CAD & Atherosclerosis

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.

The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.

The trial, first reported at last year’s American Heart Association meeting, was  published online March 16 in the Journal of the American Medical Association.

Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.

The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.

In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.

In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.

“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.

The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D₃ have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.

“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.

The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D₃ and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.

Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).

For the vitamin D₃ vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.

“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D₃ for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.

Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”

The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D₃ supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.

They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.

For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D₃, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.

“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.

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

There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.

The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.

The trial, first reported at last year’s American Heart Association meeting, was  published online March 16 in the Journal of the American Medical Association.

Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.

The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.

In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.

In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.

“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.

The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D₃ have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.

“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.

The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D₃ and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.

Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).

For the vitamin D₃ vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.

“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D₃ for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.

Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”

The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D₃ supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.

They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.

For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D₃, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.

“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.

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

There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.

The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.

The trial, first reported at last year’s American Heart Association meeting, was  published online March 16 in the Journal of the American Medical Association.

Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.

The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.

In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.

In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.

“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.

The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D₃ have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.

“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.

The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D₃ and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.

Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).

For the vitamin D₃ vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.

“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D₃ for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.

Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”

The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D₃ supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.

They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.

For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D₃, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.

“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.

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

In a placebo-controlled randomized trial, a preprocedural dose of colchicine administered immediately before percutaneous coronary intervention (PCI) for an acute ST-segment elevated myocardial infarction (STEMI) did not reduce the no-reflow phenomenon or improve outcomes.

No-reflow, in which insufficient myocardial perfusion is present even though the coronary artery appears patent, was the primary outcome, and the proportion of patients experiencing this event was exactly the same (14.4%) in the colchicine and placebo groups, reported Yaser Jenab, MD, at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

The hypothesis that colchicine would offer benefit in this setting was largely based on the Colchicine Cardiovascular Outcomes Trial (COLCOT). In that study, colchicine was associated with a 23% reduction in risk for major adverse cardiovascular events (MACE) relative to placebo when administered within 30 days after a myocardial infarction (hazard ratio, 0.77; P = .02).

The benefit in that trial was attributed to an anti-inflammatory effect, according to Dr. Jenab, associate professor of cardiology at Tehran (Iran) Heart Center. In particular as it relates to vascular disease, he cited experimental studies associating colchicine with a reduction in neutrophil activation and adherence to vascular endothelium.

The rationale for a preprocedural approach to colchicine was supplied by a subsequent time-to-treatment COLCOT analysis. In this study, MACE risk reduction for colchicine climbed to 48% (HR 0.52) for those treated within 3 days of the MI but largely disappeared (HR 0.96) if treatment was started at least 8 days post MI.
 

PodCAST-PCI trial

In the preprocedural study, called the PodCAST-PCI trial, 321 acute STEMI patients were randomized. Patients received a 1-mg dose of oral colchicine or placebo at the time PCI was scheduled. Another dose of colchicine (0.5 mg) or placebo was administered 1 hour after the procedure.

Of secondary outcomes, which included MACE at 1 month and 1 year, ST-segment resolution at 1 month, and change in inflammatory markers at 1 month, none were significant. Few even trended for significance.

For MACE, which included cardiac death, stroke, nonfatal MI, new hospitalization due to heart failure, or target vessel revascularization, the rates were lower in the colchicine group at 1 month (4.3% vs. 7.5%) and 1 year (9.3% vs. 11.2%), but neither approached significance.

For ST-segment resolution, the proportions were generally comparable among the colchicine and placebo groups, respectively, for the proportion below 50% (18.6% vs. 23.1%), between 50% and 70% (16.8% vs. 15.6%), and above 70% (64.6% vs. 61.3%).

The average troponin levels were nonsignificantly lower at 6 hours (1,847 vs. 2,883 ng/mL) in the colchicine group but higher at 48 hours (1,197 vs. 1,147 ng/mL). The average C-reactive protein (CRP) levels at 48 hours were nonsignificantly lower on colchicine (176.5 vs. 244.5 mg/L).

There were no significant differences in postprocedural perfusion, as measured with TIMI blood flow, or in the rate of stent thrombosis, which occurred in roughly 3% of each group of patients.

The small sample size was one limitation of this study, Dr. Jenab acknowledged. For this and other reasons, he cautioned that these data are not definitive and do not preclude a benefit on clinical outcomes in a study with a larger size, a different design, or different dosing.
 

Timing might be the issue

However, even if colchicine has a potential benefit in this setting, timing might be a major obstacle, according to Binata Shah, MD, associate director of research for the Cardiac Catheterization Laboratory at New York University.

“We have learned from our rheumatology colleagues that peak plasma levels of colchicine are not achieved for at least 1 hour after the full loading dose,” Dr. Shah said. “With us moving so quickly in a primary PCI setting, it is hard to imagine that colchicine would have had time to really kick in and exert its anti-inflammatory effect.”

Indeed, the problem might be worse than reaching the peak plasma level.

“Even though peak plasma levels occur as early as 1 hour after a full loading dose, we see that it takes about 24 hours to really see the effects translate downstream into more systemic inflammatory markers such as CRP and interleukin-6,” she added. If lowering these signals of inflammation is predictive of benefit, than this might be the biggest obstacle to benefit from colchicine in an urgent treatment setting.

Dr. Jenab and Dr. Shah reported no potential conflicts of interest.

In a placebo-controlled randomized trial, a preprocedural dose of colchicine administered immediately before percutaneous coronary intervention (PCI) for an acute ST-segment elevated myocardial infarction (STEMI) did not reduce the no-reflow phenomenon or improve outcomes.

No-reflow, in which insufficient myocardial perfusion is present even though the coronary artery appears patent, was the primary outcome, and the proportion of patients experiencing this event was exactly the same (14.4%) in the colchicine and placebo groups, reported Yaser Jenab, MD, at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

The hypothesis that colchicine would offer benefit in this setting was largely based on the Colchicine Cardiovascular Outcomes Trial (COLCOT). In that study, colchicine was associated with a 23% reduction in risk for major adverse cardiovascular events (MACE) relative to placebo when administered within 30 days after a myocardial infarction (hazard ratio, 0.77; P = .02).

The benefit in that trial was attributed to an anti-inflammatory effect, according to Dr. Jenab, associate professor of cardiology at Tehran (Iran) Heart Center. In particular as it relates to vascular disease, he cited experimental studies associating colchicine with a reduction in neutrophil activation and adherence to vascular endothelium.

The rationale for a preprocedural approach to colchicine was supplied by a subsequent time-to-treatment COLCOT analysis. In this study, MACE risk reduction for colchicine climbed to 48% (HR 0.52) for those treated within 3 days of the MI but largely disappeared (HR 0.96) if treatment was started at least 8 days post MI.
 

PodCAST-PCI trial

In the preprocedural study, called the PodCAST-PCI trial, 321 acute STEMI patients were randomized. Patients received a 1-mg dose of oral colchicine or placebo at the time PCI was scheduled. Another dose of colchicine (0.5 mg) or placebo was administered 1 hour after the procedure.

Of secondary outcomes, which included MACE at 1 month and 1 year, ST-segment resolution at 1 month, and change in inflammatory markers at 1 month, none were significant. Few even trended for significance.

For MACE, which included cardiac death, stroke, nonfatal MI, new hospitalization due to heart failure, or target vessel revascularization, the rates were lower in the colchicine group at 1 month (4.3% vs. 7.5%) and 1 year (9.3% vs. 11.2%), but neither approached significance.

For ST-segment resolution, the proportions were generally comparable among the colchicine and placebo groups, respectively, for the proportion below 50% (18.6% vs. 23.1%), between 50% and 70% (16.8% vs. 15.6%), and above 70% (64.6% vs. 61.3%).

The average troponin levels were nonsignificantly lower at 6 hours (1,847 vs. 2,883 ng/mL) in the colchicine group but higher at 48 hours (1,197 vs. 1,147 ng/mL). The average C-reactive protein (CRP) levels at 48 hours were nonsignificantly lower on colchicine (176.5 vs. 244.5 mg/L).

There were no significant differences in postprocedural perfusion, as measured with TIMI blood flow, or in the rate of stent thrombosis, which occurred in roughly 3% of each group of patients.

The small sample size was one limitation of this study, Dr. Jenab acknowledged. For this and other reasons, he cautioned that these data are not definitive and do not preclude a benefit on clinical outcomes in a study with a larger size, a different design, or different dosing.
 

Timing might be the issue

However, even if colchicine has a potential benefit in this setting, timing might be a major obstacle, according to Binata Shah, MD, associate director of research for the Cardiac Catheterization Laboratory at New York University.

“We have learned from our rheumatology colleagues that peak plasma levels of colchicine are not achieved for at least 1 hour after the full loading dose,” Dr. Shah said. “With us moving so quickly in a primary PCI setting, it is hard to imagine that colchicine would have had time to really kick in and exert its anti-inflammatory effect.”

Indeed, the problem might be worse than reaching the peak plasma level.

“Even though peak plasma levels occur as early as 1 hour after a full loading dose, we see that it takes about 24 hours to really see the effects translate downstream into more systemic inflammatory markers such as CRP and interleukin-6,” she added. If lowering these signals of inflammation is predictive of benefit, than this might be the biggest obstacle to benefit from colchicine in an urgent treatment setting.

Dr. Jenab and Dr. Shah reported no potential conflicts of interest.

In a placebo-controlled randomized trial, a preprocedural dose of colchicine administered immediately before percutaneous coronary intervention (PCI) for an acute ST-segment elevated myocardial infarction (STEMI) did not reduce the no-reflow phenomenon or improve outcomes.

No-reflow, in which insufficient myocardial perfusion is present even though the coronary artery appears patent, was the primary outcome, and the proportion of patients experiencing this event was exactly the same (14.4%) in the colchicine and placebo groups, reported Yaser Jenab, MD, at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

The hypothesis that colchicine would offer benefit in this setting was largely based on the Colchicine Cardiovascular Outcomes Trial (COLCOT). In that study, colchicine was associated with a 23% reduction in risk for major adverse cardiovascular events (MACE) relative to placebo when administered within 30 days after a myocardial infarction (hazard ratio, 0.77; P = .02).

The benefit in that trial was attributed to an anti-inflammatory effect, according to Dr. Jenab, associate professor of cardiology at Tehran (Iran) Heart Center. In particular as it relates to vascular disease, he cited experimental studies associating colchicine with a reduction in neutrophil activation and adherence to vascular endothelium.

The rationale for a preprocedural approach to colchicine was supplied by a subsequent time-to-treatment COLCOT analysis. In this study, MACE risk reduction for colchicine climbed to 48% (HR 0.52) for those treated within 3 days of the MI but largely disappeared (HR 0.96) if treatment was started at least 8 days post MI.
 

PodCAST-PCI trial

In the preprocedural study, called the PodCAST-PCI trial, 321 acute STEMI patients were randomized. Patients received a 1-mg dose of oral colchicine or placebo at the time PCI was scheduled. Another dose of colchicine (0.5 mg) or placebo was administered 1 hour after the procedure.

Of secondary outcomes, which included MACE at 1 month and 1 year, ST-segment resolution at 1 month, and change in inflammatory markers at 1 month, none were significant. Few even trended for significance.

For MACE, which included cardiac death, stroke, nonfatal MI, new hospitalization due to heart failure, or target vessel revascularization, the rates were lower in the colchicine group at 1 month (4.3% vs. 7.5%) and 1 year (9.3% vs. 11.2%), but neither approached significance.

For ST-segment resolution, the proportions were generally comparable among the colchicine and placebo groups, respectively, for the proportion below 50% (18.6% vs. 23.1%), between 50% and 70% (16.8% vs. 15.6%), and above 70% (64.6% vs. 61.3%).

The average troponin levels were nonsignificantly lower at 6 hours (1,847 vs. 2,883 ng/mL) in the colchicine group but higher at 48 hours (1,197 vs. 1,147 ng/mL). The average C-reactive protein (CRP) levels at 48 hours were nonsignificantly lower on colchicine (176.5 vs. 244.5 mg/L).

There were no significant differences in postprocedural perfusion, as measured with TIMI blood flow, or in the rate of stent thrombosis, which occurred in roughly 3% of each group of patients.

The small sample size was one limitation of this study, Dr. Jenab acknowledged. For this and other reasons, he cautioned that these data are not definitive and do not preclude a benefit on clinical outcomes in a study with a larger size, a different design, or different dosing.
 

Timing might be the issue

However, even if colchicine has a potential benefit in this setting, timing might be a major obstacle, according to Binata Shah, MD, associate director of research for the Cardiac Catheterization Laboratory at New York University.

“We have learned from our rheumatology colleagues that peak plasma levels of colchicine are not achieved for at least 1 hour after the full loading dose,” Dr. Shah said. “With us moving so quickly in a primary PCI setting, it is hard to imagine that colchicine would have had time to really kick in and exert its anti-inflammatory effect.”

Indeed, the problem might be worse than reaching the peak plasma level.

“Even though peak plasma levels occur as early as 1 hour after a full loading dose, we see that it takes about 24 hours to really see the effects translate downstream into more systemic inflammatory markers such as CRP and interleukin-6,” she added. If lowering these signals of inflammation is predictive of benefit, than this might be the biggest obstacle to benefit from colchicine in an urgent treatment setting.

Dr. Jenab and Dr. Shah reported no potential conflicts of interest.

For a primary composite target-lesion failure outcome, a biodegradable polymer sirolimus-eluting stent showed superiority at 2 years over a durable polymer everolimus-eluting stent in patients undergoing percutaneous intervention (PCI) for an ST-segment elevated acute myocardial infarction (STEMI), according to a late-breaking trial presentation at CRT 2021.

As in the previously reported 1-year results from the BIOSTEMI trial, the advantage of the biodegradable device was “driven by lower rates of target-lesion revascularization,” reported Thomas Pilgrim, MD, of the University of Bern (Switzerland).

Drug-eluting stents have already been established as superior to bare-metal stents, but the question asked in this study is whether the polymer that carries antiproliferative drugs, such as sirolimus or everolimus, improves lesion-based outcomes if it is biodegradable rather than durable, Dr. Pilgrim explained.

The composite primary outcome was target-lesion failure defined by cardiac death, target-lesion MI, or clinically indicated target-lesion revascularization.

After 2 years of follow-up, the rates of target-lesion failure were 5.1% and 8.1% for the biodegradable and durable polymer stents, respectively. This 0.58 rate ratio was statistically significant, favoring the biodegradable stent.

The investigator-initiated BIOSTEMI trial randomized 1,300 patients to one of two drug-eluting stents with ultrathin struts. One was the Orsiro stent that employs a biodegradable polymer to deliver sirolimus. The other was the Xience Prime/Xpedition that uses a durable polymer stent to deliver everolimus.

The strut thicknesses of the Orsiro stent are 60 mcm for stents of 3.0 mm in diameter or smaller and 80 mcm for those with a larger diameter. The strut thickness of the Xience stent is 81 mcm regardless of diameter.

“Patients with an acute myocardial infarction are at increased risk of stent-related events due to exacerbated inflammatory response and delayed arterial healing,” Dr. Pilgrim said. The theoretical advantages of polymer that biodegrades include “mitigation of the arterial injury, facilitation of endothelialization, and reduced intimal hyperplasia,” he explained at the meeting sponsored by MedStar Heart & Vascular Institute.

The rates of cardiac death (2.9% vs. 3.2%) and target-vessel MI (2.9% vs. 3.2%) were lower for the biodegradable polymer stent, but not significantly. However, the rates of target-vessel revascularization at 2 years were 2.5% versus 5.1%. The associated rate ratio of 0.52 favoring the biodegradable stent was significant.

Similar results favoring the biodegradable polymer stent were observed at 1 year, but those earlier results factored in historical data from the BIOSCIENCE trial, using a Bayesian analysis, to improve the power of the comparison. In this 2-year analysis, the superiority of the biodegradable polymer stent to the durable polymer stent remained statistically significant even when excluding those historical controls.

The advantage of the biodegradable polymer stent was confined to “device-oriented” outcomes, according to Dr. Pilgrim. When compared for important patient-oriented outcomes at 2 years, there were no significant differences. Rather, several were numerically more common, including death (4.2% vs. 3.8%) and MI (3.7% vs. 3.1%) in those who were randomized to the biodegradable polymer stent.

But these types of clinical outcomes are not necessarily related to stent assignment because “up to one-half of all events over the 2 years of follow-up were unrelated to the stent implanted,” Dr. Pilgrim said. He noted that high rates of events unrelated to the implanted stent have also been seen in follow-up of other comparative stent trials.

The superiority of the biodegradable stent is noteworthy. Although Dr. Pilgrim described the BIOSTEMI trial as “the first head-to-head comparison of two new-generation drug-eluting stents in patients undergoing a primary percutaneous intervention for acute myocardial infarction,” there have been several studies comparing stents for other indications. Significant differences have been uncommon.

“Over the last 10 years, we have seen a number of noninferiority stent trials, but only now are we seeing some superiority differences. This is a move in the right direction,” commented Sripal Bangalore, MD, director of the cardiovascular outcomes group, New York University.

However, he, like others, questioned whether the difference in outcomes in this trial could be fully attributed to the type of polymer. He noted that all stents could be characterized by multiple small and large differences in design and composition. Any specific characteristic, such as biodegradable polymer, might be an important contributor but not an isolated factor in the outcomes observed.

On the day that the 2-year results of the BIOSTEMI trial were presented at the CRT 2021 meeting they were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Pilgrim reports financial relationships with several companies that make stent devices, including Biotronik and Boston Scientific. Dr. Bangalore reports no potential conflicts of interest.

For a primary composite target-lesion failure outcome, a biodegradable polymer sirolimus-eluting stent showed superiority at 2 years over a durable polymer everolimus-eluting stent in patients undergoing percutaneous intervention (PCI) for an ST-segment elevated acute myocardial infarction (STEMI), according to a late-breaking trial presentation at CRT 2021.

As in the previously reported 1-year results from the BIOSTEMI trial, the advantage of the biodegradable device was “driven by lower rates of target-lesion revascularization,” reported Thomas Pilgrim, MD, of the University of Bern (Switzerland).

Drug-eluting stents have already been established as superior to bare-metal stents, but the question asked in this study is whether the polymer that carries antiproliferative drugs, such as sirolimus or everolimus, improves lesion-based outcomes if it is biodegradable rather than durable, Dr. Pilgrim explained.

The composite primary outcome was target-lesion failure defined by cardiac death, target-lesion MI, or clinically indicated target-lesion revascularization.

After 2 years of follow-up, the rates of target-lesion failure were 5.1% and 8.1% for the biodegradable and durable polymer stents, respectively. This 0.58 rate ratio was statistically significant, favoring the biodegradable stent.

The investigator-initiated BIOSTEMI trial randomized 1,300 patients to one of two drug-eluting stents with ultrathin struts. One was the Orsiro stent that employs a biodegradable polymer to deliver sirolimus. The other was the Xience Prime/Xpedition that uses a durable polymer stent to deliver everolimus.

The strut thicknesses of the Orsiro stent are 60 mcm for stents of 3.0 mm in diameter or smaller and 80 mcm for those with a larger diameter. The strut thickness of the Xience stent is 81 mcm regardless of diameter.

“Patients with an acute myocardial infarction are at increased risk of stent-related events due to exacerbated inflammatory response and delayed arterial healing,” Dr. Pilgrim said. The theoretical advantages of polymer that biodegrades include “mitigation of the arterial injury, facilitation of endothelialization, and reduced intimal hyperplasia,” he explained at the meeting sponsored by MedStar Heart & Vascular Institute.

The rates of cardiac death (2.9% vs. 3.2%) and target-vessel MI (2.9% vs. 3.2%) were lower for the biodegradable polymer stent, but not significantly. However, the rates of target-vessel revascularization at 2 years were 2.5% versus 5.1%. The associated rate ratio of 0.52 favoring the biodegradable stent was significant.

Similar results favoring the biodegradable polymer stent were observed at 1 year, but those earlier results factored in historical data from the BIOSCIENCE trial, using a Bayesian analysis, to improve the power of the comparison. In this 2-year analysis, the superiority of the biodegradable polymer stent to the durable polymer stent remained statistically significant even when excluding those historical controls.

The advantage of the biodegradable polymer stent was confined to “device-oriented” outcomes, according to Dr. Pilgrim. When compared for important patient-oriented outcomes at 2 years, there were no significant differences. Rather, several were numerically more common, including death (4.2% vs. 3.8%) and MI (3.7% vs. 3.1%) in those who were randomized to the biodegradable polymer stent.

But these types of clinical outcomes are not necessarily related to stent assignment because “up to one-half of all events over the 2 years of follow-up were unrelated to the stent implanted,” Dr. Pilgrim said. He noted that high rates of events unrelated to the implanted stent have also been seen in follow-up of other comparative stent trials.

The superiority of the biodegradable stent is noteworthy. Although Dr. Pilgrim described the BIOSTEMI trial as “the first head-to-head comparison of two new-generation drug-eluting stents in patients undergoing a primary percutaneous intervention for acute myocardial infarction,” there have been several studies comparing stents for other indications. Significant differences have been uncommon.

“Over the last 10 years, we have seen a number of noninferiority stent trials, but only now are we seeing some superiority differences. This is a move in the right direction,” commented Sripal Bangalore, MD, director of the cardiovascular outcomes group, New York University.

However, he, like others, questioned whether the difference in outcomes in this trial could be fully attributed to the type of polymer. He noted that all stents could be characterized by multiple small and large differences in design and composition. Any specific characteristic, such as biodegradable polymer, might be an important contributor but not an isolated factor in the outcomes observed.

On the day that the 2-year results of the BIOSTEMI trial were presented at the CRT 2021 meeting they were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Pilgrim reports financial relationships with several companies that make stent devices, including Biotronik and Boston Scientific. Dr. Bangalore reports no potential conflicts of interest.

For a primary composite target-lesion failure outcome, a biodegradable polymer sirolimus-eluting stent showed superiority at 2 years over a durable polymer everolimus-eluting stent in patients undergoing percutaneous intervention (PCI) for an ST-segment elevated acute myocardial infarction (STEMI), according to a late-breaking trial presentation at CRT 2021.

As in the previously reported 1-year results from the BIOSTEMI trial, the advantage of the biodegradable device was “driven by lower rates of target-lesion revascularization,” reported Thomas Pilgrim, MD, of the University of Bern (Switzerland).

Drug-eluting stents have already been established as superior to bare-metal stents, but the question asked in this study is whether the polymer that carries antiproliferative drugs, such as sirolimus or everolimus, improves lesion-based outcomes if it is biodegradable rather than durable, Dr. Pilgrim explained.

The composite primary outcome was target-lesion failure defined by cardiac death, target-lesion MI, or clinically indicated target-lesion revascularization.

After 2 years of follow-up, the rates of target-lesion failure were 5.1% and 8.1% for the biodegradable and durable polymer stents, respectively. This 0.58 rate ratio was statistically significant, favoring the biodegradable stent.

The investigator-initiated BIOSTEMI trial randomized 1,300 patients to one of two drug-eluting stents with ultrathin struts. One was the Orsiro stent that employs a biodegradable polymer to deliver sirolimus. The other was the Xience Prime/Xpedition that uses a durable polymer stent to deliver everolimus.

The strut thicknesses of the Orsiro stent are 60 mcm for stents of 3.0 mm in diameter or smaller and 80 mcm for those with a larger diameter. The strut thickness of the Xience stent is 81 mcm regardless of diameter.

“Patients with an acute myocardial infarction are at increased risk of stent-related events due to exacerbated inflammatory response and delayed arterial healing,” Dr. Pilgrim said. The theoretical advantages of polymer that biodegrades include “mitigation of the arterial injury, facilitation of endothelialization, and reduced intimal hyperplasia,” he explained at the meeting sponsored by MedStar Heart & Vascular Institute.

The rates of cardiac death (2.9% vs. 3.2%) and target-vessel MI (2.9% vs. 3.2%) were lower for the biodegradable polymer stent, but not significantly. However, the rates of target-vessel revascularization at 2 years were 2.5% versus 5.1%. The associated rate ratio of 0.52 favoring the biodegradable stent was significant.

Similar results favoring the biodegradable polymer stent were observed at 1 year, but those earlier results factored in historical data from the BIOSCIENCE trial, using a Bayesian analysis, to improve the power of the comparison. In this 2-year analysis, the superiority of the biodegradable polymer stent to the durable polymer stent remained statistically significant even when excluding those historical controls.

The advantage of the biodegradable polymer stent was confined to “device-oriented” outcomes, according to Dr. Pilgrim. When compared for important patient-oriented outcomes at 2 years, there were no significant differences. Rather, several were numerically more common, including death (4.2% vs. 3.8%) and MI (3.7% vs. 3.1%) in those who were randomized to the biodegradable polymer stent.

But these types of clinical outcomes are not necessarily related to stent assignment because “up to one-half of all events over the 2 years of follow-up were unrelated to the stent implanted,” Dr. Pilgrim said. He noted that high rates of events unrelated to the implanted stent have also been seen in follow-up of other comparative stent trials.

The superiority of the biodegradable stent is noteworthy. Although Dr. Pilgrim described the BIOSTEMI trial as “the first head-to-head comparison of two new-generation drug-eluting stents in patients undergoing a primary percutaneous intervention for acute myocardial infarction,” there have been several studies comparing stents for other indications. Significant differences have been uncommon.

“Over the last 10 years, we have seen a number of noninferiority stent trials, but only now are we seeing some superiority differences. This is a move in the right direction,” commented Sripal Bangalore, MD, director of the cardiovascular outcomes group, New York University.

However, he, like others, questioned whether the difference in outcomes in this trial could be fully attributed to the type of polymer. He noted that all stents could be characterized by multiple small and large differences in design and composition. Any specific characteristic, such as biodegradable polymer, might be an important contributor but not an isolated factor in the outcomes observed.

On the day that the 2-year results of the BIOSTEMI trial were presented at the CRT 2021 meeting they were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Pilgrim reports financial relationships with several companies that make stent devices, including Biotronik and Boston Scientific. Dr. Bangalore reports no potential conflicts of interest.

People with cardiovascular disease who regularly ate fish had significantly fewer major CVD events and there were fewer total deaths, compared with similar individuals who didn’t eat fish, but there was no beneficial link from eating fish among the general population in prospective data collected from more than 191,000 people from 58 countries.

Despite the neutral finding among people without CVD, the finding that eating fish was associated with significant benefit for those with CVD or who were at high risk for CVD confirms the public health importance of regular fish or fish oil consumption, said one expert.

A little over a quarter of those included in the new study had a history of CVD or were at high risk for CVD. In this subgroup of more than 51,000 people, those who consumed on average at least two servings of fish weekly (at least 175 g, or about 6.2 ounces per week) had a significant 16% lower rate of major CVD events during a median follow-up of about 7.5 years.

The rate of all-cause death was a significant 18% lower among people who ate two or more fish portions weekly, compared with those who didn’t, Deepa Mohan, PhD, and associates wrote in their report in JAMA Internal Medicine.

The researchers saw no additional benefit when people regularly ate greater amounts of fish.

“There is a significant protective benefit of fish consumption in people with cardiovascular disease,” said Andrew Mente, PhD, a senior investigator on the study and an epidemiologist at McMaster University, Hamilton, Ont..

“This study has important implications for guidelines on fish intake globally. It indicates that increasing fish consumption and particularly oily fish in vascular patients may produce a modest cardiovascular benefit,” he said in a statement released by McMaster.
 

‘A large body of evidence’ for CVD benefit

The neutral finding of no significant benefit (as well as no harm) regarding either CVD events or total mortality among people without CVD “does not alter the large body of prior observational evidence supporting the cardiac benefits of fish intake in general populations,” noted Dariush Mozaffarian, MD, DrPH, in a commentary that accompanies the report by Dr. Mohan and colleagues.

Although the new analysis failed to show a significant association between regular fish consumption and fewer CVD events for people without established CVD or CVD risk, “based on the cumulative evidence from prospective observational studies, randomized clinical trials, and mechanistic and experimental studies, modest fish consumption appears to have some cardiac benefits,” he added.

“Adults should aim to consume about two servings of fish per week, and larger benefits may accrue from nonfried oily (dark meat) fish,” wrote Dr. Mozaffarian, a professor of medicine and nutrition at Tufts University, Boston.

Oily, dark fishes include salmon, tuna steak, mackerel, herring, and sardines. Species such as these contain the highest levels of long-chain omega-3 fatty acids, eicosapentaenoic acid, and docosapentaenoic acid; these nutrients likely underlie the CVD benefits from fish, Dr. Mozaffarian said in an interview with JAMA Internal Medicine that accompanied his commentary. (Dr. Mente also participated.)

“Fish oil lowers heart rate, blood pressure, and triglycerides (at high dosages), increases adiponectin, improves endothelial function, and in some studies improves oxygen consumption in myocardium. If there is benefit from fish it’s from the omega 3s, and all in all the evidence supports this,” but because the evidence is primarily observational, it can only show linkage and cannot prove causation, he explained.

Given the potential benefit and limited risk, “I think everyone should aim to eat two servings of fish each week, preferentially oily fish. That’s very solid,” said Dr. Mozaffarian, who is also a cardiologist and dean of the Tufts Friedman School of Nutrition Science.

The investigators did not have adequate data to compare the associations between outcomes and a diet with oily fish versus less oily fish.
 

OTC fish oil capsules are ‘very reasonable’

For people who either can’t consume two fish meals a week or want to ensure their omega 3 intake is adequate, “it’s very reasonable for the average person to take one OTC [over-the-counter] fish oil capsule a day,” Dr. Mozaffarian added.

He acknowledged that several studies of fish oil supplements failed to show benefit, but several others have. “It’s a confusing field, but the evidence supports benefit from omega 3s,” he concluded.

He discounted the new finding that only people with established CVD or who are at high-risk benefit. “I’m not sure we should make too much of this, because many prior studies showed a lower CVD risk in fish-eating people without prevalent CVD,” he said. The new study “provides important information given its worldwide breadth.”

The new report used data regarding 191,558 people enrolled prospectively in any of four studies. The average age of the participants was 54 years, and 52% were women.

During follow-up, death from any cause occurred in 6% of those without CVD or CVD risk and in 13% of those with these factors. Major CVD events occurred in 5% and 17% of these two subgroups, respectively. To calculate the relative risks between those who ate fish and those who did not, the investigators used standard multivariate adjustment for potential confounders and adjusted for several dietary variables, Dr. Mente said.

Dr. Mohan and Dr. Mente disclosed no relevant financial relationships. Dr. Mozaffarian has received personal fees from Acasti Pharma, Amarin, America’s Test Kitchen, Barilla, Danone, GEOD, and Motif Food Works, and he has been an adviser to numerous companies.

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

People with cardiovascular disease who regularly ate fish had significantly fewer major CVD events and there were fewer total deaths, compared with similar individuals who didn’t eat fish, but there was no beneficial link from eating fish among the general population in prospective data collected from more than 191,000 people from 58 countries.

Despite the neutral finding among people without CVD, the finding that eating fish was associated with significant benefit for those with CVD or who were at high risk for CVD confirms the public health importance of regular fish or fish oil consumption, said one expert.

A little over a quarter of those included in the new study had a history of CVD or were at high risk for CVD. In this subgroup of more than 51,000 people, those who consumed on average at least two servings of fish weekly (at least 175 g, or about 6.2 ounces per week) had a significant 16% lower rate of major CVD events during a median follow-up of about 7.5 years.

The rate of all-cause death was a significant 18% lower among people who ate two or more fish portions weekly, compared with those who didn’t, Deepa Mohan, PhD, and associates wrote in their report in JAMA Internal Medicine.

The researchers saw no additional benefit when people regularly ate greater amounts of fish.

“There is a significant protective benefit of fish consumption in people with cardiovascular disease,” said Andrew Mente, PhD, a senior investigator on the study and an epidemiologist at McMaster University, Hamilton, Ont..

“This study has important implications for guidelines on fish intake globally. It indicates that increasing fish consumption and particularly oily fish in vascular patients may produce a modest cardiovascular benefit,” he said in a statement released by McMaster.
 

‘A large body of evidence’ for CVD benefit

The neutral finding of no significant benefit (as well as no harm) regarding either CVD events or total mortality among people without CVD “does not alter the large body of prior observational evidence supporting the cardiac benefits of fish intake in general populations,” noted Dariush Mozaffarian, MD, DrPH, in a commentary that accompanies the report by Dr. Mohan and colleagues.

Although the new analysis failed to show a significant association between regular fish consumption and fewer CVD events for people without established CVD or CVD risk, “based on the cumulative evidence from prospective observational studies, randomized clinical trials, and mechanistic and experimental studies, modest fish consumption appears to have some cardiac benefits,” he added.

“Adults should aim to consume about two servings of fish per week, and larger benefits may accrue from nonfried oily (dark meat) fish,” wrote Dr. Mozaffarian, a professor of medicine and nutrition at Tufts University, Boston.

Oily, dark fishes include salmon, tuna steak, mackerel, herring, and sardines. Species such as these contain the highest levels of long-chain omega-3 fatty acids, eicosapentaenoic acid, and docosapentaenoic acid; these nutrients likely underlie the CVD benefits from fish, Dr. Mozaffarian said in an interview with JAMA Internal Medicine that accompanied his commentary. (Dr. Mente also participated.)

“Fish oil lowers heart rate, blood pressure, and triglycerides (at high dosages), increases adiponectin, improves endothelial function, and in some studies improves oxygen consumption in myocardium. If there is benefit from fish it’s from the omega 3s, and all in all the evidence supports this,” but because the evidence is primarily observational, it can only show linkage and cannot prove causation, he explained.

Given the potential benefit and limited risk, “I think everyone should aim to eat two servings of fish each week, preferentially oily fish. That’s very solid,” said Dr. Mozaffarian, who is also a cardiologist and dean of the Tufts Friedman School of Nutrition Science.

The investigators did not have adequate data to compare the associations between outcomes and a diet with oily fish versus less oily fish.
 

OTC fish oil capsules are ‘very reasonable’

For people who either can’t consume two fish meals a week or want to ensure their omega 3 intake is adequate, “it’s very reasonable for the average person to take one OTC [over-the-counter] fish oil capsule a day,” Dr. Mozaffarian added.

He acknowledged that several studies of fish oil supplements failed to show benefit, but several others have. “It’s a confusing field, but the evidence supports benefit from omega 3s,” he concluded.

He discounted the new finding that only people with established CVD or who are at high-risk benefit. “I’m not sure we should make too much of this, because many prior studies showed a lower CVD risk in fish-eating people without prevalent CVD,” he said. The new study “provides important information given its worldwide breadth.”

The new report used data regarding 191,558 people enrolled prospectively in any of four studies. The average age of the participants was 54 years, and 52% were women.

During follow-up, death from any cause occurred in 6% of those without CVD or CVD risk and in 13% of those with these factors. Major CVD events occurred in 5% and 17% of these two subgroups, respectively. To calculate the relative risks between those who ate fish and those who did not, the investigators used standard multivariate adjustment for potential confounders and adjusted for several dietary variables, Dr. Mente said.

Dr. Mohan and Dr. Mente disclosed no relevant financial relationships. Dr. Mozaffarian has received personal fees from Acasti Pharma, Amarin, America’s Test Kitchen, Barilla, Danone, GEOD, and Motif Food Works, and he has been an adviser to numerous companies.

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

People with cardiovascular disease who regularly ate fish had significantly fewer major CVD events and there were fewer total deaths, compared with similar individuals who didn’t eat fish, but there was no beneficial link from eating fish among the general population in prospective data collected from more than 191,000 people from 58 countries.

Despite the neutral finding among people without CVD, the finding that eating fish was associated with significant benefit for those with CVD or who were at high risk for CVD confirms the public health importance of regular fish or fish oil consumption, said one expert.

A little over a quarter of those included in the new study had a history of CVD or were at high risk for CVD. In this subgroup of more than 51,000 people, those who consumed on average at least two servings of fish weekly (at least 175 g, or about 6.2 ounces per week) had a significant 16% lower rate of major CVD events during a median follow-up of about 7.5 years.

The rate of all-cause death was a significant 18% lower among people who ate two or more fish portions weekly, compared with those who didn’t, Deepa Mohan, PhD, and associates wrote in their report in JAMA Internal Medicine.

The researchers saw no additional benefit when people regularly ate greater amounts of fish.

“There is a significant protective benefit of fish consumption in people with cardiovascular disease,” said Andrew Mente, PhD, a senior investigator on the study and an epidemiologist at McMaster University, Hamilton, Ont..

“This study has important implications for guidelines on fish intake globally. It indicates that increasing fish consumption and particularly oily fish in vascular patients may produce a modest cardiovascular benefit,” he said in a statement released by McMaster.
 

‘A large body of evidence’ for CVD benefit

The neutral finding of no significant benefit (as well as no harm) regarding either CVD events or total mortality among people without CVD “does not alter the large body of prior observational evidence supporting the cardiac benefits of fish intake in general populations,” noted Dariush Mozaffarian, MD, DrPH, in a commentary that accompanies the report by Dr. Mohan and colleagues.

Although the new analysis failed to show a significant association between regular fish consumption and fewer CVD events for people without established CVD or CVD risk, “based on the cumulative evidence from prospective observational studies, randomized clinical trials, and mechanistic and experimental studies, modest fish consumption appears to have some cardiac benefits,” he added.

“Adults should aim to consume about two servings of fish per week, and larger benefits may accrue from nonfried oily (dark meat) fish,” wrote Dr. Mozaffarian, a professor of medicine and nutrition at Tufts University, Boston.

Oily, dark fishes include salmon, tuna steak, mackerel, herring, and sardines. Species such as these contain the highest levels of long-chain omega-3 fatty acids, eicosapentaenoic acid, and docosapentaenoic acid; these nutrients likely underlie the CVD benefits from fish, Dr. Mozaffarian said in an interview with JAMA Internal Medicine that accompanied his commentary. (Dr. Mente also participated.)

“Fish oil lowers heart rate, blood pressure, and triglycerides (at high dosages), increases adiponectin, improves endothelial function, and in some studies improves oxygen consumption in myocardium. If there is benefit from fish it’s from the omega 3s, and all in all the evidence supports this,” but because the evidence is primarily observational, it can only show linkage and cannot prove causation, he explained.

Given the potential benefit and limited risk, “I think everyone should aim to eat two servings of fish each week, preferentially oily fish. That’s very solid,” said Dr. Mozaffarian, who is also a cardiologist and dean of the Tufts Friedman School of Nutrition Science.

The investigators did not have adequate data to compare the associations between outcomes and a diet with oily fish versus less oily fish.
 

OTC fish oil capsules are ‘very reasonable’

For people who either can’t consume two fish meals a week or want to ensure their omega 3 intake is adequate, “it’s very reasonable for the average person to take one OTC [over-the-counter] fish oil capsule a day,” Dr. Mozaffarian added.

He acknowledged that several studies of fish oil supplements failed to show benefit, but several others have. “It’s a confusing field, but the evidence supports benefit from omega 3s,” he concluded.

He discounted the new finding that only people with established CVD or who are at high-risk benefit. “I’m not sure we should make too much of this, because many prior studies showed a lower CVD risk in fish-eating people without prevalent CVD,” he said. The new study “provides important information given its worldwide breadth.”

The new report used data regarding 191,558 people enrolled prospectively in any of four studies. The average age of the participants was 54 years, and 52% were women.

During follow-up, death from any cause occurred in 6% of those without CVD or CVD risk and in 13% of those with these factors. Major CVD events occurred in 5% and 17% of these two subgroups, respectively. To calculate the relative risks between those who ate fish and those who did not, the investigators used standard multivariate adjustment for potential confounders and adjusted for several dietary variables, Dr. Mente said.

Dr. Mohan and Dr. Mente disclosed no relevant financial relationships. Dr. Mozaffarian has received personal fees from Acasti Pharma, Amarin, America’s Test Kitchen, Barilla, Danone, GEOD, and Motif Food Works, and he has been an adviser to numerous companies.

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

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

Being obese and pregnant raises the risk for cardiac complications in women with preexisting heart disease, new research suggests, highlighting the need for earlier interventions in this high-risk population.

The analysis of 790 pregnancies revealed that 23% of women with obesity, defined as body mass index greater than 30 kg/m2, had a cardiac event during pregnancy versus 14% of women with normal body weight (P = .006).

The difference was driven largely by an increase in heart failure (8% vs. 3%; P = .02), although arrhythmias also trended higher in obese women (14% vs. 10%; P = .19).

Nearly half of the women with obesity and a cardiac event presented in the postpartum period (47%).

In multivariate analysis, both obesity and Canadian Cardiac Disease in Pregnancy Study (CARPREG) II risk score were independent predictors of cardiac events (odds ratios for both, 1.7), the investigators, led by Birgit Pfaller, MD, University of Toronto, reported in the Journal of the American College of Cardiology.

Although obesity has been linked to worse pregnancy outcomes and higher cardiovascular risk after delivery in the general population, the authors noted that this is the first study to examine its effect on outcomes in women with heart disease.

“We wanted to look at this high-risk group of women that had preexisting heart disease, but in addition had obesity, to try and find out if there was a kind of double hit for these women – and that, in the end, is what we found. It’s not just simply having heart disease, not simply having obesity, but the combination that’s problematic,” senior author and cardiologist Candice Silversides, MD, University of Toronto, said in an interview.

The findings are concerning given the rising prevalence of obesity worldwide. National data from 2018 show that slightly more than half of women who gave birth in the United States were significantly overweight or obese before becoming pregnant.

Similarly, in the present analysis of 600 women in the CARPREG study who gave birth from 2004 to 2014, nearly 1 in 5 pregnancies (19%) occurred in women with obesity and 25% were in overweight women.

Obese women were significantly more likely than those without obesity to have coronary artery disease (6% vs. 2%), cardiomyopathies (19% vs. 8%) and left ventricular dysfunction (19% vs. 12%) and to be hypertensive or have a hypertensive disorder of pregnancy (13% vs. 3%).

Preeclampsia developed in 32 women during the index pregnancy and 69% of these women were obese or overweight. Cardiac event rates were similar in women with or without preeclampsia but trended higher in women with preeclampsia with versus without obesity (36% vs. 14%; P = .20).

The ill effects of obesity were also reflected in fetal and neonatal events. Overall, 43% of women with obesity and 33% of normal-weight women had at least one fetal event (P = .02), with higher rates of preterm birth (19% vs. 10%; P = .005) and respiratory distress syndrome (8% vs. 3%; P = .02) in women with obesity. Congenital cardiac malformations were present in 6% of women in both groups.

Taken together, the composite of cardiac events, preeclampsia, or fetal events was significantly more common in women with obesity than in normal-weight women (56% vs. 41%; P = .002).

“We’ve spent the last number of years trying to research and understand what the drivers of these adverse outcomes are in this high-risk pregnant cohort, but on a bigger picture the real issue is how do we start intervening in a meaningful way,” Dr. Silversides said.

Like many in the burgeoning field of cardio-obstetrics, the team proposed a multidisciplinary approach that stresses preconception counseling, educating pregnant women with heart disease and obesity about their risks, ensuring that dietary advice, weight-gain recommendations, and comorbidities are addressed as part of routine care, and providing postpartum surveillance.

Preconception screening “has been the recommendation for a long, long time; it’s just that it doesn’t always happen in reality,” she said. “Many pregnancies aren’t planned and not all women are filtered into preconception counseling. So sometimes you’ll do it at the first antenatal visit and try to ensure women are educated but optimally you want to do it well in advance of pregnancy.”

Part of that preconception counseling “should also include giving them appropriate advice for contraception, if what they want to do is avoid pregnancy,” added Dr. Silversides.

Garima Sharma, MD, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, and colleagues wrote in an accompanying editorial that the adverse events observed in this high-risk cohort have “important implications for cardio-obstetricians and should be incorporated in routine prepregnancy and antenatal counseling, monitoring, and risk stratification for women with existing cardiovascular disease.”

They pointed to a paucity of data incorporating maternal prepregnancy obesity and gestational weight gain in risk prediction and called for larger population-based studies on the additive impact of obesity severity on predicting adverse cardiac events in women with existing cardiovascular disease.

Randomized trials are also urgently needed to evaluate the effect of nutritional and behavioral interventions in pregnancy on short- and long-term outcomes in mother and child.

“As the obesity epidemic continues to grow and public health interventions promoting lifestyle changes for obesity management remain a major challenge, maternal obesity may prove to be the ‘Achilles’ heel’ of sustainable national efforts to reduce maternal mortality and improve health equity. This is a call to action,” Dr. Sharma and colleagues concluded.

The investigators noted that the study was conducted at a single center and used self-reported pregnancy weight collected at the first antenatal visit, which may have underestimated obesity rates. Other limitations are that weight changes over the course of pregnancy were not studied and there was a limited number of women with a body mass index of 40 or higher.

The study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation, and by a donation from Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. Dr. Sharma and colleagues disclosed no relevant financial relationships.

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

Being obese and pregnant raises the risk for cardiac complications in women with preexisting heart disease, new research suggests, highlighting the need for earlier interventions in this high-risk population.

The analysis of 790 pregnancies revealed that 23% of women with obesity, defined as body mass index greater than 30 kg/m2, had a cardiac event during pregnancy versus 14% of women with normal body weight (P = .006).

The difference was driven largely by an increase in heart failure (8% vs. 3%; P = .02), although arrhythmias also trended higher in obese women (14% vs. 10%; P = .19).

Nearly half of the women with obesity and a cardiac event presented in the postpartum period (47%).

In multivariate analysis, both obesity and Canadian Cardiac Disease in Pregnancy Study (CARPREG) II risk score were independent predictors of cardiac events (odds ratios for both, 1.7), the investigators, led by Birgit Pfaller, MD, University of Toronto, reported in the Journal of the American College of Cardiology.

Although obesity has been linked to worse pregnancy outcomes and higher cardiovascular risk after delivery in the general population, the authors noted that this is the first study to examine its effect on outcomes in women with heart disease.

“We wanted to look at this high-risk group of women that had preexisting heart disease, but in addition had obesity, to try and find out if there was a kind of double hit for these women – and that, in the end, is what we found. It’s not just simply having heart disease, not simply having obesity, but the combination that’s problematic,” senior author and cardiologist Candice Silversides, MD, University of Toronto, said in an interview.

The findings are concerning given the rising prevalence of obesity worldwide. National data from 2018 show that slightly more than half of women who gave birth in the United States were significantly overweight or obese before becoming pregnant.

Similarly, in the present analysis of 600 women in the CARPREG study who gave birth from 2004 to 2014, nearly 1 in 5 pregnancies (19%) occurred in women with obesity and 25% were in overweight women.

Obese women were significantly more likely than those without obesity to have coronary artery disease (6% vs. 2%), cardiomyopathies (19% vs. 8%) and left ventricular dysfunction (19% vs. 12%) and to be hypertensive or have a hypertensive disorder of pregnancy (13% vs. 3%).

Preeclampsia developed in 32 women during the index pregnancy and 69% of these women were obese or overweight. Cardiac event rates were similar in women with or without preeclampsia but trended higher in women with preeclampsia with versus without obesity (36% vs. 14%; P = .20).

The ill effects of obesity were also reflected in fetal and neonatal events. Overall, 43% of women with obesity and 33% of normal-weight women had at least one fetal event (P = .02), with higher rates of preterm birth (19% vs. 10%; P = .005) and respiratory distress syndrome (8% vs. 3%; P = .02) in women with obesity. Congenital cardiac malformations were present in 6% of women in both groups.

Taken together, the composite of cardiac events, preeclampsia, or fetal events was significantly more common in women with obesity than in normal-weight women (56% vs. 41%; P = .002).

“We’ve spent the last number of years trying to research and understand what the drivers of these adverse outcomes are in this high-risk pregnant cohort, but on a bigger picture the real issue is how do we start intervening in a meaningful way,” Dr. Silversides said.

Like many in the burgeoning field of cardio-obstetrics, the team proposed a multidisciplinary approach that stresses preconception counseling, educating pregnant women with heart disease and obesity about their risks, ensuring that dietary advice, weight-gain recommendations, and comorbidities are addressed as part of routine care, and providing postpartum surveillance.

Preconception screening “has been the recommendation for a long, long time; it’s just that it doesn’t always happen in reality,” she said. “Many pregnancies aren’t planned and not all women are filtered into preconception counseling. So sometimes you’ll do it at the first antenatal visit and try to ensure women are educated but optimally you want to do it well in advance of pregnancy.”

Part of that preconception counseling “should also include giving them appropriate advice for contraception, if what they want to do is avoid pregnancy,” added Dr. Silversides.

Garima Sharma, MD, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, and colleagues wrote in an accompanying editorial that the adverse events observed in this high-risk cohort have “important implications for cardio-obstetricians and should be incorporated in routine prepregnancy and antenatal counseling, monitoring, and risk stratification for women with existing cardiovascular disease.”

They pointed to a paucity of data incorporating maternal prepregnancy obesity and gestational weight gain in risk prediction and called for larger population-based studies on the additive impact of obesity severity on predicting adverse cardiac events in women with existing cardiovascular disease.

Randomized trials are also urgently needed to evaluate the effect of nutritional and behavioral interventions in pregnancy on short- and long-term outcomes in mother and child.

“As the obesity epidemic continues to grow and public health interventions promoting lifestyle changes for obesity management remain a major challenge, maternal obesity may prove to be the ‘Achilles’ heel’ of sustainable national efforts to reduce maternal mortality and improve health equity. This is a call to action,” Dr. Sharma and colleagues concluded.

The investigators noted that the study was conducted at a single center and used self-reported pregnancy weight collected at the first antenatal visit, which may have underestimated obesity rates. Other limitations are that weight changes over the course of pregnancy were not studied and there was a limited number of women with a body mass index of 40 or higher.

The study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation, and by a donation from Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. Dr. Sharma and colleagues disclosed no relevant financial relationships.

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

Being obese and pregnant raises the risk for cardiac complications in women with preexisting heart disease, new research suggests, highlighting the need for earlier interventions in this high-risk population.

The analysis of 790 pregnancies revealed that 23% of women with obesity, defined as body mass index greater than 30 kg/m2, had a cardiac event during pregnancy versus 14% of women with normal body weight (P = .006).

The difference was driven largely by an increase in heart failure (8% vs. 3%; P = .02), although arrhythmias also trended higher in obese women (14% vs. 10%; P = .19).

Nearly half of the women with obesity and a cardiac event presented in the postpartum period (47%).

In multivariate analysis, both obesity and Canadian Cardiac Disease in Pregnancy Study (CARPREG) II risk score were independent predictors of cardiac events (odds ratios for both, 1.7), the investigators, led by Birgit Pfaller, MD, University of Toronto, reported in the Journal of the American College of Cardiology.

Although obesity has been linked to worse pregnancy outcomes and higher cardiovascular risk after delivery in the general population, the authors noted that this is the first study to examine its effect on outcomes in women with heart disease.

“We wanted to look at this high-risk group of women that had preexisting heart disease, but in addition had obesity, to try and find out if there was a kind of double hit for these women – and that, in the end, is what we found. It’s not just simply having heart disease, not simply having obesity, but the combination that’s problematic,” senior author and cardiologist Candice Silversides, MD, University of Toronto, said in an interview.

The findings are concerning given the rising prevalence of obesity worldwide. National data from 2018 show that slightly more than half of women who gave birth in the United States were significantly overweight or obese before becoming pregnant.

Similarly, in the present analysis of 600 women in the CARPREG study who gave birth from 2004 to 2014, nearly 1 in 5 pregnancies (19%) occurred in women with obesity and 25% were in overweight women.

Obese women were significantly more likely than those without obesity to have coronary artery disease (6% vs. 2%), cardiomyopathies (19% vs. 8%) and left ventricular dysfunction (19% vs. 12%) and to be hypertensive or have a hypertensive disorder of pregnancy (13% vs. 3%).

Preeclampsia developed in 32 women during the index pregnancy and 69% of these women were obese or overweight. Cardiac event rates were similar in women with or without preeclampsia but trended higher in women with preeclampsia with versus without obesity (36% vs. 14%; P = .20).

The ill effects of obesity were also reflected in fetal and neonatal events. Overall, 43% of women with obesity and 33% of normal-weight women had at least one fetal event (P = .02), with higher rates of preterm birth (19% vs. 10%; P = .005) and respiratory distress syndrome (8% vs. 3%; P = .02) in women with obesity. Congenital cardiac malformations were present in 6% of women in both groups.

Taken together, the composite of cardiac events, preeclampsia, or fetal events was significantly more common in women with obesity than in normal-weight women (56% vs. 41%; P = .002).

“We’ve spent the last number of years trying to research and understand what the drivers of these adverse outcomes are in this high-risk pregnant cohort, but on a bigger picture the real issue is how do we start intervening in a meaningful way,” Dr. Silversides said.

Like many in the burgeoning field of cardio-obstetrics, the team proposed a multidisciplinary approach that stresses preconception counseling, educating pregnant women with heart disease and obesity about their risks, ensuring that dietary advice, weight-gain recommendations, and comorbidities are addressed as part of routine care, and providing postpartum surveillance.

Preconception screening “has been the recommendation for a long, long time; it’s just that it doesn’t always happen in reality,” she said. “Many pregnancies aren’t planned and not all women are filtered into preconception counseling. So sometimes you’ll do it at the first antenatal visit and try to ensure women are educated but optimally you want to do it well in advance of pregnancy.”

Part of that preconception counseling “should also include giving them appropriate advice for contraception, if what they want to do is avoid pregnancy,” added Dr. Silversides.

Garima Sharma, MD, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, and colleagues wrote in an accompanying editorial that the adverse events observed in this high-risk cohort have “important implications for cardio-obstetricians and should be incorporated in routine prepregnancy and antenatal counseling, monitoring, and risk stratification for women with existing cardiovascular disease.”

They pointed to a paucity of data incorporating maternal prepregnancy obesity and gestational weight gain in risk prediction and called for larger population-based studies on the additive impact of obesity severity on predicting adverse cardiac events in women with existing cardiovascular disease.

Randomized trials are also urgently needed to evaluate the effect of nutritional and behavioral interventions in pregnancy on short- and long-term outcomes in mother and child.

“As the obesity epidemic continues to grow and public health interventions promoting lifestyle changes for obesity management remain a major challenge, maternal obesity may prove to be the ‘Achilles’ heel’ of sustainable national efforts to reduce maternal mortality and improve health equity. This is a call to action,” Dr. Sharma and colleagues concluded.

The investigators noted that the study was conducted at a single center and used self-reported pregnancy weight collected at the first antenatal visit, which may have underestimated obesity rates. Other limitations are that weight changes over the course of pregnancy were not studied and there was a limited number of women with a body mass index of 40 or higher.

The study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation, and by a donation from Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. Dr. Sharma and colleagues disclosed no relevant financial relationships.

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