Cardiology

The leading causes of death in the United States are cardiovascular disease (CVD) and cancer. CVD causes about 800,00 deaths per year (30% of all deaths), and cancer is responsible for about 600,000 deaths annually (21%).¹ Many adults—more than 50%—report regular use of dietary supplements, including multivitamins and minerals, to improve their overall health, believing that these supplements’ anti-inflammatory and antioxidative properties help prevent CVD and cancer.² However, this belief is not supported by evidence, according to the US Preventive Services Task Force.

What did the Task Force find? After a recent reassessment of the topic of vitamin and mineral supplementation, the Task Force reaffirmed its position from 2014: There is insufficient evidence to recommend the use of vitamins and minerals to prevent CVD and cancer.³

For most of the vitamins and minerals included in the systematic review—vitamins A, C, D, E, and K; B vitamins; calcium; iron; zinc; and selenium—the Task Force could not find sufficient evidence to make a recommendation. It is important to note that if any of these are taken at the recommended levels, there is no evidence of serious harm from using them.

However, there is good evidence to recommend against the use of beta carotene and vitamin E.³ For beta carotene, the harms outweigh the benefits: Its use is associated with an increase in the risk of CVD death, as well as an increased incidence of lung cancer in smokers and those with occupational exposure to asbestos. The evidence on vitamin E indicates that it simply does not provide any cancer or CVD mortality benefit.

How to advise patients. Both the US Department of Health and Human Services (DHHS) and the American Heart Association state that most nutritional needs can be met through the consumption of nutritional foods and beverages; supplements do not add any benefit for those who consume a healthy diet.⁴ The updated USPSTF recommendations support this approach for community-dwelling, nonpregnant adults.

For those adults who want to supplement their diets—or who need to do so because of an inability to achieve an adequate diet—urge them to follow the recommendations found in DHHS’s Dietary Guidelines for Americans, 2020-2025.⁴

The leading causes of death in the United States are cardiovascular disease (CVD) and cancer. CVD causes about 800,00 deaths per year (30% of all deaths), and cancer is responsible for about 600,000 deaths annually (21%).¹ Many adults—more than 50%—report regular use of dietary supplements, including multivitamins and minerals, to improve their overall health, believing that these supplements’ anti-inflammatory and antioxidative properties help prevent CVD and cancer.² However, this belief is not supported by evidence, according to the US Preventive Services Task Force.

What did the Task Force find? After a recent reassessment of the topic of vitamin and mineral supplementation, the Task Force reaffirmed its position from 2014: There is insufficient evidence to recommend the use of vitamins and minerals to prevent CVD and cancer.³

For most of the vitamins and minerals included in the systematic review—vitamins A, C, D, E, and K; B vitamins; calcium; iron; zinc; and selenium—the Task Force could not find sufficient evidence to make a recommendation. It is important to note that if any of these are taken at the recommended levels, there is no evidence of serious harm from using them.

However, there is good evidence to recommend against the use of beta carotene and vitamin E.³ For beta carotene, the harms outweigh the benefits: Its use is associated with an increase in the risk of CVD death, as well as an increased incidence of lung cancer in smokers and those with occupational exposure to asbestos. The evidence on vitamin E indicates that it simply does not provide any cancer or CVD mortality benefit.

How to advise patients. Both the US Department of Health and Human Services (DHHS) and the American Heart Association state that most nutritional needs can be met through the consumption of nutritional foods and beverages; supplements do not add any benefit for those who consume a healthy diet.⁴ The updated USPSTF recommendations support this approach for community-dwelling, nonpregnant adults.

For those adults who want to supplement their diets—or who need to do so because of an inability to achieve an adequate diet—urge them to follow the recommendations found in DHHS’s Dietary Guidelines for Americans, 2020-2025.⁴

The leading causes of death in the United States are cardiovascular disease (CVD) and cancer. CVD causes about 800,00 deaths per year (30% of all deaths), and cancer is responsible for about 600,000 deaths annually (21%).¹ Many adults—more than 50%—report regular use of dietary supplements, including multivitamins and minerals, to improve their overall health, believing that these supplements’ anti-inflammatory and antioxidative properties help prevent CVD and cancer.² However, this belief is not supported by evidence, according to the US Preventive Services Task Force.

What did the Task Force find? After a recent reassessment of the topic of vitamin and mineral supplementation, the Task Force reaffirmed its position from 2014: There is insufficient evidence to recommend the use of vitamins and minerals to prevent CVD and cancer.³

For most of the vitamins and minerals included in the systematic review—vitamins A, C, D, E, and K; B vitamins; calcium; iron; zinc; and selenium—the Task Force could not find sufficient evidence to make a recommendation. It is important to note that if any of these are taken at the recommended levels, there is no evidence of serious harm from using them.

However, there is good evidence to recommend against the use of beta carotene and vitamin E.³ For beta carotene, the harms outweigh the benefits: Its use is associated with an increase in the risk of CVD death, as well as an increased incidence of lung cancer in smokers and those with occupational exposure to asbestos. The evidence on vitamin E indicates that it simply does not provide any cancer or CVD mortality benefit.

How to advise patients. Both the US Department of Health and Human Services (DHHS) and the American Heart Association state that most nutritional needs can be met through the consumption of nutritional foods and beverages; supplements do not add any benefit for those who consume a healthy diet.⁴ The updated USPSTF recommendations support this approach for community-dwelling, nonpregnant adults.

For those adults who want to supplement their diets—or who need to do so because of an inability to achieve an adequate diet—urge them to follow the recommendations found in DHHS’s Dietary Guidelines for Americans, 2020-2025.⁴

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.

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.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

If 80% of individuals with hypertension were screened, 80% received treatment, and 80% then reached guideline-specified targets, up to 200 million cases of cardiovascular disease (CVD) and 130 million deaths could be averted by 2050, a modeling study suggests.

Achievement of the 80-80-80 target “could be one of the single most important global public health accomplishments of the coming decades,” according to the authors.

“We need to reprioritize hypertension care in our practices,” principal investigator David A. Watkins, MD, MPH, University of Washington, Seattle, told this news organization. “Only about one in five persons with hypertension around the world has their blood pressure well controlled. Oftentimes, clinicians are focused on addressing patients’ other health needs, many of which can be pressing in the short term, and we forget to talk about blood pressure, which has more than earned its reputation as ‘the silent killer.’ ”

The modeling study was published online  in Nature Medicine, with lead author Sarah J. Pickersgill, MPH, also from the University of Washington.
 

Two interventions, three scenarios

Dr. Watkins and colleagues based their analysis on two approaches to blood pressure (BP) control shown to be beneficial: drug treatment to a systolic BP of either 130 mm Hg or 140 mm Hg or less, depending on local guidelines, and dietary sodium reduction, as recommended by the World Health Organization.

The team modeled the impacts of these interventions in 182 countries according to three scenarios:

• Business as usual (control): allowing hypertension to increase at historic rates of change and mean sodium intake to remain at current levels
• Progress: matching historically high-performing countries (for example, accelerating hypertension control by about 3% per year at intermediate levels of intervention coverage) while lowering mean sodium intake by 15% by 2030
• Aspirational: hypertension control achieved faster than historically high-performing countries (about 4% per year) and mean sodium intake decreased by 30% by 2027

The analysis suggests that in the progressive scenario, all countries could achieve 80-80-80 targets by 2050 and most countries by 2040; the aspirational scenario would have all countries meeting them by 2040. That would result in reductions in all-cause mortality of 4%-7% (76 million to 130 million deaths averted) with progressive and aspirational interventions, respectively, compared with the control scenario.

There would also be a slower rise in expected CVD from population growth and aging (110 million to 200 million cases averted). That is, the probability of dying from any CVD cause between the ages of 30 and 80 years would be reduced by 16% in the progressive scenario and 26% in the aspirational scenario.

Of note, about 83%-85% of the potential mortality reductions would result from scaling up hypertension treatment in the progressive and aspirational scenarios, respectively, with the remaining 15%-17% coming from sodium reduction, the researchers state.

Further, they propose, scaling up BP interventions could reduce CVD inequalities across countries, with low-income and lower-middle-income countries likely experiencing the largest reductions in disease rates and mortality.
 

Implementation barriers

“Health systems in many low- and middle-income countries have not traditionally been set up to succeed in chronic disease management in primary care,” Dr. Watkins noted. For interventions to be successful, he said, “several barriers need to be addressed, including: low population awareness of chronic diseases like hypertension and diabetes, which leads to low rates of screening and treatment; high out-of-pocket cost and low availability of medicines for chronic diseases; and need for adherence support and provider incentives for improving quality of chronic disease care in primary care settings.”

“Based on the analysis, achieving the 80-80-80 seems feasible, though actually getting there may be much more complicated. I wonder whether countries have the resources to implement the needed policies,” Rodrigo M. Carrillo-Larco, MD, researcher, department of epidemiology and biostatistics, School of Public Health, Imperial College London, told this news organization.

“It may be challenging, particularly after COVID-19, which revealed deficiencies in many health care systems, and care for hypertension may have been disturbed,” said Dr. Carrillo-Larco, who is not connected with the analysis.

That said, simplified BP screening approaches could help maximize the number of people screened overall, potentially identifying those with hypertension and raising awareness, he proposed. His team’s recent study showed that such approaches vary from country to country but are generally reliable and can be used effectively for population screening.

In addition, Dr. Carrillo-Larco said, any efforts by clinicians to improve adherence and help patients achieve BP control “would also have positive effects at the population level.”

The study was supported by a grant from the Bill & Melinda Gates Foundation, with additional funding by a grant to Dr. Watkins from Resolve to Save Lives. No conflicts of interest were declared.

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

If 80% of individuals with hypertension were screened, 80% received treatment, and 80% then reached guideline-specified targets, up to 200 million cases of cardiovascular disease (CVD) and 130 million deaths could be averted by 2050, a modeling study suggests.

Achievement of the 80-80-80 target “could be one of the single most important global public health accomplishments of the coming decades,” according to the authors.

“We need to reprioritize hypertension care in our practices,” principal investigator David A. Watkins, MD, MPH, University of Washington, Seattle, told this news organization. “Only about one in five persons with hypertension around the world has their blood pressure well controlled. Oftentimes, clinicians are focused on addressing patients’ other health needs, many of which can be pressing in the short term, and we forget to talk about blood pressure, which has more than earned its reputation as ‘the silent killer.’ ”

The modeling study was published online  in Nature Medicine, with lead author Sarah J. Pickersgill, MPH, also from the University of Washington.
 

Two interventions, three scenarios

Dr. Watkins and colleagues based their analysis on two approaches to blood pressure (BP) control shown to be beneficial: drug treatment to a systolic BP of either 130 mm Hg or 140 mm Hg or less, depending on local guidelines, and dietary sodium reduction, as recommended by the World Health Organization.

The team modeled the impacts of these interventions in 182 countries according to three scenarios:

• Business as usual (control): allowing hypertension to increase at historic rates of change and mean sodium intake to remain at current levels
• Progress: matching historically high-performing countries (for example, accelerating hypertension control by about 3% per year at intermediate levels of intervention coverage) while lowering mean sodium intake by 15% by 2030
• Aspirational: hypertension control achieved faster than historically high-performing countries (about 4% per year) and mean sodium intake decreased by 30% by 2027

The analysis suggests that in the progressive scenario, all countries could achieve 80-80-80 targets by 2050 and most countries by 2040; the aspirational scenario would have all countries meeting them by 2040. That would result in reductions in all-cause mortality of 4%-7% (76 million to 130 million deaths averted) with progressive and aspirational interventions, respectively, compared with the control scenario.

There would also be a slower rise in expected CVD from population growth and aging (110 million to 200 million cases averted). That is, the probability of dying from any CVD cause between the ages of 30 and 80 years would be reduced by 16% in the progressive scenario and 26% in the aspirational scenario.

Of note, about 83%-85% of the potential mortality reductions would result from scaling up hypertension treatment in the progressive and aspirational scenarios, respectively, with the remaining 15%-17% coming from sodium reduction, the researchers state.

Further, they propose, scaling up BP interventions could reduce CVD inequalities across countries, with low-income and lower-middle-income countries likely experiencing the largest reductions in disease rates and mortality.
 

Implementation barriers

“Health systems in many low- and middle-income countries have not traditionally been set up to succeed in chronic disease management in primary care,” Dr. Watkins noted. For interventions to be successful, he said, “several barriers need to be addressed, including: low population awareness of chronic diseases like hypertension and diabetes, which leads to low rates of screening and treatment; high out-of-pocket cost and low availability of medicines for chronic diseases; and need for adherence support and provider incentives for improving quality of chronic disease care in primary care settings.”

“Based on the analysis, achieving the 80-80-80 seems feasible, though actually getting there may be much more complicated. I wonder whether countries have the resources to implement the needed policies,” Rodrigo M. Carrillo-Larco, MD, researcher, department of epidemiology and biostatistics, School of Public Health, Imperial College London, told this news organization.

“It may be challenging, particularly after COVID-19, which revealed deficiencies in many health care systems, and care for hypertension may have been disturbed,” said Dr. Carrillo-Larco, who is not connected with the analysis.

That said, simplified BP screening approaches could help maximize the number of people screened overall, potentially identifying those with hypertension and raising awareness, he proposed. His team’s recent study showed that such approaches vary from country to country but are generally reliable and can be used effectively for population screening.

In addition, Dr. Carrillo-Larco said, any efforts by clinicians to improve adherence and help patients achieve BP control “would also have positive effects at the population level.”

The study was supported by a grant from the Bill & Melinda Gates Foundation, with additional funding by a grant to Dr. Watkins from Resolve to Save Lives. No conflicts of interest were declared.

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

If 80% of individuals with hypertension were screened, 80% received treatment, and 80% then reached guideline-specified targets, up to 200 million cases of cardiovascular disease (CVD) and 130 million deaths could be averted by 2050, a modeling study suggests.

Achievement of the 80-80-80 target “could be one of the single most important global public health accomplishments of the coming decades,” according to the authors.

“We need to reprioritize hypertension care in our practices,” principal investigator David A. Watkins, MD, MPH, University of Washington, Seattle, told this news organization. “Only about one in five persons with hypertension around the world has their blood pressure well controlled. Oftentimes, clinicians are focused on addressing patients’ other health needs, many of which can be pressing in the short term, and we forget to talk about blood pressure, which has more than earned its reputation as ‘the silent killer.’ ”

The modeling study was published online  in Nature Medicine, with lead author Sarah J. Pickersgill, MPH, also from the University of Washington.
 

Two interventions, three scenarios

Dr. Watkins and colleagues based their analysis on two approaches to blood pressure (BP) control shown to be beneficial: drug treatment to a systolic BP of either 130 mm Hg or 140 mm Hg or less, depending on local guidelines, and dietary sodium reduction, as recommended by the World Health Organization.

The team modeled the impacts of these interventions in 182 countries according to three scenarios:

• Business as usual (control): allowing hypertension to increase at historic rates of change and mean sodium intake to remain at current levels
• Progress: matching historically high-performing countries (for example, accelerating hypertension control by about 3% per year at intermediate levels of intervention coverage) while lowering mean sodium intake by 15% by 2030
• Aspirational: hypertension control achieved faster than historically high-performing countries (about 4% per year) and mean sodium intake decreased by 30% by 2027

The analysis suggests that in the progressive scenario, all countries could achieve 80-80-80 targets by 2050 and most countries by 2040; the aspirational scenario would have all countries meeting them by 2040. That would result in reductions in all-cause mortality of 4%-7% (76 million to 130 million deaths averted) with progressive and aspirational interventions, respectively, compared with the control scenario.

There would also be a slower rise in expected CVD from population growth and aging (110 million to 200 million cases averted). That is, the probability of dying from any CVD cause between the ages of 30 and 80 years would be reduced by 16% in the progressive scenario and 26% in the aspirational scenario.

Of note, about 83%-85% of the potential mortality reductions would result from scaling up hypertension treatment in the progressive and aspirational scenarios, respectively, with the remaining 15%-17% coming from sodium reduction, the researchers state.

Further, they propose, scaling up BP interventions could reduce CVD inequalities across countries, with low-income and lower-middle-income countries likely experiencing the largest reductions in disease rates and mortality.
 

Implementation barriers

“Health systems in many low- and middle-income countries have not traditionally been set up to succeed in chronic disease management in primary care,” Dr. Watkins noted. For interventions to be successful, he said, “several barriers need to be addressed, including: low population awareness of chronic diseases like hypertension and diabetes, which leads to low rates of screening and treatment; high out-of-pocket cost and low availability of medicines for chronic diseases; and need for adherence support and provider incentives for improving quality of chronic disease care in primary care settings.”

“Based on the analysis, achieving the 80-80-80 seems feasible, though actually getting there may be much more complicated. I wonder whether countries have the resources to implement the needed policies,” Rodrigo M. Carrillo-Larco, MD, researcher, department of epidemiology and biostatistics, School of Public Health, Imperial College London, told this news organization.

“It may be challenging, particularly after COVID-19, which revealed deficiencies in many health care systems, and care for hypertension may have been disturbed,” said Dr. Carrillo-Larco, who is not connected with the analysis.

That said, simplified BP screening approaches could help maximize the number of people screened overall, potentially identifying those with hypertension and raising awareness, he proposed. His team’s recent study showed that such approaches vary from country to country but are generally reliable and can be used effectively for population screening.

In addition, Dr. Carrillo-Larco said, any efforts by clinicians to improve adherence and help patients achieve BP control “would also have positive effects at the population level.”

The study was supported by a grant from the Bill & Melinda Gates Foundation, with additional funding by a grant to Dr. Watkins from Resolve to Save Lives. No conflicts of interest were declared.

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

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

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

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

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

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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