Cardiology

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

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

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

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

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

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

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

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

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

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

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

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

Older adults who take part in regular weight lifting – either with or without moderate to vigorous aerobic activity – show significant reductions in all-cause and cardiovascular disease (CVD) mortality, with the strongest effects observed when the two types of exercise are combined, new research shows.

“The novel finding from our study is that weight lifting is independently associated with lower all-cause and CVD-specific mortality, regardless of aerobic activity,” first author Jessica Gorzelitz, PhD, said in an interview.

Wavebreakmedia/Getty Images

“What’s less surprising – but consistent and nonetheless noteworthy – is that weight lifting in combination with aerobic exercise provides the lowest...risk for mortality in older adults,” added Dr. Gorzelitz, an assistant professor of health promotion in the department of health and human physiology at the University of Iowa, Iowa City.

Those who undertook weight lifting and aerobic exercise in combination had around a 40% lower risk of death than those who reported no moderate to vigorous aerobic activity or weight lifting. The findings were recently published online in the British Journal of Sports Medicine.

Physical activity guidelines generally recommend regular moderate to vigorous aerobic physical activity, in addition to at least 2 days per week of muscle-strengthening exercise for all major muscle groups for adults to improve health and boost longevity.

However, few observational studies have examined the association between muscle strengthening and mortality, and even fewer have looked specifically at the benefits of weight lifting, Dr. Gorzelitz said.
 

Benefit of weight lifting stronger in women than men

To investigate, Dr. Gorzelitz and coauthors evaluated data on participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which, initiated in 1993, and involved adults aged 55-74 at 10 U.S. cancer centers.

Thirteen years into the trial, in 2006, participants completed follow-up questionnaires that included an assessment of weight lifting (not included in a baseline survey).

Among 99,713 participants involved in the current analysis, the mean age at the time of the follow-up questionnaire was 71.3 years. Participants had a mean body mass index of 27.8 kg/m² and 52.6% were women.

Only about a quarter of adults (23%) reported any weight lifting activity within the previous 12 months, with fewer, at 16%, reporting regular weight lifting of between one and six times per week.

Participants’ physical aerobic activity was also assessed. Physical activity guidelines (2018) recommend at least 150-300 minutes per week of moderate-intensity aerobic physical activity or 75-150 minutes per week of vigorous intensity aerobic activity or an equal combination of the two. Overall, 23.6% of participants reported activity that met the guideline for moderate to vigorous physical activity, and 8% exceeded it.

Over a median follow-up of about 9 years, 28,477 deaths occurred.

Those reporting weight lifting had a 9% lower risk of combined all-cause mortality and CVD mortality, after adjustment for any moderate to vigorous physical activity (each hazard ratio, 0.91).

Adults who met aerobic activity recommendations but did not weight lift had a 32% lower risk of all-cause mortality (HR, 0.68), while those who also reported weight lifting 1-2 times per week in addition to the aerobic activity had as much as a 41% lower risk of death (HR, 0.59), compared with adults reporting no moderate to vigorous aerobic activity or weight lifting.

The benefit of weight lifting in terms of cancer mortality was only observed without adjustment for moderate to vigorous physical activity, and was therefore considered null, which Dr. Gorzelitz said was somewhat surprising. “We will examine this association further because there could still be a signal there,” she said, noting other studies have shown that muscle strengthening activity is associated with lower cancer-specific mortality.

Of note, the benefit of weight lifting appeared stronger in women versus men, Dr. Gorzelitz said.
 

What are the mechanisms?

Underscoring that the results show only associations and not causation, Dr. Gorzelitz speculated that mechanisms behind a mortality benefit could include known favorable physiological changes of weight lifting.

“If people are weight lifting [to a degree] to reap strength benefits, we generally see improvement in body composition, including reductions in fat and improvements in lean tissue, and we know that those changes are associated with mortality, so it could be that the weight lifting is driving the strength or body composition,” she said.

The full body response involved in weight lifting could also play a key role, she noted.

With weight lifting, “the muscles have to redirect more blood flow, the heart is pumping harder, the lungs breathe more and when the muscles are worked in that fashion, there could be other system-wide adaptations,” she said.

Furthermore, social aspects could play a role, Dr. Gorzelitz observed.

“Unlike muscle strengthening [activities] that can be done in the home setting, weight lifting typically has to be done in recreational facilities or other community centers, and considering that this is an older adult population, that social interaction could be very key for preventing isolation.”

Important limitations include that the study did not determine the nature of the weight lifting, including the duration of the weight lifting sessions or type of weight, which could feasibly range from small hand-held weights to heavier weight lifting.

The study also couldn’t show how long participants had engaged in weight lifting in terms of months or years, hence, the duration needed to see a mortality benefit was not established.

Nevertheless, the study’s finding that the group with the lowest benefits was the one reporting no aerobic or weight lifting exercise underscores the benefits of even small amounts of exercise.

“I think it’s really important to promote the importance of adding muscle strengthening, but also of any physical activity,” Dr. Gorzelitz said. “Start small, but something is better than nothing.”

The authors reported no relevant financial relationships.

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

Older adults who take part in regular weight lifting – either with or without moderate to vigorous aerobic activity – show significant reductions in all-cause and cardiovascular disease (CVD) mortality, with the strongest effects observed when the two types of exercise are combined, new research shows.

“The novel finding from our study is that weight lifting is independently associated with lower all-cause and CVD-specific mortality, regardless of aerobic activity,” first author Jessica Gorzelitz, PhD, said in an interview.

Wavebreakmedia/Getty Images

“What’s less surprising – but consistent and nonetheless noteworthy – is that weight lifting in combination with aerobic exercise provides the lowest...risk for mortality in older adults,” added Dr. Gorzelitz, an assistant professor of health promotion in the department of health and human physiology at the University of Iowa, Iowa City.

Those who undertook weight lifting and aerobic exercise in combination had around a 40% lower risk of death than those who reported no moderate to vigorous aerobic activity or weight lifting. The findings were recently published online in the British Journal of Sports Medicine.

Physical activity guidelines generally recommend regular moderate to vigorous aerobic physical activity, in addition to at least 2 days per week of muscle-strengthening exercise for all major muscle groups for adults to improve health and boost longevity.

However, few observational studies have examined the association between muscle strengthening and mortality, and even fewer have looked specifically at the benefits of weight lifting, Dr. Gorzelitz said.
 

Benefit of weight lifting stronger in women than men

To investigate, Dr. Gorzelitz and coauthors evaluated data on participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which, initiated in 1993, and involved adults aged 55-74 at 10 U.S. cancer centers.

Thirteen years into the trial, in 2006, participants completed follow-up questionnaires that included an assessment of weight lifting (not included in a baseline survey).

Among 99,713 participants involved in the current analysis, the mean age at the time of the follow-up questionnaire was 71.3 years. Participants had a mean body mass index of 27.8 kg/m² and 52.6% were women.

Only about a quarter of adults (23%) reported any weight lifting activity within the previous 12 months, with fewer, at 16%, reporting regular weight lifting of between one and six times per week.

Participants’ physical aerobic activity was also assessed. Physical activity guidelines (2018) recommend at least 150-300 minutes per week of moderate-intensity aerobic physical activity or 75-150 minutes per week of vigorous intensity aerobic activity or an equal combination of the two. Overall, 23.6% of participants reported activity that met the guideline for moderate to vigorous physical activity, and 8% exceeded it.

Over a median follow-up of about 9 years, 28,477 deaths occurred.

Those reporting weight lifting had a 9% lower risk of combined all-cause mortality and CVD mortality, after adjustment for any moderate to vigorous physical activity (each hazard ratio, 0.91).

Adults who met aerobic activity recommendations but did not weight lift had a 32% lower risk of all-cause mortality (HR, 0.68), while those who also reported weight lifting 1-2 times per week in addition to the aerobic activity had as much as a 41% lower risk of death (HR, 0.59), compared with adults reporting no moderate to vigorous aerobic activity or weight lifting.

The benefit of weight lifting in terms of cancer mortality was only observed without adjustment for moderate to vigorous physical activity, and was therefore considered null, which Dr. Gorzelitz said was somewhat surprising. “We will examine this association further because there could still be a signal there,” she said, noting other studies have shown that muscle strengthening activity is associated with lower cancer-specific mortality.

Of note, the benefit of weight lifting appeared stronger in women versus men, Dr. Gorzelitz said.
 

What are the mechanisms?

Underscoring that the results show only associations and not causation, Dr. Gorzelitz speculated that mechanisms behind a mortality benefit could include known favorable physiological changes of weight lifting.

“If people are weight lifting [to a degree] to reap strength benefits, we generally see improvement in body composition, including reductions in fat and improvements in lean tissue, and we know that those changes are associated with mortality, so it could be that the weight lifting is driving the strength or body composition,” she said.

The full body response involved in weight lifting could also play a key role, she noted.

With weight lifting, “the muscles have to redirect more blood flow, the heart is pumping harder, the lungs breathe more and when the muscles are worked in that fashion, there could be other system-wide adaptations,” she said.

Furthermore, social aspects could play a role, Dr. Gorzelitz observed.

“Unlike muscle strengthening [activities] that can be done in the home setting, weight lifting typically has to be done in recreational facilities or other community centers, and considering that this is an older adult population, that social interaction could be very key for preventing isolation.”

Important limitations include that the study did not determine the nature of the weight lifting, including the duration of the weight lifting sessions or type of weight, which could feasibly range from small hand-held weights to heavier weight lifting.

The study also couldn’t show how long participants had engaged in weight lifting in terms of months or years, hence, the duration needed to see a mortality benefit was not established.

Nevertheless, the study’s finding that the group with the lowest benefits was the one reporting no aerobic or weight lifting exercise underscores the benefits of even small amounts of exercise.

“I think it’s really important to promote the importance of adding muscle strengthening, but also of any physical activity,” Dr. Gorzelitz said. “Start small, but something is better than nothing.”

The authors reported no relevant financial relationships.

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

Older adults who take part in regular weight lifting – either with or without moderate to vigorous aerobic activity – show significant reductions in all-cause and cardiovascular disease (CVD) mortality, with the strongest effects observed when the two types of exercise are combined, new research shows.

“The novel finding from our study is that weight lifting is independently associated with lower all-cause and CVD-specific mortality, regardless of aerobic activity,” first author Jessica Gorzelitz, PhD, said in an interview.

Wavebreakmedia/Getty Images

“What’s less surprising – but consistent and nonetheless noteworthy – is that weight lifting in combination with aerobic exercise provides the lowest...risk for mortality in older adults,” added Dr. Gorzelitz, an assistant professor of health promotion in the department of health and human physiology at the University of Iowa, Iowa City.

Those who undertook weight lifting and aerobic exercise in combination had around a 40% lower risk of death than those who reported no moderate to vigorous aerobic activity or weight lifting. The findings were recently published online in the British Journal of Sports Medicine.

Physical activity guidelines generally recommend regular moderate to vigorous aerobic physical activity, in addition to at least 2 days per week of muscle-strengthening exercise for all major muscle groups for adults to improve health and boost longevity.

However, few observational studies have examined the association between muscle strengthening and mortality, and even fewer have looked specifically at the benefits of weight lifting, Dr. Gorzelitz said.
 

Benefit of weight lifting stronger in women than men

To investigate, Dr. Gorzelitz and coauthors evaluated data on participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which, initiated in 1993, and involved adults aged 55-74 at 10 U.S. cancer centers.

Thirteen years into the trial, in 2006, participants completed follow-up questionnaires that included an assessment of weight lifting (not included in a baseline survey).

Among 99,713 participants involved in the current analysis, the mean age at the time of the follow-up questionnaire was 71.3 years. Participants had a mean body mass index of 27.8 kg/m² and 52.6% were women.

Only about a quarter of adults (23%) reported any weight lifting activity within the previous 12 months, with fewer, at 16%, reporting regular weight lifting of between one and six times per week.

Participants’ physical aerobic activity was also assessed. Physical activity guidelines (2018) recommend at least 150-300 minutes per week of moderate-intensity aerobic physical activity or 75-150 minutes per week of vigorous intensity aerobic activity or an equal combination of the two. Overall, 23.6% of participants reported activity that met the guideline for moderate to vigorous physical activity, and 8% exceeded it.

Over a median follow-up of about 9 years, 28,477 deaths occurred.

Those reporting weight lifting had a 9% lower risk of combined all-cause mortality and CVD mortality, after adjustment for any moderate to vigorous physical activity (each hazard ratio, 0.91).

Adults who met aerobic activity recommendations but did not weight lift had a 32% lower risk of all-cause mortality (HR, 0.68), while those who also reported weight lifting 1-2 times per week in addition to the aerobic activity had as much as a 41% lower risk of death (HR, 0.59), compared with adults reporting no moderate to vigorous aerobic activity or weight lifting.

The benefit of weight lifting in terms of cancer mortality was only observed without adjustment for moderate to vigorous physical activity, and was therefore considered null, which Dr. Gorzelitz said was somewhat surprising. “We will examine this association further because there could still be a signal there,” she said, noting other studies have shown that muscle strengthening activity is associated with lower cancer-specific mortality.

Of note, the benefit of weight lifting appeared stronger in women versus men, Dr. Gorzelitz said.
 

What are the mechanisms?

Underscoring that the results show only associations and not causation, Dr. Gorzelitz speculated that mechanisms behind a mortality benefit could include known favorable physiological changes of weight lifting.

“If people are weight lifting [to a degree] to reap strength benefits, we generally see improvement in body composition, including reductions in fat and improvements in lean tissue, and we know that those changes are associated with mortality, so it could be that the weight lifting is driving the strength or body composition,” she said.

The full body response involved in weight lifting could also play a key role, she noted.

With weight lifting, “the muscles have to redirect more blood flow, the heart is pumping harder, the lungs breathe more and when the muscles are worked in that fashion, there could be other system-wide adaptations,” she said.

Furthermore, social aspects could play a role, Dr. Gorzelitz observed.

“Unlike muscle strengthening [activities] that can be done in the home setting, weight lifting typically has to be done in recreational facilities or other community centers, and considering that this is an older adult population, that social interaction could be very key for preventing isolation.”

Important limitations include that the study did not determine the nature of the weight lifting, including the duration of the weight lifting sessions or type of weight, which could feasibly range from small hand-held weights to heavier weight lifting.

The study also couldn’t show how long participants had engaged in weight lifting in terms of months or years, hence, the duration needed to see a mortality benefit was not established.

Nevertheless, the study’s finding that the group with the lowest benefits was the one reporting no aerobic or weight lifting exercise underscores the benefits of even small amounts of exercise.

“I think it’s really important to promote the importance of adding muscle strengthening, but also of any physical activity,” Dr. Gorzelitz said. “Start small, but something is better than nothing.”

The authors reported no relevant financial relationships.

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

Women with preeclampsia with severe features benefit from treatment with oral nifedipine during labor and delivery, results of a randomized controlled trial suggest.

The study showed that intrapartum administration of extended-release oral nifedipine was safe and reduced the need for acute intravenous or immediate-release oral hypertensive therapy. There was a trend toward fewer cesarean deliveries and less need for neonatal intensive care.

The results suggest that providers “consider initiating long-acting nifedipine every 24 hours for individuals with preeclampsia with severe features who are undergoing induction of labor,” Erin M. Cleary, MD, with the Ohio State University, Columbus, told this news organization.

“There is no need to wait until patients require one or more doses of acute [antihypertensive] therapy before starting long-acting nifedipine, as long as they otherwise meet criteria for preeclampsia with severe features,” Dr. Cleary said.

The study was published online in Hypertension.

Clear benefits for mom and baby

Preeclampsia complicates up to 8% of pregnancies and often leads to significant maternal and perinatal morbidity.

“We know that bringing down very high blood pressure to a safer range will help prevent maternal and fetal complications. However, besides rapid-acting, intravenous medicines for severe hypertension during pregnancy, optimal management for hypertension during the labor and delivery process has not been studied,” Dr. Cleary explains in a news release.

In a randomized, triple-blind, placebo-controlled study, the researchers assessed whether treatment with long-acting nifedipine could prevent severe hypertension in women with a singleton or twin gestation and preeclampsia with severe features, as defined according to American College of Obstetrics and Gynecology criteria.

During induction of labor between 22 and 41 weeks’ gestation, 55 women were assigned to 30-mg oral extended-release nifedipine, and 55 received matching placebo, administered every 24 hours until delivery.

The primary outcome was receipt of one or more doses of acute hypertension therapy for blood pressure of at least 160/110 mm Hg that was sustained for 10 minutes or longer.

The primary outcome occurred in significantly fewer women in the nifedipine group than in the placebo group (34% vs. 55%; relative risk, 0.62; 95% CI, 0.39-0.97; number needed to treat, 4.7).

Fewer women in the nifedipine group than in the placebo group required cesarean delivery, although this difference did not meet statistical significance (21% vs. 35%; RR, 0.60; 95% CI, 0.31-1.15).

There was no between-group difference in the rate of hypotensive episodes, including symptomatic hypotension requiring phenylephrine for pressure support following neuraxial anesthesia (9.4% vs. 8.2%; RR, 1.15; 95% CI, 0.33-4.06).

After delivery, there was no difference in the rate of persistently severe blood pressure that required acute therapy and maintenance therapy at time of discharge home.

Birth weight and rates of births of neonates who were small for gestational age were similar in the two groups. There was a trend for decreased rates of neonatal intensive care unit admission among infants born to mothers who received nifedipine (29% vs. 47%; RR, 0.62; 95% CI, 0.37-1.02).

The neonatal composite outcome was also similar between the nifedipine group and the placebo group (36% vs. 41%; RR, 0.83; 95% CI, 0.51-1.37). The composite outcome included Apgar score of less than 7 at 5 minutes, hyperbilirubinemia requiring phototherapy, hypoglycemia requiring intravenous therapy, or supplemental oxygen therapy beyond the first 24 hours of life.

“Our findings support the growing trend in more active management of hypertension in pregnancy with daily maintenance medications,” Dr. Cleary and colleagues note in their article.

“Even in the absence of preeclampsia, emerging research suggests pregnant individuals may benefit from initiating and titrating antihypertensive therapy at goals similar to the nonobstetric population,” they add.

Potentially practice changing

Reached for comment, Vesna Garovic, MD, PhD, with Mayo Clinic, Rochester, Minn., said that this is an “important initial paper to start a very important conversation about blood pressure treatment goals in preeclampsia.”

Dr. Garovic noted that for chronic hypertension in pregnancy, the blood pressure treatment goal is now less than or equal to 140/90 mm Hg.

“However, this does not apply to preeclampsia, where quite high blood pressures, such 160/110 mm Hg or higher, are still allowed before treatment is considered,” Dr. Garovic said.

“This study shows that as soon as you reach that level, treatment with oral nifedipine should be initiated and that timely initiation of oral nifedipine may optimize blood pressure control and decrease the need for intravenous therapy subsequently, and that has good effects on the mother without adversely affecting the baby,” Dr. Garovic said.

“This is potentially practice changing,” Dr. Garovic added. “But the elephant in the room is the question of why we are waiting for blood pressure to reach such dangerous levels before initiating treatment, and whether initiating treatment at a blood pressure of 140/90 or higher may prevent blood pressure reaching these high levels and women developing complications that are the consequence of severe hypertension.”

The study was funded by the Ohio State University’s Department of Obstetrics and Gynecology. Dr. Cleary and Dr. Garovic have disclosed no relevant financial relationships.

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

Women with preeclampsia with severe features benefit from treatment with oral nifedipine during labor and delivery, results of a randomized controlled trial suggest.

The study showed that intrapartum administration of extended-release oral nifedipine was safe and reduced the need for acute intravenous or immediate-release oral hypertensive therapy. There was a trend toward fewer cesarean deliveries and less need for neonatal intensive care.

The results suggest that providers “consider initiating long-acting nifedipine every 24 hours for individuals with preeclampsia with severe features who are undergoing induction of labor,” Erin M. Cleary, MD, with the Ohio State University, Columbus, told this news organization.

“There is no need to wait until patients require one or more doses of acute [antihypertensive] therapy before starting long-acting nifedipine, as long as they otherwise meet criteria for preeclampsia with severe features,” Dr. Cleary said.

The study was published online in Hypertension.

Clear benefits for mom and baby

Preeclampsia complicates up to 8% of pregnancies and often leads to significant maternal and perinatal morbidity.

“We know that bringing down very high blood pressure to a safer range will help prevent maternal and fetal complications. However, besides rapid-acting, intravenous medicines for severe hypertension during pregnancy, optimal management for hypertension during the labor and delivery process has not been studied,” Dr. Cleary explains in a news release.

In a randomized, triple-blind, placebo-controlled study, the researchers assessed whether treatment with long-acting nifedipine could prevent severe hypertension in women with a singleton or twin gestation and preeclampsia with severe features, as defined according to American College of Obstetrics and Gynecology criteria.

During induction of labor between 22 and 41 weeks’ gestation, 55 women were assigned to 30-mg oral extended-release nifedipine, and 55 received matching placebo, administered every 24 hours until delivery.

The primary outcome was receipt of one or more doses of acute hypertension therapy for blood pressure of at least 160/110 mm Hg that was sustained for 10 minutes or longer.

The primary outcome occurred in significantly fewer women in the nifedipine group than in the placebo group (34% vs. 55%; relative risk, 0.62; 95% CI, 0.39-0.97; number needed to treat, 4.7).

Fewer women in the nifedipine group than in the placebo group required cesarean delivery, although this difference did not meet statistical significance (21% vs. 35%; RR, 0.60; 95% CI, 0.31-1.15).

There was no between-group difference in the rate of hypotensive episodes, including symptomatic hypotension requiring phenylephrine for pressure support following neuraxial anesthesia (9.4% vs. 8.2%; RR, 1.15; 95% CI, 0.33-4.06).

After delivery, there was no difference in the rate of persistently severe blood pressure that required acute therapy and maintenance therapy at time of discharge home.

Birth weight and rates of births of neonates who were small for gestational age were similar in the two groups. There was a trend for decreased rates of neonatal intensive care unit admission among infants born to mothers who received nifedipine (29% vs. 47%; RR, 0.62; 95% CI, 0.37-1.02).

The neonatal composite outcome was also similar between the nifedipine group and the placebo group (36% vs. 41%; RR, 0.83; 95% CI, 0.51-1.37). The composite outcome included Apgar score of less than 7 at 5 minutes, hyperbilirubinemia requiring phototherapy, hypoglycemia requiring intravenous therapy, or supplemental oxygen therapy beyond the first 24 hours of life.

“Our findings support the growing trend in more active management of hypertension in pregnancy with daily maintenance medications,” Dr. Cleary and colleagues note in their article.

“Even in the absence of preeclampsia, emerging research suggests pregnant individuals may benefit from initiating and titrating antihypertensive therapy at goals similar to the nonobstetric population,” they add.

Potentially practice changing

Reached for comment, Vesna Garovic, MD, PhD, with Mayo Clinic, Rochester, Minn., said that this is an “important initial paper to start a very important conversation about blood pressure treatment goals in preeclampsia.”

Dr. Garovic noted that for chronic hypertension in pregnancy, the blood pressure treatment goal is now less than or equal to 140/90 mm Hg.

“However, this does not apply to preeclampsia, where quite high blood pressures, such 160/110 mm Hg or higher, are still allowed before treatment is considered,” Dr. Garovic said.

“This study shows that as soon as you reach that level, treatment with oral nifedipine should be initiated and that timely initiation of oral nifedipine may optimize blood pressure control and decrease the need for intravenous therapy subsequently, and that has good effects on the mother without adversely affecting the baby,” Dr. Garovic said.

“This is potentially practice changing,” Dr. Garovic added. “But the elephant in the room is the question of why we are waiting for blood pressure to reach such dangerous levels before initiating treatment, and whether initiating treatment at a blood pressure of 140/90 or higher may prevent blood pressure reaching these high levels and women developing complications that are the consequence of severe hypertension.”

The study was funded by the Ohio State University’s Department of Obstetrics and Gynecology. Dr. Cleary and Dr. Garovic have disclosed no relevant financial relationships.

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

Women with preeclampsia with severe features benefit from treatment with oral nifedipine during labor and delivery, results of a randomized controlled trial suggest.

The study showed that intrapartum administration of extended-release oral nifedipine was safe and reduced the need for acute intravenous or immediate-release oral hypertensive therapy. There was a trend toward fewer cesarean deliveries and less need for neonatal intensive care.

The results suggest that providers “consider initiating long-acting nifedipine every 24 hours for individuals with preeclampsia with severe features who are undergoing induction of labor,” Erin M. Cleary, MD, with the Ohio State University, Columbus, told this news organization.

“There is no need to wait until patients require one or more doses of acute [antihypertensive] therapy before starting long-acting nifedipine, as long as they otherwise meet criteria for preeclampsia with severe features,” Dr. Cleary said.

The study was published online in Hypertension.

Clear benefits for mom and baby

Preeclampsia complicates up to 8% of pregnancies and often leads to significant maternal and perinatal morbidity.

“We know that bringing down very high blood pressure to a safer range will help prevent maternal and fetal complications. However, besides rapid-acting, intravenous medicines for severe hypertension during pregnancy, optimal management for hypertension during the labor and delivery process has not been studied,” Dr. Cleary explains in a news release.

In a randomized, triple-blind, placebo-controlled study, the researchers assessed whether treatment with long-acting nifedipine could prevent severe hypertension in women with a singleton or twin gestation and preeclampsia with severe features, as defined according to American College of Obstetrics and Gynecology criteria.

During induction of labor between 22 and 41 weeks’ gestation, 55 women were assigned to 30-mg oral extended-release nifedipine, and 55 received matching placebo, administered every 24 hours until delivery.

The primary outcome was receipt of one or more doses of acute hypertension therapy for blood pressure of at least 160/110 mm Hg that was sustained for 10 minutes or longer.

The primary outcome occurred in significantly fewer women in the nifedipine group than in the placebo group (34% vs. 55%; relative risk, 0.62; 95% CI, 0.39-0.97; number needed to treat, 4.7).

Fewer women in the nifedipine group than in the placebo group required cesarean delivery, although this difference did not meet statistical significance (21% vs. 35%; RR, 0.60; 95% CI, 0.31-1.15).

There was no between-group difference in the rate of hypotensive episodes, including symptomatic hypotension requiring phenylephrine for pressure support following neuraxial anesthesia (9.4% vs. 8.2%; RR, 1.15; 95% CI, 0.33-4.06).

After delivery, there was no difference in the rate of persistently severe blood pressure that required acute therapy and maintenance therapy at time of discharge home.

Birth weight and rates of births of neonates who were small for gestational age were similar in the two groups. There was a trend for decreased rates of neonatal intensive care unit admission among infants born to mothers who received nifedipine (29% vs. 47%; RR, 0.62; 95% CI, 0.37-1.02).

The neonatal composite outcome was also similar between the nifedipine group and the placebo group (36% vs. 41%; RR, 0.83; 95% CI, 0.51-1.37). The composite outcome included Apgar score of less than 7 at 5 minutes, hyperbilirubinemia requiring phototherapy, hypoglycemia requiring intravenous therapy, or supplemental oxygen therapy beyond the first 24 hours of life.

“Our findings support the growing trend in more active management of hypertension in pregnancy with daily maintenance medications,” Dr. Cleary and colleagues note in their article.

“Even in the absence of preeclampsia, emerging research suggests pregnant individuals may benefit from initiating and titrating antihypertensive therapy at goals similar to the nonobstetric population,” they add.

Potentially practice changing

Reached for comment, Vesna Garovic, MD, PhD, with Mayo Clinic, Rochester, Minn., said that this is an “important initial paper to start a very important conversation about blood pressure treatment goals in preeclampsia.”

Dr. Garovic noted that for chronic hypertension in pregnancy, the blood pressure treatment goal is now less than or equal to 140/90 mm Hg.

“However, this does not apply to preeclampsia, where quite high blood pressures, such 160/110 mm Hg or higher, are still allowed before treatment is considered,” Dr. Garovic said.

“This study shows that as soon as you reach that level, treatment with oral nifedipine should be initiated and that timely initiation of oral nifedipine may optimize blood pressure control and decrease the need for intravenous therapy subsequently, and that has good effects on the mother without adversely affecting the baby,” Dr. Garovic said.

“This is potentially practice changing,” Dr. Garovic added. “But the elephant in the room is the question of why we are waiting for blood pressure to reach such dangerous levels before initiating treatment, and whether initiating treatment at a blood pressure of 140/90 or higher may prevent blood pressure reaching these high levels and women developing complications that are the consequence of severe hypertension.”

The study was funded by the Ohio State University’s Department of Obstetrics and Gynecology. Dr. Cleary and Dr. Garovic have disclosed no relevant financial relationships.

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

Long-term antidepressant use is tied to an increased risk of adverse outcomes, including cardiovascular disease (CVD), cerebrovascular disease, coronary heart disease (CHD), and all-cause mortality, new research suggests.

The investigators drew on 10-year data from the UK Biobank on over 220,000 adults and compared the risk of developing adverse health outcomes among those taking antidepressants with the risk among those who were not taking antidepressants.

After adjusting for preexisting risk factors, they found that 10-year antidepressant use was associated with a twofold higher risk of CHD, an almost-twofold higher risk of CVD as well as CVD mortality, a higher risk of cerebrovascular disease, and more than double the risk of all-cause mortality.

On the other hand, at 10 years, antidepressant use was associated with a 23% lower risk of developing hypertension and a 32% lower risk of diabetes.

The main culprits were mirtazapine, venlafaxine, duloxetine, and trazodone, although SSRIs were also tied to increased risk.

“Our message for clinicians is that prescribing of antidepressants in the long term may not be harm free [and] we hope that this study will help doctors and patients have more informed conversations when they weigh up the potential risks and benefits of treatments for depression,” study investigator Narinder Bansal, MD, honorary research fellow, Centre for Academic Health and Centre for Academic Primary Care, University of Bristol (England), said in a news release.

“Regardless of whether the drugs are the underlying cause of these problems, our findings emphasize the importance of proactive cardiovascular monitoring and prevention in patients who have depression and are on antidepressants, given that both have been associated with higher risks,” she added.

The study was published online in the British Journal of Psychiatry Open.
 

Monitoring of CVD risk ‘critical’

Antidepressants are among the most widely prescribed drugs; 70 million prescriptions were dispensed in 2018 alone, representing a doubling of prescriptions for these agents in a decade, the investigators noted. “This striking rise in prescribing is attributed to long-term treatment rather than an increased incidence of depression.”

Most trials that have assessed antidepressant efficacy have been “poorly suited to examining adverse outcomes.” One reason for this is that many of the trials are short-term studies. Since depression is “strongly associated” with CVD risk factors, “careful assessment of the long-term cardiometabolic effects of antidepressant treatment is critical.”

Moreover, information about “a wide range of prospectively measured confounders ... is needed to provide robust estimates of the risks associated with long-term antidepressant use,” the authors noted.

The researchers examined the association between antidepressant use and four cardiometabolic morbidity outcomes – diabetes, hypertension, cerebrovascular disease, and CHD. In addition, they assessed two mortality outcomes – CVD mortality and all-cause mortality. Participants were divided into cohorts on the basis of outcome of interest.

The dataset contains detailed information on socioeconomic status, demographics, anthropometric, behavioral, and biochemical risk factors, disability, and health status and is linked to datasets of primary care records and deaths.

The study included 222,121 participants whose data had been linked to primary care records during 2018 (median age of participants, 56-57 years). About half were women, and 96% were of White ethnicity.

Participants were excluded if they had been prescribed antidepressants 12 months or less before baseline, if they had previously been diagnosed for the outcome of interest, if they had been previously prescribed psychotropic drugs, if they used cardiometabolic drugs at baseline, or if they had undergone treatment with antidepressant polytherapy.

Potential confounders included age, gender, body mass index, waist/hip ratio, smoking and alcohol intake status, physical activity, parental history of outcome, biochemical and hematologic biomarkers, socioeconomic status, and long-term illness, disability, or infirmity.
 

Mechanism unclear

By the end of the 5- and 10-year follow-up periods, an average of 8% and 6% of participants in each cohort, respectively, had been prescribed an antidepressant. SSRIs constituted the most commonly prescribed class (80%-82%), and citalopram was the most commonly prescribed SSRI (46%-47%). Mirtazapine was the most frequently prescribed non-SSRI antidepressant (44%-46%).

At 5 years, any antidepressant use was associated with an increased risk for diabetes, CHD, and all-cause mortality, but the findings were attenuated after further adjustment for confounders. In fact, SSRIs were associated with a reduced risk of diabetes at 5 years (hazard ratio, 0.64; 95% confidence interval, 0.49-0.83).

At 10 years, SSRIs were associated with an increased risk of cerebrovascular disease, CVD mortality, and all-cause mortality; non-SSRIs were associated with an increased risk of CHD, CVD, and all-cause mortality.

On the other hand, SSRIs were associated with a decrease in risk of diabetes and hypertension at 10 years (HR, 0.68; 95% CI, 0.53-0.87; and HR, 0.77; 95% CI, 0.66-0.89, respectively).

“While we have taken into account a wide range of pre-existing risk factors for cardiovascular disease, including those that are linked to depression such as excess weight, smoking, and low physical activity, it is difficult to fully control for the effects of depression in this kind of study, partly because there is considerable variability in the recording of depression severity in primary care,” said Dr. Bansal.

“This is important because many people taking antidepressants such as mirtazapine, venlafaxine, duloxetine and trazodone may have a more severe depression. This makes it difficult to fully separate the effects of the depression from the effects of medication,” she said.

Further research “is needed to assess whether the associations we have seen are genuinely due to the drugs; and, if so, why this might be,” she added.
 

Strengths, limitations

Commenting on the study, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit at the University of Toronto,, discussed the strengths and weaknesses of the study.

The UK Biobank is a “well-described, well-phenotyped dataset of good quality,” said Dr. McIntyre, chairperson and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study. Another strength is the “impressive number of variables the database contains, which enabled the authors to go much deeper into the topics.”

A “significant limitation” is the confounding that is inherent to the disorder itself – “people with depression have a much higher intrinsic risk of CVD, [cerebrovascular disease], and cardiovascular mortality,” Dr. McIntyre noted.

The researchers did not adjust for trauma or childhood maltreatment, “which are the biggest risk factors for both depression and CVD; and drug and alcohol misuse were also not accounted for.”

Additionally, “to determine whether something is an association or potentially causative, it must satisfy the Bradford-Hill criteria,” said Dr. McIntyre. “Since we’re moving more toward using these big databases and because we depend on them to give us long-term perspectives, we would want to see coherent, compelling Bradford-Hill criteria regarding causation. If you don’t have any, that’s fine too, but then it’s important to make clear that there is no clear causative line, just an association.”

The research was funded by the National Institute of Health Research School for Primary Care Research and was supported by the NI Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. Dr. McIntyre has received research grant support from CI/GACD/National Natural Science Foundation of China and the Milken Institute and speaker/consultation fees from numerous companies. Dr. McIntyre is a CEO of Braxia Scientific.

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

Long-term antidepressant use is tied to an increased risk of adverse outcomes, including cardiovascular disease (CVD), cerebrovascular disease, coronary heart disease (CHD), and all-cause mortality, new research suggests.

The investigators drew on 10-year data from the UK Biobank on over 220,000 adults and compared the risk of developing adverse health outcomes among those taking antidepressants with the risk among those who were not taking antidepressants.

After adjusting for preexisting risk factors, they found that 10-year antidepressant use was associated with a twofold higher risk of CHD, an almost-twofold higher risk of CVD as well as CVD mortality, a higher risk of cerebrovascular disease, and more than double the risk of all-cause mortality.

On the other hand, at 10 years, antidepressant use was associated with a 23% lower risk of developing hypertension and a 32% lower risk of diabetes.

The main culprits were mirtazapine, venlafaxine, duloxetine, and trazodone, although SSRIs were also tied to increased risk.

“Our message for clinicians is that prescribing of antidepressants in the long term may not be harm free [and] we hope that this study will help doctors and patients have more informed conversations when they weigh up the potential risks and benefits of treatments for depression,” study investigator Narinder Bansal, MD, honorary research fellow, Centre for Academic Health and Centre for Academic Primary Care, University of Bristol (England), said in a news release.

“Regardless of whether the drugs are the underlying cause of these problems, our findings emphasize the importance of proactive cardiovascular monitoring and prevention in patients who have depression and are on antidepressants, given that both have been associated with higher risks,” she added.

The study was published online in the British Journal of Psychiatry Open.
 

Monitoring of CVD risk ‘critical’

Antidepressants are among the most widely prescribed drugs; 70 million prescriptions were dispensed in 2018 alone, representing a doubling of prescriptions for these agents in a decade, the investigators noted. “This striking rise in prescribing is attributed to long-term treatment rather than an increased incidence of depression.”

Most trials that have assessed antidepressant efficacy have been “poorly suited to examining adverse outcomes.” One reason for this is that many of the trials are short-term studies. Since depression is “strongly associated” with CVD risk factors, “careful assessment of the long-term cardiometabolic effects of antidepressant treatment is critical.”

Moreover, information about “a wide range of prospectively measured confounders ... is needed to provide robust estimates of the risks associated with long-term antidepressant use,” the authors noted.

The researchers examined the association between antidepressant use and four cardiometabolic morbidity outcomes – diabetes, hypertension, cerebrovascular disease, and CHD. In addition, they assessed two mortality outcomes – CVD mortality and all-cause mortality. Participants were divided into cohorts on the basis of outcome of interest.

The dataset contains detailed information on socioeconomic status, demographics, anthropometric, behavioral, and biochemical risk factors, disability, and health status and is linked to datasets of primary care records and deaths.

The study included 222,121 participants whose data had been linked to primary care records during 2018 (median age of participants, 56-57 years). About half were women, and 96% were of White ethnicity.

Participants were excluded if they had been prescribed antidepressants 12 months or less before baseline, if they had previously been diagnosed for the outcome of interest, if they had been previously prescribed psychotropic drugs, if they used cardiometabolic drugs at baseline, or if they had undergone treatment with antidepressant polytherapy.

Potential confounders included age, gender, body mass index, waist/hip ratio, smoking and alcohol intake status, physical activity, parental history of outcome, biochemical and hematologic biomarkers, socioeconomic status, and long-term illness, disability, or infirmity.
 

Mechanism unclear

By the end of the 5- and 10-year follow-up periods, an average of 8% and 6% of participants in each cohort, respectively, had been prescribed an antidepressant. SSRIs constituted the most commonly prescribed class (80%-82%), and citalopram was the most commonly prescribed SSRI (46%-47%). Mirtazapine was the most frequently prescribed non-SSRI antidepressant (44%-46%).

At 5 years, any antidepressant use was associated with an increased risk for diabetes, CHD, and all-cause mortality, but the findings were attenuated after further adjustment for confounders. In fact, SSRIs were associated with a reduced risk of diabetes at 5 years (hazard ratio, 0.64; 95% confidence interval, 0.49-0.83).

At 10 years, SSRIs were associated with an increased risk of cerebrovascular disease, CVD mortality, and all-cause mortality; non-SSRIs were associated with an increased risk of CHD, CVD, and all-cause mortality.

On the other hand, SSRIs were associated with a decrease in risk of diabetes and hypertension at 10 years (HR, 0.68; 95% CI, 0.53-0.87; and HR, 0.77; 95% CI, 0.66-0.89, respectively).

“While we have taken into account a wide range of pre-existing risk factors for cardiovascular disease, including those that are linked to depression such as excess weight, smoking, and low physical activity, it is difficult to fully control for the effects of depression in this kind of study, partly because there is considerable variability in the recording of depression severity in primary care,” said Dr. Bansal.

“This is important because many people taking antidepressants such as mirtazapine, venlafaxine, duloxetine and trazodone may have a more severe depression. This makes it difficult to fully separate the effects of the depression from the effects of medication,” she said.

Further research “is needed to assess whether the associations we have seen are genuinely due to the drugs; and, if so, why this might be,” she added.
 

Strengths, limitations

Commenting on the study, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit at the University of Toronto,, discussed the strengths and weaknesses of the study.

The UK Biobank is a “well-described, well-phenotyped dataset of good quality,” said Dr. McIntyre, chairperson and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study. Another strength is the “impressive number of variables the database contains, which enabled the authors to go much deeper into the topics.”

A “significant limitation” is the confounding that is inherent to the disorder itself – “people with depression have a much higher intrinsic risk of CVD, [cerebrovascular disease], and cardiovascular mortality,” Dr. McIntyre noted.

The researchers did not adjust for trauma or childhood maltreatment, “which are the biggest risk factors for both depression and CVD; and drug and alcohol misuse were also not accounted for.”

Additionally, “to determine whether something is an association or potentially causative, it must satisfy the Bradford-Hill criteria,” said Dr. McIntyre. “Since we’re moving more toward using these big databases and because we depend on them to give us long-term perspectives, we would want to see coherent, compelling Bradford-Hill criteria regarding causation. If you don’t have any, that’s fine too, but then it’s important to make clear that there is no clear causative line, just an association.”

The research was funded by the National Institute of Health Research School for Primary Care Research and was supported by the NI Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. Dr. McIntyre has received research grant support from CI/GACD/National Natural Science Foundation of China and the Milken Institute and speaker/consultation fees from numerous companies. Dr. McIntyre is a CEO of Braxia Scientific.

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

Long-term antidepressant use is tied to an increased risk of adverse outcomes, including cardiovascular disease (CVD), cerebrovascular disease, coronary heart disease (CHD), and all-cause mortality, new research suggests.

The investigators drew on 10-year data from the UK Biobank on over 220,000 adults and compared the risk of developing adverse health outcomes among those taking antidepressants with the risk among those who were not taking antidepressants.

After adjusting for preexisting risk factors, they found that 10-year antidepressant use was associated with a twofold higher risk of CHD, an almost-twofold higher risk of CVD as well as CVD mortality, a higher risk of cerebrovascular disease, and more than double the risk of all-cause mortality.

On the other hand, at 10 years, antidepressant use was associated with a 23% lower risk of developing hypertension and a 32% lower risk of diabetes.

The main culprits were mirtazapine, venlafaxine, duloxetine, and trazodone, although SSRIs were also tied to increased risk.

“Our message for clinicians is that prescribing of antidepressants in the long term may not be harm free [and] we hope that this study will help doctors and patients have more informed conversations when they weigh up the potential risks and benefits of treatments for depression,” study investigator Narinder Bansal, MD, honorary research fellow, Centre for Academic Health and Centre for Academic Primary Care, University of Bristol (England), said in a news release.

“Regardless of whether the drugs are the underlying cause of these problems, our findings emphasize the importance of proactive cardiovascular monitoring and prevention in patients who have depression and are on antidepressants, given that both have been associated with higher risks,” she added.

The study was published online in the British Journal of Psychiatry Open.
 

Monitoring of CVD risk ‘critical’

Antidepressants are among the most widely prescribed drugs; 70 million prescriptions were dispensed in 2018 alone, representing a doubling of prescriptions for these agents in a decade, the investigators noted. “This striking rise in prescribing is attributed to long-term treatment rather than an increased incidence of depression.”

Most trials that have assessed antidepressant efficacy have been “poorly suited to examining adverse outcomes.” One reason for this is that many of the trials are short-term studies. Since depression is “strongly associated” with CVD risk factors, “careful assessment of the long-term cardiometabolic effects of antidepressant treatment is critical.”

Moreover, information about “a wide range of prospectively measured confounders ... is needed to provide robust estimates of the risks associated with long-term antidepressant use,” the authors noted.

The researchers examined the association between antidepressant use and four cardiometabolic morbidity outcomes – diabetes, hypertension, cerebrovascular disease, and CHD. In addition, they assessed two mortality outcomes – CVD mortality and all-cause mortality. Participants were divided into cohorts on the basis of outcome of interest.

The dataset contains detailed information on socioeconomic status, demographics, anthropometric, behavioral, and biochemical risk factors, disability, and health status and is linked to datasets of primary care records and deaths.

The study included 222,121 participants whose data had been linked to primary care records during 2018 (median age of participants, 56-57 years). About half were women, and 96% were of White ethnicity.

Participants were excluded if they had been prescribed antidepressants 12 months or less before baseline, if they had previously been diagnosed for the outcome of interest, if they had been previously prescribed psychotropic drugs, if they used cardiometabolic drugs at baseline, or if they had undergone treatment with antidepressant polytherapy.

Potential confounders included age, gender, body mass index, waist/hip ratio, smoking and alcohol intake status, physical activity, parental history of outcome, biochemical and hematologic biomarkers, socioeconomic status, and long-term illness, disability, or infirmity.
 

Mechanism unclear

By the end of the 5- and 10-year follow-up periods, an average of 8% and 6% of participants in each cohort, respectively, had been prescribed an antidepressant. SSRIs constituted the most commonly prescribed class (80%-82%), and citalopram was the most commonly prescribed SSRI (46%-47%). Mirtazapine was the most frequently prescribed non-SSRI antidepressant (44%-46%).

At 5 years, any antidepressant use was associated with an increased risk for diabetes, CHD, and all-cause mortality, but the findings were attenuated after further adjustment for confounders. In fact, SSRIs were associated with a reduced risk of diabetes at 5 years (hazard ratio, 0.64; 95% confidence interval, 0.49-0.83).

At 10 years, SSRIs were associated with an increased risk of cerebrovascular disease, CVD mortality, and all-cause mortality; non-SSRIs were associated with an increased risk of CHD, CVD, and all-cause mortality.

On the other hand, SSRIs were associated with a decrease in risk of diabetes and hypertension at 10 years (HR, 0.68; 95% CI, 0.53-0.87; and HR, 0.77; 95% CI, 0.66-0.89, respectively).

“While we have taken into account a wide range of pre-existing risk factors for cardiovascular disease, including those that are linked to depression such as excess weight, smoking, and low physical activity, it is difficult to fully control for the effects of depression in this kind of study, partly because there is considerable variability in the recording of depression severity in primary care,” said Dr. Bansal.

“This is important because many people taking antidepressants such as mirtazapine, venlafaxine, duloxetine and trazodone may have a more severe depression. This makes it difficult to fully separate the effects of the depression from the effects of medication,” she said.

Further research “is needed to assess whether the associations we have seen are genuinely due to the drugs; and, if so, why this might be,” she added.
 

Strengths, limitations

Commenting on the study, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit at the University of Toronto,, discussed the strengths and weaknesses of the study.

The UK Biobank is a “well-described, well-phenotyped dataset of good quality,” said Dr. McIntyre, chairperson and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study. Another strength is the “impressive number of variables the database contains, which enabled the authors to go much deeper into the topics.”

A “significant limitation” is the confounding that is inherent to the disorder itself – “people with depression have a much higher intrinsic risk of CVD, [cerebrovascular disease], and cardiovascular mortality,” Dr. McIntyre noted.

The researchers did not adjust for trauma or childhood maltreatment, “which are the biggest risk factors for both depression and CVD; and drug and alcohol misuse were also not accounted for.”

Additionally, “to determine whether something is an association or potentially causative, it must satisfy the Bradford-Hill criteria,” said Dr. McIntyre. “Since we’re moving more toward using these big databases and because we depend on them to give us long-term perspectives, we would want to see coherent, compelling Bradford-Hill criteria regarding causation. If you don’t have any, that’s fine too, but then it’s important to make clear that there is no clear causative line, just an association.”

The research was funded by the National Institute of Health Research School for Primary Care Research and was supported by the NI Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. Dr. McIntyre has received research grant support from CI/GACD/National Natural Science Foundation of China and the Milken Institute and speaker/consultation fees from numerous companies. Dr. McIntyre is a CEO of Braxia Scientific.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

Cardiovascular disease (CVD) and mortality risk could be detected by routine retinal scanning, according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)–Norfolk study.

The researchers, from St. George’s University of London, Cambridge University, Kingston University, Moorfields Eye Hospital, and University College London, developed a method of artificial intelligence (AI)–enabled imaging of the retina’s vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.

The system “paves the way for a highly effective, noninvasive screening test for people at medium to high risk of circulatory disease that doesn’t have to be done in a clinic,” they said. “In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.” Optometry specialists welcomed the prospect and hailed it as “an exciting development.”
 

Retinal vessels give an accurate early indicator of CVD

The study, published online in the British Journal of Ophthalmology, was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren’t always reliable in identifying people who will go on to develop or die of circulatory diseases. 

The researchers developed a fully automated AI-enabled algorithm, called Quantitative Analysis of Retinal vessels Topology and Size (QUARTZ), to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40-69 years, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.

They then applied these models to the retinal images of 7,411 participants, aged 48-92 years, in the EPIC-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.

The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age, 56.8 years) and 201 circulatory deaths among 5,862 EPIC-Norfolk participants (average age, 67.6 years).
 

Vessel characteristics important predictors of CVD mortality

Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction.

Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or MI) as well as retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk, the authors said. 

Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women. However, the team said that, while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler noninvasive risk score based on age, sex, smoking status, medical history, and RV “yielded comparable performance to FRS, without the need for blood sampling or BP measurement.”
 

Vasculometry low cost, noninvasive and with high street availability

They concluded: “Retinal imaging is established within clinic and hospital eye care and in optometric practices in the U.S. and U.K. AI-enabled vasculometry risk prediction is fully automated, low cost, noninvasive and has the potential for reaching a higher proportion of the population in the community because of “high street” availability and because blood sampling or sphygmomanometry are not needed.

“[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke, compared with MI, which is more macrovascular, except perhaps in women. 

“In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.”

In the United Kingdom, for example, it could be included in the primary care NHS Health Check for those aged 41-74 years, they suggested.  In addition, “high street” retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. “This would offer a novel approach to identify those at high risk of circulatory mortality, which is not currently screened for,” the team said.
 

Test could help to identify high-risk individuals

In a linked editorial, Ify Mordi, MD, and Emanuele Trucco, MD, of the University of Dundee (Scotland), said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all U.K. deaths – and its burden is increasing. “Identification of individuals at high risk is particularly important,” they said, but current clinical risk scores to identify those at risk “are unfortunately not perfect,” so miss some of those who might benefit from preventative therapy.

“The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information.” In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.

“The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine.” However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening program and who would act on the findings?

The editorial concluded: “What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimize clinical work flows and enable practical implementation in routine practice.”
 

‘Exciting development that could improve outcomes’

Asked to comment, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: “This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it’s an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients.”

She added: “Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.

“We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces.” 

The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.

A version of this article first appeared on Medscape UK.

Cardiovascular disease (CVD) and mortality risk could be detected by routine retinal scanning, according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)–Norfolk study.

The researchers, from St. George’s University of London, Cambridge University, Kingston University, Moorfields Eye Hospital, and University College London, developed a method of artificial intelligence (AI)–enabled imaging of the retina’s vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.

The system “paves the way for a highly effective, noninvasive screening test for people at medium to high risk of circulatory disease that doesn’t have to be done in a clinic,” they said. “In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.” Optometry specialists welcomed the prospect and hailed it as “an exciting development.”
 

Retinal vessels give an accurate early indicator of CVD

The study, published online in the British Journal of Ophthalmology, was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren’t always reliable in identifying people who will go on to develop or die of circulatory diseases. 

The researchers developed a fully automated AI-enabled algorithm, called Quantitative Analysis of Retinal vessels Topology and Size (QUARTZ), to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40-69 years, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.

They then applied these models to the retinal images of 7,411 participants, aged 48-92 years, in the EPIC-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.

The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age, 56.8 years) and 201 circulatory deaths among 5,862 EPIC-Norfolk participants (average age, 67.6 years).
 

Vessel characteristics important predictors of CVD mortality

Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction.

Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or MI) as well as retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk, the authors said. 

Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women. However, the team said that, while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler noninvasive risk score based on age, sex, smoking status, medical history, and RV “yielded comparable performance to FRS, without the need for blood sampling or BP measurement.”
 

Vasculometry low cost, noninvasive and with high street availability

They concluded: “Retinal imaging is established within clinic and hospital eye care and in optometric practices in the U.S. and U.K. AI-enabled vasculometry risk prediction is fully automated, low cost, noninvasive and has the potential for reaching a higher proportion of the population in the community because of “high street” availability and because blood sampling or sphygmomanometry are not needed.

“[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke, compared with MI, which is more macrovascular, except perhaps in women. 

“In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.”

In the United Kingdom, for example, it could be included in the primary care NHS Health Check for those aged 41-74 years, they suggested.  In addition, “high street” retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. “This would offer a novel approach to identify those at high risk of circulatory mortality, which is not currently screened for,” the team said.
 

Test could help to identify high-risk individuals

In a linked editorial, Ify Mordi, MD, and Emanuele Trucco, MD, of the University of Dundee (Scotland), said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all U.K. deaths – and its burden is increasing. “Identification of individuals at high risk is particularly important,” they said, but current clinical risk scores to identify those at risk “are unfortunately not perfect,” so miss some of those who might benefit from preventative therapy.

“The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information.” In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.

“The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine.” However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening program and who would act on the findings?

The editorial concluded: “What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimize clinical work flows and enable practical implementation in routine practice.”
 

‘Exciting development that could improve outcomes’

Asked to comment, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: “This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it’s an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients.”

She added: “Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.

“We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces.” 

The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.

A version of this article first appeared on Medscape UK.

Cardiovascular disease (CVD) and mortality risk could be detected by routine retinal scanning, according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)–Norfolk study.

The researchers, from St. George’s University of London, Cambridge University, Kingston University, Moorfields Eye Hospital, and University College London, developed a method of artificial intelligence (AI)–enabled imaging of the retina’s vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.

The system “paves the way for a highly effective, noninvasive screening test for people at medium to high risk of circulatory disease that doesn’t have to be done in a clinic,” they said. “In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.” Optometry specialists welcomed the prospect and hailed it as “an exciting development.”
 

Retinal vessels give an accurate early indicator of CVD

The study, published online in the British Journal of Ophthalmology, was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren’t always reliable in identifying people who will go on to develop or die of circulatory diseases. 

The researchers developed a fully automated AI-enabled algorithm, called Quantitative Analysis of Retinal vessels Topology and Size (QUARTZ), to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40-69 years, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.

They then applied these models to the retinal images of 7,411 participants, aged 48-92 years, in the EPIC-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.

The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age, 56.8 years) and 201 circulatory deaths among 5,862 EPIC-Norfolk participants (average age, 67.6 years).
 

Vessel characteristics important predictors of CVD mortality

Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction.

Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or MI) as well as retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk, the authors said. 

Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women. However, the team said that, while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler noninvasive risk score based on age, sex, smoking status, medical history, and RV “yielded comparable performance to FRS, without the need for blood sampling or BP measurement.”
 

Vasculometry low cost, noninvasive and with high street availability

They concluded: “Retinal imaging is established within clinic and hospital eye care and in optometric practices in the U.S. and U.K. AI-enabled vasculometry risk prediction is fully automated, low cost, noninvasive and has the potential for reaching a higher proportion of the population in the community because of “high street” availability and because blood sampling or sphygmomanometry are not needed.

“[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke, compared with MI, which is more macrovascular, except perhaps in women. 

“In the general population it could be used as a noncontact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention.”

In the United Kingdom, for example, it could be included in the primary care NHS Health Check for those aged 41-74 years, they suggested.  In addition, “high street” retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. “This would offer a novel approach to identify those at high risk of circulatory mortality, which is not currently screened for,” the team said.
 

Test could help to identify high-risk individuals

In a linked editorial, Ify Mordi, MD, and Emanuele Trucco, MD, of the University of Dundee (Scotland), said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all U.K. deaths – and its burden is increasing. “Identification of individuals at high risk is particularly important,” they said, but current clinical risk scores to identify those at risk “are unfortunately not perfect,” so miss some of those who might benefit from preventative therapy.

“The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information.” In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.

“The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine.” However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening program and who would act on the findings?

The editorial concluded: “What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimize clinical work flows and enable practical implementation in routine practice.”
 

‘Exciting development that could improve outcomes’

Asked to comment, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: “This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it’s an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients.”

She added: “Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.

“We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces.” 

The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.

A version of this article first appeared on Medscape UK.

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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