

Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.

“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.

“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”

Yet Dr. Sjoding entertained the possibility that other factors may have been at play.

“I think definitely there’s a social commentary on prioritization of research,” he said.

The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.