Cardiology News

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

Contemporary guidelines highly recommend patients with heart failure with reduced ejection fraction (HFrEF) be on all four drug classes that together have shown clinical clout, including improved survival, in major randomized trials.

Although many such patients don’t receive all four drug classes, the more that are prescribed to those with primary-prevention implantable defibrillators (ICD), the better their odds of survival, a new analysis suggests.

The cohort study of almost 5,000 patients with HFrEF and such devices saw their all-cause mortality risk improve stepwise with each additional prescription they were given toward the full quadruple drug combo at the core of modern HFrEF guideline-directed medical therapy (GDMT). The four classes are sodium-glucose cotransporter 2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and renin-angiotensin system (RAS) inhibitors.

That inverse relation between risk and number of GDMT medications held whether patients had solo-ICD or defibrillating cardiac resynchronization therapy (CRT-D) implants, and were independent of device-implantation year and comorbidities, regardless of HFrEF etiology.

“If anybody had doubts about really pushing forward as much of these guideline-directed medical therapies as the patient tolerates, these data confirm that, by doing so, we definitely do better than with two medications or one medication,” Samir Saba, MD, University of Pittsburgh Medical Center, said in an interview.

The analysis begs an old and challenging question: Do primary-prevention ICDs confer clinically important survival gains over those provided by increasingly life-preserving recommended HFrEF medical therapy?

Given the study’s incremental survival bumps with each added GDMT med, “one ought to consider whether ICD therapy can still have an impact on overall survival in this population,” proposes a report published online in JACC Clinical Electrophysiology, with Dr. Saba as senior author.

In the adjusted analysis, the 2-year risk for death from any cause in HFrEF patients with primary-prevention devices fell 36% in those with ICDs and 30% in those with CRT-D devices for each added prescribed GDMT drug, from none up to either three or four such agents (P < .001 in both cases).

Only so much can be made of nonrandomized study results, Saba observed in an interview. But they are enough to justify asking whether primary-prevention ICDs are “still valuable” in HFrEF given current GDMT. One interpretation of the study, the published report noted, is that contemporary GDMT improves HFrEF survival so much that it eclipses any such benefit from a primary-prevention ICD.

Both defibrillators and the four core drug therapies boost survival in such cases, “so the fundamental question is, are they additive. Do we save more lives by having a defibrillator on top of the medications, or is it overlapping?” Dr. Saba asked. “We don’t know the answer.”

For now, at least, the findings could reassure clinicians as they consider whether to recommended a primary-prevention ICD when there might be reasons not to, as long there is full GDMT on board, “especially what we today define as quadruple guideline-directed medical therapy.”

Recently announced North American guidelines defining an HFrEF quadruple regimen prefer – beyond a beta-blocker, MRA, and SGLT2 inhibitor – that the selected RAS inhibitor be sacubitril/valsartan (Entresto, Novartis), with ACE inhibitors or angiotensin-receptor blockers (ARBs) as a substitute, if needed.  

Nearly identical European guidelines on HFrEF quad therapy, unveiled in 2021, include but do not necessarily prefer sacubitril/valsartan over ACE inhibitors as the RAS inhibitor of choice.
 

GDMT a moving target

Primary-prevention defibrillators entered practice at a time when expected background GDMT consisted of beta-blockers and either ACE inhibitors or ARBs, the current report notes. In practice, many patients receive the devices without both drug classes optimally on board. Moreover, many who otherwise meet guidelines for such ICDs won’t tolerate the kind of maximally tolerated GDMT used in the major primary-prevention device trials.

Yet current guidelines give such devices a class I recommendation, based on the highest level of evidence, in HFrEF patients who remain symptomatic despite quad GDMT, observed Gregg C. Fonarow, MD, University of California Los Angeles Medical Center.

The current analysis “further reinforces the importance of providing all four foundational GDMTs” to all eligible HFrEF patients without contraindications who can tolerate them, he said in an interview. Such quad therapy “is associated with incremental 1-year survival advantages” in patients with primary-prevention devices. And in the major trials, “there were reductions in sudden deaths, as well as progressive heart failure deaths.”

But the current study also suggests that in practice “very few patients can actually get to all four drugs on GDMT,” Roderick Tung, MD, University of Arizona, Phoenix, said in an interview. Optimized GDMT in randomized trials probably represents the best-case scenario. “There is a difference between randomized data and real-world data, which is why we need both.”

And it asserts that “the more GDMT you’re on, the better you do,” he said. “But does that obviate the need for an ICD? I think that’s not clear,” in part because of potential confounding in the analysis. For example, patients who can take all four agents tend to be less sick than those who cannot.

“The ones who can get up to four are preselected, because they’re healthier,” Dr. Tung said. “There are real limitations – such as metabolic disturbances, acute kidney injury and cardiorenal syndrome, and hypotension – that actually make it difficult to initiate and titrate these medications.”

Indeed, the major primary-prevention ICD trials usually excluded the sickest patients with the most comorbidities, Dr. Saba observed, which raises issues about their relevance to clinical practice. But his group’s study controlled for many potential confounders by adjusting for, among other things, Elixhauser comorbidity score, ejection fraction, type of cardiomyopathy, and year of device implantation.

“We tried to level the playing field that way, to see if – despite all of this adjustment – the incremental number of heart failure medicines stills make a difference,” Dr. Saba said. “And our results suggest that yes, they still do.”
 

GDMT coverage in the real world

The analysis of patients with HFrEF involved 3,210 with ICD-only implants and 1,762 with CRT-D devices for primary prevention at a major medical center from 2010 to 2021. Of the total, 5% had not been prescribed any of the four GDMT agents, 20% had been prescribed only one, 52% were prescribed two, and 23% were prescribed three or four. Only 113 patients had been prescribed SGLT2 inhibitors, which have only recently been indicated for HFrEF.

Adjusted hazard ratios for death from any cause at 2 years for each added GDMT drug (P < .001 in each case), were 0.64 (95% confidence interval, 0.56-0.74) for ICD recipients, 0.70 (95% CI, 0.58-0.86) for those with a CRT-D device, 0.70 (95% CI, 0.60-0.81) for those with ischemic cardiomyopathy, and 0.61 (95% CI, 0.51-0.73) for patients with nonischemic disease.

The results “raise questions rather than answers,” Dr. Saba said. “At some point, someone will need to take patients who are optimized on their heart failure medications and then randomize them to defibrillator versus no defibrillator to see whether there is still an additive impact.”

Current best evidence suggests that primary-prevention ICDs in patients with guideline-based indications confer benefits that far outweigh any risks. But if the major primary-prevention ICD trials were to be repeated in patients on contemporary quad-therapy GDMT, Dr. Tung said, “would the benefit of ICD be attenuated? I think most of us believe it likely would.”

Still, he said, a background of modern GDMT could potentially “optimize” such trials by attenuating mortality from heart failure progression and thereby expanding the proportion of deaths that are arrhythmic, “which the defibrillator can prevent.”

Dr. Saba discloses receiving research support from Boston Scientific and Abbott; and serving on advisory boards for Medtronic and Boston Scientific. The other authors reported no relevant relationships. Dr. Tung has disclosed receiving speaker fees from Abbott and Boston Scientific. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.

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

Contemporary guidelines highly recommend patients with heart failure with reduced ejection fraction (HFrEF) be on all four drug classes that together have shown clinical clout, including improved survival, in major randomized trials.

Although many such patients don’t receive all four drug classes, the more that are prescribed to those with primary-prevention implantable defibrillators (ICD), the better their odds of survival, a new analysis suggests.

The cohort study of almost 5,000 patients with HFrEF and such devices saw their all-cause mortality risk improve stepwise with each additional prescription they were given toward the full quadruple drug combo at the core of modern HFrEF guideline-directed medical therapy (GDMT). The four classes are sodium-glucose cotransporter 2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and renin-angiotensin system (RAS) inhibitors.

That inverse relation between risk and number of GDMT medications held whether patients had solo-ICD or defibrillating cardiac resynchronization therapy (CRT-D) implants, and were independent of device-implantation year and comorbidities, regardless of HFrEF etiology.

“If anybody had doubts about really pushing forward as much of these guideline-directed medical therapies as the patient tolerates, these data confirm that, by doing so, we definitely do better than with two medications or one medication,” Samir Saba, MD, University of Pittsburgh Medical Center, said in an interview.

The analysis begs an old and challenging question: Do primary-prevention ICDs confer clinically important survival gains over those provided by increasingly life-preserving recommended HFrEF medical therapy?

Given the study’s incremental survival bumps with each added GDMT med, “one ought to consider whether ICD therapy can still have an impact on overall survival in this population,” proposes a report published online in JACC Clinical Electrophysiology, with Dr. Saba as senior author.

In the adjusted analysis, the 2-year risk for death from any cause in HFrEF patients with primary-prevention devices fell 36% in those with ICDs and 30% in those with CRT-D devices for each added prescribed GDMT drug, from none up to either three or four such agents (P < .001 in both cases).

Only so much can be made of nonrandomized study results, Saba observed in an interview. But they are enough to justify asking whether primary-prevention ICDs are “still valuable” in HFrEF given current GDMT. One interpretation of the study, the published report noted, is that contemporary GDMT improves HFrEF survival so much that it eclipses any such benefit from a primary-prevention ICD.

Both defibrillators and the four core drug therapies boost survival in such cases, “so the fundamental question is, are they additive. Do we save more lives by having a defibrillator on top of the medications, or is it overlapping?” Dr. Saba asked. “We don’t know the answer.”

For now, at least, the findings could reassure clinicians as they consider whether to recommended a primary-prevention ICD when there might be reasons not to, as long there is full GDMT on board, “especially what we today define as quadruple guideline-directed medical therapy.”

Recently announced North American guidelines defining an HFrEF quadruple regimen prefer – beyond a beta-blocker, MRA, and SGLT2 inhibitor – that the selected RAS inhibitor be sacubitril/valsartan (Entresto, Novartis), with ACE inhibitors or angiotensin-receptor blockers (ARBs) as a substitute, if needed.  

Nearly identical European guidelines on HFrEF quad therapy, unveiled in 2021, include but do not necessarily prefer sacubitril/valsartan over ACE inhibitors as the RAS inhibitor of choice.
 

GDMT a moving target

Primary-prevention defibrillators entered practice at a time when expected background GDMT consisted of beta-blockers and either ACE inhibitors or ARBs, the current report notes. In practice, many patients receive the devices without both drug classes optimally on board. Moreover, many who otherwise meet guidelines for such ICDs won’t tolerate the kind of maximally tolerated GDMT used in the major primary-prevention device trials.

Yet current guidelines give such devices a class I recommendation, based on the highest level of evidence, in HFrEF patients who remain symptomatic despite quad GDMT, observed Gregg C. Fonarow, MD, University of California Los Angeles Medical Center.

The current analysis “further reinforces the importance of providing all four foundational GDMTs” to all eligible HFrEF patients without contraindications who can tolerate them, he said in an interview. Such quad therapy “is associated with incremental 1-year survival advantages” in patients with primary-prevention devices. And in the major trials, “there were reductions in sudden deaths, as well as progressive heart failure deaths.”

But the current study also suggests that in practice “very few patients can actually get to all four drugs on GDMT,” Roderick Tung, MD, University of Arizona, Phoenix, said in an interview. Optimized GDMT in randomized trials probably represents the best-case scenario. “There is a difference between randomized data and real-world data, which is why we need both.”

And it asserts that “the more GDMT you’re on, the better you do,” he said. “But does that obviate the need for an ICD? I think that’s not clear,” in part because of potential confounding in the analysis. For example, patients who can take all four agents tend to be less sick than those who cannot.

“The ones who can get up to four are preselected, because they’re healthier,” Dr. Tung said. “There are real limitations – such as metabolic disturbances, acute kidney injury and cardiorenal syndrome, and hypotension – that actually make it difficult to initiate and titrate these medications.”

Indeed, the major primary-prevention ICD trials usually excluded the sickest patients with the most comorbidities, Dr. Saba observed, which raises issues about their relevance to clinical practice. But his group’s study controlled for many potential confounders by adjusting for, among other things, Elixhauser comorbidity score, ejection fraction, type of cardiomyopathy, and year of device implantation.

“We tried to level the playing field that way, to see if – despite all of this adjustment – the incremental number of heart failure medicines stills make a difference,” Dr. Saba said. “And our results suggest that yes, they still do.”
 

GDMT coverage in the real world

The analysis of patients with HFrEF involved 3,210 with ICD-only implants and 1,762 with CRT-D devices for primary prevention at a major medical center from 2010 to 2021. Of the total, 5% had not been prescribed any of the four GDMT agents, 20% had been prescribed only one, 52% were prescribed two, and 23% were prescribed three or four. Only 113 patients had been prescribed SGLT2 inhibitors, which have only recently been indicated for HFrEF.

Adjusted hazard ratios for death from any cause at 2 years for each added GDMT drug (P < .001 in each case), were 0.64 (95% confidence interval, 0.56-0.74) for ICD recipients, 0.70 (95% CI, 0.58-0.86) for those with a CRT-D device, 0.70 (95% CI, 0.60-0.81) for those with ischemic cardiomyopathy, and 0.61 (95% CI, 0.51-0.73) for patients with nonischemic disease.

The results “raise questions rather than answers,” Dr. Saba said. “At some point, someone will need to take patients who are optimized on their heart failure medications and then randomize them to defibrillator versus no defibrillator to see whether there is still an additive impact.”

Current best evidence suggests that primary-prevention ICDs in patients with guideline-based indications confer benefits that far outweigh any risks. But if the major primary-prevention ICD trials were to be repeated in patients on contemporary quad-therapy GDMT, Dr. Tung said, “would the benefit of ICD be attenuated? I think most of us believe it likely would.”

Still, he said, a background of modern GDMT could potentially “optimize” such trials by attenuating mortality from heart failure progression and thereby expanding the proportion of deaths that are arrhythmic, “which the defibrillator can prevent.”

Dr. Saba discloses receiving research support from Boston Scientific and Abbott; and serving on advisory boards for Medtronic and Boston Scientific. The other authors reported no relevant relationships. Dr. Tung has disclosed receiving speaker fees from Abbott and Boston Scientific. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.

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

Contemporary guidelines highly recommend patients with heart failure with reduced ejection fraction (HFrEF) be on all four drug classes that together have shown clinical clout, including improved survival, in major randomized trials.

Although many such patients don’t receive all four drug classes, the more that are prescribed to those with primary-prevention implantable defibrillators (ICD), the better their odds of survival, a new analysis suggests.

The cohort study of almost 5,000 patients with HFrEF and such devices saw their all-cause mortality risk improve stepwise with each additional prescription they were given toward the full quadruple drug combo at the core of modern HFrEF guideline-directed medical therapy (GDMT). The four classes are sodium-glucose cotransporter 2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and renin-angiotensin system (RAS) inhibitors.

That inverse relation between risk and number of GDMT medications held whether patients had solo-ICD or defibrillating cardiac resynchronization therapy (CRT-D) implants, and were independent of device-implantation year and comorbidities, regardless of HFrEF etiology.

“If anybody had doubts about really pushing forward as much of these guideline-directed medical therapies as the patient tolerates, these data confirm that, by doing so, we definitely do better than with two medications or one medication,” Samir Saba, MD, University of Pittsburgh Medical Center, said in an interview.

The analysis begs an old and challenging question: Do primary-prevention ICDs confer clinically important survival gains over those provided by increasingly life-preserving recommended HFrEF medical therapy?

Given the study’s incremental survival bumps with each added GDMT med, “one ought to consider whether ICD therapy can still have an impact on overall survival in this population,” proposes a report published online in JACC Clinical Electrophysiology, with Dr. Saba as senior author.

In the adjusted analysis, the 2-year risk for death from any cause in HFrEF patients with primary-prevention devices fell 36% in those with ICDs and 30% in those with CRT-D devices for each added prescribed GDMT drug, from none up to either three or four such agents (P < .001 in both cases).

Only so much can be made of nonrandomized study results, Saba observed in an interview. But they are enough to justify asking whether primary-prevention ICDs are “still valuable” in HFrEF given current GDMT. One interpretation of the study, the published report noted, is that contemporary GDMT improves HFrEF survival so much that it eclipses any such benefit from a primary-prevention ICD.

Both defibrillators and the four core drug therapies boost survival in such cases, “so the fundamental question is, are they additive. Do we save more lives by having a defibrillator on top of the medications, or is it overlapping?” Dr. Saba asked. “We don’t know the answer.”

For now, at least, the findings could reassure clinicians as they consider whether to recommended a primary-prevention ICD when there might be reasons not to, as long there is full GDMT on board, “especially what we today define as quadruple guideline-directed medical therapy.”

Recently announced North American guidelines defining an HFrEF quadruple regimen prefer – beyond a beta-blocker, MRA, and SGLT2 inhibitor – that the selected RAS inhibitor be sacubitril/valsartan (Entresto, Novartis), with ACE inhibitors or angiotensin-receptor blockers (ARBs) as a substitute, if needed.  

Nearly identical European guidelines on HFrEF quad therapy, unveiled in 2021, include but do not necessarily prefer sacubitril/valsartan over ACE inhibitors as the RAS inhibitor of choice.
 

GDMT a moving target

Primary-prevention defibrillators entered practice at a time when expected background GDMT consisted of beta-blockers and either ACE inhibitors or ARBs, the current report notes. In practice, many patients receive the devices without both drug classes optimally on board. Moreover, many who otherwise meet guidelines for such ICDs won’t tolerate the kind of maximally tolerated GDMT used in the major primary-prevention device trials.

Yet current guidelines give such devices a class I recommendation, based on the highest level of evidence, in HFrEF patients who remain symptomatic despite quad GDMT, observed Gregg C. Fonarow, MD, University of California Los Angeles Medical Center.

The current analysis “further reinforces the importance of providing all four foundational GDMTs” to all eligible HFrEF patients without contraindications who can tolerate them, he said in an interview. Such quad therapy “is associated with incremental 1-year survival advantages” in patients with primary-prevention devices. And in the major trials, “there were reductions in sudden deaths, as well as progressive heart failure deaths.”

But the current study also suggests that in practice “very few patients can actually get to all four drugs on GDMT,” Roderick Tung, MD, University of Arizona, Phoenix, said in an interview. Optimized GDMT in randomized trials probably represents the best-case scenario. “There is a difference between randomized data and real-world data, which is why we need both.”

And it asserts that “the more GDMT you’re on, the better you do,” he said. “But does that obviate the need for an ICD? I think that’s not clear,” in part because of potential confounding in the analysis. For example, patients who can take all four agents tend to be less sick than those who cannot.

“The ones who can get up to four are preselected, because they’re healthier,” Dr. Tung said. “There are real limitations – such as metabolic disturbances, acute kidney injury and cardiorenal syndrome, and hypotension – that actually make it difficult to initiate and titrate these medications.”

Indeed, the major primary-prevention ICD trials usually excluded the sickest patients with the most comorbidities, Dr. Saba observed, which raises issues about their relevance to clinical practice. But his group’s study controlled for many potential confounders by adjusting for, among other things, Elixhauser comorbidity score, ejection fraction, type of cardiomyopathy, and year of device implantation.

“We tried to level the playing field that way, to see if – despite all of this adjustment – the incremental number of heart failure medicines stills make a difference,” Dr. Saba said. “And our results suggest that yes, they still do.”
 

GDMT coverage in the real world

The analysis of patients with HFrEF involved 3,210 with ICD-only implants and 1,762 with CRT-D devices for primary prevention at a major medical center from 2010 to 2021. Of the total, 5% had not been prescribed any of the four GDMT agents, 20% had been prescribed only one, 52% were prescribed two, and 23% were prescribed three or four. Only 113 patients had been prescribed SGLT2 inhibitors, which have only recently been indicated for HFrEF.

Adjusted hazard ratios for death from any cause at 2 years for each added GDMT drug (P < .001 in each case), were 0.64 (95% confidence interval, 0.56-0.74) for ICD recipients, 0.70 (95% CI, 0.58-0.86) for those with a CRT-D device, 0.70 (95% CI, 0.60-0.81) for those with ischemic cardiomyopathy, and 0.61 (95% CI, 0.51-0.73) for patients with nonischemic disease.

The results “raise questions rather than answers,” Dr. Saba said. “At some point, someone will need to take patients who are optimized on their heart failure medications and then randomize them to defibrillator versus no defibrillator to see whether there is still an additive impact.”

Current best evidence suggests that primary-prevention ICDs in patients with guideline-based indications confer benefits that far outweigh any risks. But if the major primary-prevention ICD trials were to be repeated in patients on contemporary quad-therapy GDMT, Dr. Tung said, “would the benefit of ICD be attenuated? I think most of us believe it likely would.”

Still, he said, a background of modern GDMT could potentially “optimize” such trials by attenuating mortality from heart failure progression and thereby expanding the proportion of deaths that are arrhythmic, “which the defibrillator can prevent.”

Dr. Saba discloses receiving research support from Boston Scientific and Abbott; and serving on advisory boards for Medtronic and Boston Scientific. The other authors reported no relevant relationships. Dr. Tung has disclosed receiving speaker fees from Abbott and Boston Scientific. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.

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

For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.

But a new study published  in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.

“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.

M. Alexander Otto/MDedge News

Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.

The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.

Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.

Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.

At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.

“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.

At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.

The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,

Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.

Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.

“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.

“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”

Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.

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

For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.

But a new study published  in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.

“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.

M. Alexander Otto/MDedge News

Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.

The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.

Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.

Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.

At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.

“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.

At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.

The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,

Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.

Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.

“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.

“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”

Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.

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

For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.

But a new study published  in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.

“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.

M. Alexander Otto/MDedge News

Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.

The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.

Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.

Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.

At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.

“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.

At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.

The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,

Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.

Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.

“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.

“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”

Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Top-line results released on July 26 from the RADIANCE II trial show the Paradise ultrasound renal denervation system significantly reduces daytime ambulatory systolic blood pressure, compared with a sham procedure at 2 months in patients with mild to moderate uncontrolled hypertension.

The trial was conducted in 224 patients who were previously treated with up to two medications and were randomized while off medication at more than 60 centers in 8 countries. No further details or results were provided.

The pivotal RADIANCE II trial, required for FDA approval, is the third and largest randomized, sham-controlled study following positive results reported by RADIANCE-HTN SOLO and RADIANCE-HTN TRIO, ReCor Medical and its subsidiary Otsuka Medical Devices noted in the announcement.

The field of renal denervation fell out of favor after the largest trial in 535 patients, SYMPLICITY HTN-3, failed to show a significant reduction in systolic blood pressure at 6 months, compared with sham control in resistant hypertension.

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

Top-line results released on July 26 from the RADIANCE II trial show the Paradise ultrasound renal denervation system significantly reduces daytime ambulatory systolic blood pressure, compared with a sham procedure at 2 months in patients with mild to moderate uncontrolled hypertension.

The trial was conducted in 224 patients who were previously treated with up to two medications and were randomized while off medication at more than 60 centers in 8 countries. No further details or results were provided.

The pivotal RADIANCE II trial, required for FDA approval, is the third and largest randomized, sham-controlled study following positive results reported by RADIANCE-HTN SOLO and RADIANCE-HTN TRIO, ReCor Medical and its subsidiary Otsuka Medical Devices noted in the announcement.

The field of renal denervation fell out of favor after the largest trial in 535 patients, SYMPLICITY HTN-3, failed to show a significant reduction in systolic blood pressure at 6 months, compared with sham control in resistant hypertension.

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

Top-line results released on July 26 from the RADIANCE II trial show the Paradise ultrasound renal denervation system significantly reduces daytime ambulatory systolic blood pressure, compared with a sham procedure at 2 months in patients with mild to moderate uncontrolled hypertension.

The trial was conducted in 224 patients who were previously treated with up to two medications and were randomized while off medication at more than 60 centers in 8 countries. No further details or results were provided.

The pivotal RADIANCE II trial, required for FDA approval, is the third and largest randomized, sham-controlled study following positive results reported by RADIANCE-HTN SOLO and RADIANCE-HTN TRIO, ReCor Medical and its subsidiary Otsuka Medical Devices noted in the announcement.

The field of renal denervation fell out of favor after the largest trial in 535 patients, SYMPLICITY HTN-3, failed to show a significant reduction in systolic blood pressure at 6 months, compared with sham control in resistant hypertension.

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

Exercise in a pill? Sign us up

You just got home from a long shift and you know you should go to the gym, but the bed is calling and you just answered. We know sometimes we have to make sacrifices in the name of fitness, but there just aren’t enough hours in the day. Unless our prayers have been answered. There could be a pill that has the benefits of working out without having to work out.

In a study published in Nature, investigators reported that they have identified a molecule made during exercise and used it on mice, which took in less food after being given the pill, which may open doors to understanding how exercise affects hunger.

©Rido/Fotolia.com

Gonorrhea and grandparents: A match made in prehistoric heaven

*Editorial note: LOTME takes no responsibility for any unfortunate imagery the reader may have experienced from the above headline.

Old people are the greatest. Back pains, cognitive decline, aches in all the diodes down your left side, there’s nothing quite like your golden years. Notably, however, humans are one of the few animals who experience true old age, as most creatures are adapted to maximize reproductive potential. As such, living past menopause is rare in the animal kingdom.

CDC/John Martin Jr.

This is where the “grandmother hypothesis” comes in: Back in Ye Olde Stone Age, women who lived into old age could provide child care for younger women, because human babies require a lot more time and attention than other animal offspring. But how did humans end up living so long? Enter a group of Californian researchers, who believe they have an answer. It was gonorrhea.

When compared with the chimpanzee genome (as well as with Neanderthals and Denisovans, our closest ancestors), humans have a unique mutated version of the CD33 gene that lacks a sugar-binding site; the standard version uses the sugar-binding site to protect against autoimmune response in the body, but that same site actually suppresses the brain’s ability to clear away damaged brain cells and amyloid, which eventually leads to diseases like dementia. The mutated version allows microglia (brain immune cells) to attack and clear out this unwanted material. People with higher levels of this mutated CD33 variant actually have higher protection against Alzheimer’s.

Interestingly, gonorrhea bacteria are coated in the same sugar that standard CD33 receptors bind to, thus allowing them to bypass the body’s immune system. According to the researchers, the mutated CD33 version likely emerged as a protection against gonorrhea, depriving the bacteria of their “molecular mimicry” abilities. In one of life’s happy accidents, it turned out this mutation also protects against age-related diseases, thus allowing humans with the mutation to live longer. Obviously, this was a good thing, and we ran with it until the modern day. Now we have senior citizens climbing Everest, and all our politicians keep on politicking into their 70s and 80s ... well, everything has its drawbacks.
 

Parents raise a glass to children’s food addiction

There can be something pretty addicting about processed foods. Have you ever eaten just one french fry? Or taken just one cookie? If so, your willpower is incredible. For many of us, it can be a struggle to stop.

© Aleksandr Stennikov/Fotolia.com

A recent study from the University of Michigan, which considered the existence of an eating phenotype, suggests our parents’ habits could be to blame.

By administering a series of questionnaires that inquired about food addiction, alcohol use disorders, cannabis use disorder, nicotine/e-cigarette dependence, and their family tree, investigators found that participants with a “paternal history of problematic alcohol use” had higher risk of food addiction but not obesity.

Apparently about one in five people display a clinically significant addiction to highly processed foods. It was noted that foods like ice cream, pizza, and french fries have high amounts of refined carbs and fats, which could trigger an addictive response.

Lindzey Hoover, a graduate student at the university who was the study’s lead author, noted that living in an environment where these foods are cheap and accessible can be really challenging for those with a family history of addiction. The investigators suggested that public health approaches, like restriction of other substances and marketing to kids, should be put in place for highly processed foods.

Maybe french fries should come with a warning label.
 

A prescription for America’s traffic problems

Nostalgia is a funny thing. Do you ever feel nostalgic about things that really weren’t very pleasant in the first place? Take, for instance, the morning commute. Here in the Washington area, more than 2 years into the COVID era, the traffic is still not what it used to be … and we kind of miss it.

PhotoDisk

Nah, not really. That was just a way to get everyone thinking about driving, because AAA has something of an explanation for the situation out there on the highways and byways of America. It’s drugs. No, not those kinds of drugs. This time it’s prescription drugs that are the problem. Well, part of the problem, anyway.

AAA did a survey last summer and found that nearly 50% of drivers “used one or more potentially impairing medications in the past 30 days. … The proportion of those choosing to drive is higher among those taking multiple medications.” How much higher? More than 63% of those with two or more prescriptions were driving within 2 hours of taking at least one of those meds, as were 71% of those taking three or more.

The 2,657 respondents also were asked about the types of potentially impairing drugs they were taking: 61% of those using antidepressants had been on the road within 2 hours of use at least once in the past 30 days, as had 73% of those taking an amphetamine, AAA said.

So there you have it. That guy in the BMW who’s been tailgating you for the last 3 miles? He may be a jerk, but there’s a good chance he’s a jerk with a prescription … or two … or three.

Exercise in a pill? Sign us up

You just got home from a long shift and you know you should go to the gym, but the bed is calling and you just answered. We know sometimes we have to make sacrifices in the name of fitness, but there just aren’t enough hours in the day. Unless our prayers have been answered. There could be a pill that has the benefits of working out without having to work out.

In a study published in Nature, investigators reported that they have identified a molecule made during exercise and used it on mice, which took in less food after being given the pill, which may open doors to understanding how exercise affects hunger.

©Rido/Fotolia.com

Gonorrhea and grandparents: A match made in prehistoric heaven

*Editorial note: LOTME takes no responsibility for any unfortunate imagery the reader may have experienced from the above headline.

Old people are the greatest. Back pains, cognitive decline, aches in all the diodes down your left side, there’s nothing quite like your golden years. Notably, however, humans are one of the few animals who experience true old age, as most creatures are adapted to maximize reproductive potential. As such, living past menopause is rare in the animal kingdom.

CDC/John Martin Jr.

This is where the “grandmother hypothesis” comes in: Back in Ye Olde Stone Age, women who lived into old age could provide child care for younger women, because human babies require a lot more time and attention than other animal offspring. But how did humans end up living so long? Enter a group of Californian researchers, who believe they have an answer. It was gonorrhea.

When compared with the chimpanzee genome (as well as with Neanderthals and Denisovans, our closest ancestors), humans have a unique mutated version of the CD33 gene that lacks a sugar-binding site; the standard version uses the sugar-binding site to protect against autoimmune response in the body, but that same site actually suppresses the brain’s ability to clear away damaged brain cells and amyloid, which eventually leads to diseases like dementia. The mutated version allows microglia (brain immune cells) to attack and clear out this unwanted material. People with higher levels of this mutated CD33 variant actually have higher protection against Alzheimer’s.

Interestingly, gonorrhea bacteria are coated in the same sugar that standard CD33 receptors bind to, thus allowing them to bypass the body’s immune system. According to the researchers, the mutated CD33 version likely emerged as a protection against gonorrhea, depriving the bacteria of their “molecular mimicry” abilities. In one of life’s happy accidents, it turned out this mutation also protects against age-related diseases, thus allowing humans with the mutation to live longer. Obviously, this was a good thing, and we ran with it until the modern day. Now we have senior citizens climbing Everest, and all our politicians keep on politicking into their 70s and 80s ... well, everything has its drawbacks.
 

Parents raise a glass to children’s food addiction

There can be something pretty addicting about processed foods. Have you ever eaten just one french fry? Or taken just one cookie? If so, your willpower is incredible. For many of us, it can be a struggle to stop.

© Aleksandr Stennikov/Fotolia.com

A recent study from the University of Michigan, which considered the existence of an eating phenotype, suggests our parents’ habits could be to blame.

By administering a series of questionnaires that inquired about food addiction, alcohol use disorders, cannabis use disorder, nicotine/e-cigarette dependence, and their family tree, investigators found that participants with a “paternal history of problematic alcohol use” had higher risk of food addiction but not obesity.

Apparently about one in five people display a clinically significant addiction to highly processed foods. It was noted that foods like ice cream, pizza, and french fries have high amounts of refined carbs and fats, which could trigger an addictive response.

Lindzey Hoover, a graduate student at the university who was the study’s lead author, noted that living in an environment where these foods are cheap and accessible can be really challenging for those with a family history of addiction. The investigators suggested that public health approaches, like restriction of other substances and marketing to kids, should be put in place for highly processed foods.

Maybe french fries should come with a warning label.
 

A prescription for America’s traffic problems

Nostalgia is a funny thing. Do you ever feel nostalgic about things that really weren’t very pleasant in the first place? Take, for instance, the morning commute. Here in the Washington area, more than 2 years into the COVID era, the traffic is still not what it used to be … and we kind of miss it.

PhotoDisk

Nah, not really. That was just a way to get everyone thinking about driving, because AAA has something of an explanation for the situation out there on the highways and byways of America. It’s drugs. No, not those kinds of drugs. This time it’s prescription drugs that are the problem. Well, part of the problem, anyway.

AAA did a survey last summer and found that nearly 50% of drivers “used one or more potentially impairing medications in the past 30 days. … The proportion of those choosing to drive is higher among those taking multiple medications.” How much higher? More than 63% of those with two or more prescriptions were driving within 2 hours of taking at least one of those meds, as were 71% of those taking three or more.

The 2,657 respondents also were asked about the types of potentially impairing drugs they were taking: 61% of those using antidepressants had been on the road within 2 hours of use at least once in the past 30 days, as had 73% of those taking an amphetamine, AAA said.

So there you have it. That guy in the BMW who’s been tailgating you for the last 3 miles? He may be a jerk, but there’s a good chance he’s a jerk with a prescription … or two … or three.

Exercise in a pill? Sign us up

You just got home from a long shift and you know you should go to the gym, but the bed is calling and you just answered. We know sometimes we have to make sacrifices in the name of fitness, but there just aren’t enough hours in the day. Unless our prayers have been answered. There could be a pill that has the benefits of working out without having to work out.

In a study published in Nature, investigators reported that they have identified a molecule made during exercise and used it on mice, which took in less food after being given the pill, which may open doors to understanding how exercise affects hunger.

©Rido/Fotolia.com

Gonorrhea and grandparents: A match made in prehistoric heaven

*Editorial note: LOTME takes no responsibility for any unfortunate imagery the reader may have experienced from the above headline.

Old people are the greatest. Back pains, cognitive decline, aches in all the diodes down your left side, there’s nothing quite like your golden years. Notably, however, humans are one of the few animals who experience true old age, as most creatures are adapted to maximize reproductive potential. As such, living past menopause is rare in the animal kingdom.

CDC/John Martin Jr.

This is where the “grandmother hypothesis” comes in: Back in Ye Olde Stone Age, women who lived into old age could provide child care for younger women, because human babies require a lot more time and attention than other animal offspring. But how did humans end up living so long? Enter a group of Californian researchers, who believe they have an answer. It was gonorrhea.

When compared with the chimpanzee genome (as well as with Neanderthals and Denisovans, our closest ancestors), humans have a unique mutated version of the CD33 gene that lacks a sugar-binding site; the standard version uses the sugar-binding site to protect against autoimmune response in the body, but that same site actually suppresses the brain’s ability to clear away damaged brain cells and amyloid, which eventually leads to diseases like dementia. The mutated version allows microglia (brain immune cells) to attack and clear out this unwanted material. People with higher levels of this mutated CD33 variant actually have higher protection against Alzheimer’s.

Interestingly, gonorrhea bacteria are coated in the same sugar that standard CD33 receptors bind to, thus allowing them to bypass the body’s immune system. According to the researchers, the mutated CD33 version likely emerged as a protection against gonorrhea, depriving the bacteria of their “molecular mimicry” abilities. In one of life’s happy accidents, it turned out this mutation also protects against age-related diseases, thus allowing humans with the mutation to live longer. Obviously, this was a good thing, and we ran with it until the modern day. Now we have senior citizens climbing Everest, and all our politicians keep on politicking into their 70s and 80s ... well, everything has its drawbacks.
 

Parents raise a glass to children’s food addiction

There can be something pretty addicting about processed foods. Have you ever eaten just one french fry? Or taken just one cookie? If so, your willpower is incredible. For many of us, it can be a struggle to stop.

© Aleksandr Stennikov/Fotolia.com

A recent study from the University of Michigan, which considered the existence of an eating phenotype, suggests our parents’ habits could be to blame.

By administering a series of questionnaires that inquired about food addiction, alcohol use disorders, cannabis use disorder, nicotine/e-cigarette dependence, and their family tree, investigators found that participants with a “paternal history of problematic alcohol use” had higher risk of food addiction but not obesity.

Apparently about one in five people display a clinically significant addiction to highly processed foods. It was noted that foods like ice cream, pizza, and french fries have high amounts of refined carbs and fats, which could trigger an addictive response.

Lindzey Hoover, a graduate student at the university who was the study’s lead author, noted that living in an environment where these foods are cheap and accessible can be really challenging for those with a family history of addiction. The investigators suggested that public health approaches, like restriction of other substances and marketing to kids, should be put in place for highly processed foods.

Maybe french fries should come with a warning label.
 

A prescription for America’s traffic problems

Nostalgia is a funny thing. Do you ever feel nostalgic about things that really weren’t very pleasant in the first place? Take, for instance, the morning commute. Here in the Washington area, more than 2 years into the COVID era, the traffic is still not what it used to be … and we kind of miss it.

PhotoDisk

Nah, not really. That was just a way to get everyone thinking about driving, because AAA has something of an explanation for the situation out there on the highways and byways of America. It’s drugs. No, not those kinds of drugs. This time it’s prescription drugs that are the problem. Well, part of the problem, anyway.

AAA did a survey last summer and found that nearly 50% of drivers “used one or more potentially impairing medications in the past 30 days. … The proportion of those choosing to drive is higher among those taking multiple medications.” How much higher? More than 63% of those with two or more prescriptions were driving within 2 hours of taking at least one of those meds, as were 71% of those taking three or more.

The 2,657 respondents also were asked about the types of potentially impairing drugs they were taking: 61% of those using antidepressants had been on the road within 2 hours of use at least once in the past 30 days, as had 73% of those taking an amphetamine, AAA said.

So there you have it. That guy in the BMW who’s been tailgating you for the last 3 miles? He may be a jerk, but there’s a good chance he’s a jerk with a prescription … or two … or three.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


Women who become pregnant during in vitro fertilization (IVF) from previously frozen embryos have a significantly higher chance of developing hypertensive disorders such as preeclampsia than do women who become pregnant through natural conception, researchers have found.

The new findings come from a study presented at the 2022 annual meeting of the European Society of Human Reproduction and Embryology. In the study, which will soon be published in Hypertension, researchers analyzed more than 4.5 million pregnancies from Denmark, Norway, and Sweden.

“Our findings are significant because frozen embryo transfers are increasingly common all over the world, partly due to the elective freezing of all embryos,” said Sindre Hoff Petersen, PhD, a fellow in the department of public health and nursing at the Norwegian University of Science and Technology, Trondheim, who led the study.

More than 320,000 IVF procedures were performed in the United States in 2020, according to preliminary data from the Centers for Disease Control and Prevention.

Of those, more than 123,000 eggs or embryos were frozen for future use.

The use of assisted reproductive technology, which includes IVF, has more than doubled during the past decade, the CDC reports. Roughly 2% of all babies born in the United States each year are conceived through assisted reproductive technology.

Dr. Petersen and his colleagues compared maternal complications in sibling pregnancies. Women who became pregnant following the transfer of a frozen embryo were 74% more likely to develop a hypertensive disorder than women who became pregnant following natural conception (7.4% vs. 4.3%; adjusted odds ratio, 1.74; 95% confidence interval, P < .001). The difference was even higher with respect to sibling births: Women who became pregnant using frozen embryos were 102% more likely than women who became pregnant using natural conception to develop a hypertensive disorder (adjusted odds ratio 2.02; 95% CI, 1.72-2.39, P < .001).

The researchers found no difference in the risk of hypertensive disorders between women who used fresh embryos during IVF and women who used natural conception (5.9% vs. 4.3%, 95% CI, P = .382).

“When we find that the association between frozen embryo transfer and hypertensive disorders in pregnancy persists in sibling comparisons, we believe we have strong indications that treatment factors might in fact contribute to the higher risk,” Dr. Petersen told this news organization.

Women in the study who became pregnant after natural conception had a 4.3% chance of developing hypertensive disorders. That effect persisted after controlling for maternal body mass index, smoking, and time between deliveries, he said.

The findings can add to discussions between patients and doctors on the potential benefits and harms of freezing embryos on an elective basis if there is no clinical indication, Dr. Petersen said. The frozen method is most often used to transfer a single embryo in order to reduce the incidence of multiple pregnancies, such as twins and triplets, which in turn reduces pregnancy complications.

“The vast majority of IVF pregnancies, including frozen embryo transfer, are healthy and uncomplicated, and both short- and long-term outcomes for both the mother and the children are very reassuring,” Dr. Petersen said.

Women who become pregnant through use of frozen embryos should be more closely monitored for potential hypertensive disorders, although more work is needed to determine the reasons for the association, said Elizabeth S. Ginsburg, MD, at Brigham and Women’s Hospital and professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, both in Boston.

“This is something general ob.gyns. need to be aware of, but it’s not clear which subpopulations of patients are going to be affected,” Dr. Ginsburg said. “More investigation is needed to determine if this is caused by the way the uterus is readied for the embryo transfer or if it’s patient population etiology.”

Some studies have suggested that the absence of a hormone-producing cyst, which forms on the ovary during each menstrual cycle, could explain the link between frozen embryo transfer and heightened preeclampsia risk.

Dr. Petersen and Dr. Ginsburg reported no relevant financial relationships.

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

Women who become pregnant during in vitro fertilization (IVF) from previously frozen embryos have a significantly higher chance of developing hypertensive disorders such as preeclampsia than do women who become pregnant through natural conception, researchers have found.

The new findings come from a study presented at the 2022 annual meeting of the European Society of Human Reproduction and Embryology. In the study, which will soon be published in Hypertension, researchers analyzed more than 4.5 million pregnancies from Denmark, Norway, and Sweden.

“Our findings are significant because frozen embryo transfers are increasingly common all over the world, partly due to the elective freezing of all embryos,” said Sindre Hoff Petersen, PhD, a fellow in the department of public health and nursing at the Norwegian University of Science and Technology, Trondheim, who led the study.

More than 320,000 IVF procedures were performed in the United States in 2020, according to preliminary data from the Centers for Disease Control and Prevention.

Of those, more than 123,000 eggs or embryos were frozen for future use.

The use of assisted reproductive technology, which includes IVF, has more than doubled during the past decade, the CDC reports. Roughly 2% of all babies born in the United States each year are conceived through assisted reproductive technology.

Dr. Petersen and his colleagues compared maternal complications in sibling pregnancies. Women who became pregnant following the transfer of a frozen embryo were 74% more likely to develop a hypertensive disorder than women who became pregnant following natural conception (7.4% vs. 4.3%; adjusted odds ratio, 1.74; 95% confidence interval, P < .001). The difference was even higher with respect to sibling births: Women who became pregnant using frozen embryos were 102% more likely than women who became pregnant using natural conception to develop a hypertensive disorder (adjusted odds ratio 2.02; 95% CI, 1.72-2.39, P < .001).

The researchers found no difference in the risk of hypertensive disorders between women who used fresh embryos during IVF and women who used natural conception (5.9% vs. 4.3%, 95% CI, P = .382).

“When we find that the association between frozen embryo transfer and hypertensive disorders in pregnancy persists in sibling comparisons, we believe we have strong indications that treatment factors might in fact contribute to the higher risk,” Dr. Petersen told this news organization.

Women in the study who became pregnant after natural conception had a 4.3% chance of developing hypertensive disorders. That effect persisted after controlling for maternal body mass index, smoking, and time between deliveries, he said.

The findings can add to discussions between patients and doctors on the potential benefits and harms of freezing embryos on an elective basis if there is no clinical indication, Dr. Petersen said. The frozen method is most often used to transfer a single embryo in order to reduce the incidence of multiple pregnancies, such as twins and triplets, which in turn reduces pregnancy complications.

“The vast majority of IVF pregnancies, including frozen embryo transfer, are healthy and uncomplicated, and both short- and long-term outcomes for both the mother and the children are very reassuring,” Dr. Petersen said.

Women who become pregnant through use of frozen embryos should be more closely monitored for potential hypertensive disorders, although more work is needed to determine the reasons for the association, said Elizabeth S. Ginsburg, MD, at Brigham and Women’s Hospital and professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, both in Boston.

“This is something general ob.gyns. need to be aware of, but it’s not clear which subpopulations of patients are going to be affected,” Dr. Ginsburg said. “More investigation is needed to determine if this is caused by the way the uterus is readied for the embryo transfer or if it’s patient population etiology.”

Some studies have suggested that the absence of a hormone-producing cyst, which forms on the ovary during each menstrual cycle, could explain the link between frozen embryo transfer and heightened preeclampsia risk.

Dr. Petersen and Dr. Ginsburg reported no relevant financial relationships.

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

Women who become pregnant during in vitro fertilization (IVF) from previously frozen embryos have a significantly higher chance of developing hypertensive disorders such as preeclampsia than do women who become pregnant through natural conception, researchers have found.

The new findings come from a study presented at the 2022 annual meeting of the European Society of Human Reproduction and Embryology. In the study, which will soon be published in Hypertension, researchers analyzed more than 4.5 million pregnancies from Denmark, Norway, and Sweden.

“Our findings are significant because frozen embryo transfers are increasingly common all over the world, partly due to the elective freezing of all embryos,” said Sindre Hoff Petersen, PhD, a fellow in the department of public health and nursing at the Norwegian University of Science and Technology, Trondheim, who led the study.

More than 320,000 IVF procedures were performed in the United States in 2020, according to preliminary data from the Centers for Disease Control and Prevention.

Of those, more than 123,000 eggs or embryos were frozen for future use.

The use of assisted reproductive technology, which includes IVF, has more than doubled during the past decade, the CDC reports. Roughly 2% of all babies born in the United States each year are conceived through assisted reproductive technology.

Dr. Petersen and his colleagues compared maternal complications in sibling pregnancies. Women who became pregnant following the transfer of a frozen embryo were 74% more likely to develop a hypertensive disorder than women who became pregnant following natural conception (7.4% vs. 4.3%; adjusted odds ratio, 1.74; 95% confidence interval, P < .001). The difference was even higher with respect to sibling births: Women who became pregnant using frozen embryos were 102% more likely than women who became pregnant using natural conception to develop a hypertensive disorder (adjusted odds ratio 2.02; 95% CI, 1.72-2.39, P < .001).

The researchers found no difference in the risk of hypertensive disorders between women who used fresh embryos during IVF and women who used natural conception (5.9% vs. 4.3%, 95% CI, P = .382).

“When we find that the association between frozen embryo transfer and hypertensive disorders in pregnancy persists in sibling comparisons, we believe we have strong indications that treatment factors might in fact contribute to the higher risk,” Dr. Petersen told this news organization.

Women in the study who became pregnant after natural conception had a 4.3% chance of developing hypertensive disorders. That effect persisted after controlling for maternal body mass index, smoking, and time between deliveries, he said.

The findings can add to discussions between patients and doctors on the potential benefits and harms of freezing embryos on an elective basis if there is no clinical indication, Dr. Petersen said. The frozen method is most often used to transfer a single embryo in order to reduce the incidence of multiple pregnancies, such as twins and triplets, which in turn reduces pregnancy complications.

“The vast majority of IVF pregnancies, including frozen embryo transfer, are healthy and uncomplicated, and both short- and long-term outcomes for both the mother and the children are very reassuring,” Dr. Petersen said.

Women who become pregnant through use of frozen embryos should be more closely monitored for potential hypertensive disorders, although more work is needed to determine the reasons for the association, said Elizabeth S. Ginsburg, MD, at Brigham and Women’s Hospital and professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, both in Boston.

“This is something general ob.gyns. need to be aware of, but it’s not clear which subpopulations of patients are going to be affected,” Dr. Ginsburg said. “More investigation is needed to determine if this is caused by the way the uterus is readied for the embryo transfer or if it’s patient population etiology.”

Some studies have suggested that the absence of a hormone-producing cyst, which forms on the ovary during each menstrual cycle, could explain the link between frozen embryo transfer and heightened preeclampsia risk.

Dr. Petersen and Dr. Ginsburg reported no relevant financial relationships.

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