Cardiology

TOPLINE:

The cardiovascular benefits observed with intensive blood pressure (BP) control in patients with hypertension and elevated cardiovascular risk from the Systolic Blood Pressure Intervention Trial (SPRINT) can be largely replicated in real-world settings among patients with chronic kidney disease (CKD), highlighting the advantages of adopting intensive BP targets.
 

METHODOLOGY:

• The SPRINT showed that an intensive systolic BP goal < 120 mm Hg reduced mortality, cardiovascular events, and mild cognitive impairment in patients with hypertension and elevated cardiovascular risk, including in patients with CKD.
• Researchers conducted a comparative effectiveness study to determine if the beneficial and adverse effects of intensive vs standard BP control observed in SPRINT were replicable in patients with CKD and hypertension in clinical practice.
• They identified 85,938 patients (mean age, 75.7 years; 95.0% men) and 13,983 patients (mean age, 77.4 years; 38.4% men) from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) databases, respectively.
• The treatment effect was estimated by combining baseline covariate, treatment, and outcome data of participants from the SPRINT with covariate data from the VHA and KPSC databases.
• The primary outcomes included major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.

TAKEAWAY:

• Compared with SPRINT participants, those in the VHA and KPSC databases were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins.
• The benefits of intensive vs standard BP control on major cardiovascular events, all-cause mortality, and certain adverse events (hypotension, syncope, bradycardia, acute kidney injury, and electrolyte abnormality) were transferable from the trial to the VHA and KPSC populations.
• The treatment effect of intensive BP management on CKD progression was transportable to the KPSC population but not to the VHA population. However, the trial’s impact on cognitive outcomes, such as dementia, was not transportable to either the VHA or KPSC populations.
• On the absolute scale, intensive vs standard BP treatment showed greater cardiovascular benefits and fewer safety concerns in the VHA and KPSC populations than in the SPRINT.

IN PRACTICE:

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” the authors wrote.
 

SOURCE:

This study was led by Manjula Kurella Tamura, MD, MPH, Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California. It was published online on January 7, 2025, in JAMA Network Open.
 

LIMITATIONS:

Transportability analyses could not account for characteristics that were not well-documented in electronic health records, such as limited life expectancy. The study was conducted before the widespread use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, making it unclear whether intensive BP treatment would result in similar benefits with current pharmacotherapy regimens. Eligibility for this study was based on BP measurements in routine practice, which tend to be more variable than those collected in research settings.
 

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors disclosed serving as a consultant and receiving grants, personal fees, and consulting fees from pharmaceutical companies and other sources.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The cardiovascular benefits observed with intensive blood pressure (BP) control in patients with hypertension and elevated cardiovascular risk from the Systolic Blood Pressure Intervention Trial (SPRINT) can be largely replicated in real-world settings among patients with chronic kidney disease (CKD), highlighting the advantages of adopting intensive BP targets.
 

METHODOLOGY:

• The SPRINT showed that an intensive systolic BP goal < 120 mm Hg reduced mortality, cardiovascular events, and mild cognitive impairment in patients with hypertension and elevated cardiovascular risk, including in patients with CKD.
• Researchers conducted a comparative effectiveness study to determine if the beneficial and adverse effects of intensive vs standard BP control observed in SPRINT were replicable in patients with CKD and hypertension in clinical practice.
• They identified 85,938 patients (mean age, 75.7 years; 95.0% men) and 13,983 patients (mean age, 77.4 years; 38.4% men) from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) databases, respectively.
• The treatment effect was estimated by combining baseline covariate, treatment, and outcome data of participants from the SPRINT with covariate data from the VHA and KPSC databases.
• The primary outcomes included major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.

TAKEAWAY:

• Compared with SPRINT participants, those in the VHA and KPSC databases were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins.
• The benefits of intensive vs standard BP control on major cardiovascular events, all-cause mortality, and certain adverse events (hypotension, syncope, bradycardia, acute kidney injury, and electrolyte abnormality) were transferable from the trial to the VHA and KPSC populations.
• The treatment effect of intensive BP management on CKD progression was transportable to the KPSC population but not to the VHA population. However, the trial’s impact on cognitive outcomes, such as dementia, was not transportable to either the VHA or KPSC populations.
• On the absolute scale, intensive vs standard BP treatment showed greater cardiovascular benefits and fewer safety concerns in the VHA and KPSC populations than in the SPRINT.

IN PRACTICE:

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” the authors wrote.
 

SOURCE:

This study was led by Manjula Kurella Tamura, MD, MPH, Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California. It was published online on January 7, 2025, in JAMA Network Open.
 

LIMITATIONS:

Transportability analyses could not account for characteristics that were not well-documented in electronic health records, such as limited life expectancy. The study was conducted before the widespread use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, making it unclear whether intensive BP treatment would result in similar benefits with current pharmacotherapy regimens. Eligibility for this study was based on BP measurements in routine practice, which tend to be more variable than those collected in research settings.
 

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors disclosed serving as a consultant and receiving grants, personal fees, and consulting fees from pharmaceutical companies and other sources.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The cardiovascular benefits observed with intensive blood pressure (BP) control in patients with hypertension and elevated cardiovascular risk from the Systolic Blood Pressure Intervention Trial (SPRINT) can be largely replicated in real-world settings among patients with chronic kidney disease (CKD), highlighting the advantages of adopting intensive BP targets.
 

METHODOLOGY:

• The SPRINT showed that an intensive systolic BP goal < 120 mm Hg reduced mortality, cardiovascular events, and mild cognitive impairment in patients with hypertension and elevated cardiovascular risk, including in patients with CKD.
• Researchers conducted a comparative effectiveness study to determine if the beneficial and adverse effects of intensive vs standard BP control observed in SPRINT were replicable in patients with CKD and hypertension in clinical practice.
• They identified 85,938 patients (mean age, 75.7 years; 95.0% men) and 13,983 patients (mean age, 77.4 years; 38.4% men) from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) databases, respectively.
• The treatment effect was estimated by combining baseline covariate, treatment, and outcome data of participants from the SPRINT with covariate data from the VHA and KPSC databases.
• The primary outcomes included major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.

TAKEAWAY:

• Compared with SPRINT participants, those in the VHA and KPSC databases were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins.
• The benefits of intensive vs standard BP control on major cardiovascular events, all-cause mortality, and certain adverse events (hypotension, syncope, bradycardia, acute kidney injury, and electrolyte abnormality) were transferable from the trial to the VHA and KPSC populations.
• The treatment effect of intensive BP management on CKD progression was transportable to the KPSC population but not to the VHA population. However, the trial’s impact on cognitive outcomes, such as dementia, was not transportable to either the VHA or KPSC populations.
• On the absolute scale, intensive vs standard BP treatment showed greater cardiovascular benefits and fewer safety concerns in the VHA and KPSC populations than in the SPRINT.

IN PRACTICE:

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” the authors wrote.
 

SOURCE:

This study was led by Manjula Kurella Tamura, MD, MPH, Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California. It was published online on January 7, 2025, in JAMA Network Open.
 

LIMITATIONS:

Transportability analyses could not account for characteristics that were not well-documented in electronic health records, such as limited life expectancy. The study was conducted before the widespread use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, making it unclear whether intensive BP treatment would result in similar benefits with current pharmacotherapy regimens. Eligibility for this study was based on BP measurements in routine practice, which tend to be more variable than those collected in research settings.
 

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors disclosed serving as a consultant and receiving grants, personal fees, and consulting fees from pharmaceutical companies and other sources.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Blood pressure. If you’re a primary care provider trying to do right by your patients, you might be understandably confused by the current mishmash of guidelines with different blood pressure targets. But as chaotic as things are, at least it’s not the 1930s, when you might hear John Hay give a lecture to the British Medical Association and say, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.”

Yeah, he said that. But what happened in the 1930s stays in the 1930s. And now we can at least agree that we should be treating high blood pressure. But what’s the goal we should be aiming for? This is On Second Thought. 

We’ve come a long way since FDR was recording blood pressures of 200 and his doctor prescribed him barbiturates and massage therapy.

That s#$# don’t fly no more. Over the past hundred years, we have become much more aggressive in treating blood pressure. Remember the Oslo study? It defined mild hypertension as a blood pressure between 150 and 180 mm Hg. Now, those numbers send people screaming to the emergency room. So, let’s acknowledge that things are substantially better than they once were. Let’s agree on that and we can start to heal this nation again. 

Before we get into the numbers, when we’re treating blood pressure, let’s make a few points about measuring it. Obviously, to treat something, you have to measure it properly. Two recent trials have illustrated that these details matter a lot.

The Cuff(SZ) randomized crossover trial — and it took me a minute to realize that Cuff(SZ) meant cuff size, so bravo, Ishigami et al — showed that picking the wrong cuff size could affect BP measurements by 4.5 points if you were one size off. If you were two sizes too small, you overestimated BP by almost 20 points.

Add on here another recent study, the ARMS crossover randomized clinical trial, looking at how arm position affected BP measures. If the arm was resting on your lap or hanging by your side, that overestimated blood pressure by 4 and 6.5 points. So sometimes you have to remember the fundamentals: cuff size, arm position — it might make the difference between increasing or maintaining the patient’s meds.

But on to the main show. What numbers should we be aiming for? We no longer live in the “BP 200, the president’s going to have a stroke” world of the 1940s, and even a BP of 150 is considered quite high these days. Studies like the MRC trial, INVEST, and SPRINT have pushed BP targets ever lower. SPRINT, in particular, randomized patients to a blood pressure target under 120 systolic vs under 140 systolic, and the under-120 arm won out with fewer cardiovascular events and lower all-cause mortality.

Pretty definitive slam dunk. But the more intensive treatment came with more hypotension, syncope, and kidney injury, because there is no free lunch in medicine. And ditto with BPROAD, just published in The New England Journal of Medicine and presented at the American Heart Association annual meeting. A diabetic population randomized to 120 vs 140 as a BP target showed that more aggressive treatment was better.

Fewer cardiovascular events, like stroke, but no mortality difference, and more hypotension. So a cardiovascular benefit at the cost of more side effects. Now, like all cardiologists, my motto is “Save the heart and screw the kidney.” But if you do care about the other organs in this meat sack that we call a human body, the question you need to wrestle with is, how much do you value cardiovascular protection vs how willing are you to tolerate side effects?

Hypotension may not sound dangerous, but gravity is an unforgiving mistress. If you painstakingly compile the summary of the various BP guidelines for easy perusal, you would notice something critical: One, I have too much free time on my hands; two, the disagreements are not really all that profound.

Arguing about 120 vs 130 vs 140 is not the same as saying, “Drugs schmugs; a good massage will fix what ails you, and here are some addictive sleeping pills for good measure.” Physicians from the 1930s were a little sketchy. So much of this controversy is about how you define high-risk patients and what are the age cutoffs.

Basically, the cardiovascular guidelines say, “Treat them all and let God sort it out” because they care about cardiovascular events and are concerned about cardiovascular endpoints. Whereas general practice guidelines put more emphasis on potential side effects and admittedly tend to treat a not so high-risk population, so they have laxer targets.

A 2014 analysis from the Blood Pressure Lowering Treatment Trialists’ Collaboration [The Lancet] had a good mathematical way of explaining this problem. Now, lowering blood pressure is obviously a good thing. That prevents heart attacks, strokes, kidney failure, and all that. Please don’t let hypertension denialism become a thing.

Let’s start with the basics. Treating high blood pressure led to a 15% to 18% decrease in cardiovascular events, pretty consistently across all risk categories, and other analyses have found that every 5-point decrease in blood pressure gives you about a 10% decrease in major cardiovascular events on the relative-risk scale. 

While the benefits are pretty consistent across all groups, that difference in baseline risk translates into different absolute benefits. In the Lancet paper, when the population was divided into four different groups based on their cardiovascular risk, the absolute risk reduction in the lowest-risk group was 14 fewer cardiovascular events if you treat 1000 patients for 5 years.

With each higher-risk group, it was 20 fewer, 24 fewer, and 38 fewer. At the lowest-risk group, the number needed to treat was 71, 50, 42, and 26 fewer cardiovascular events with 5 years of treatment. 

And herein lies the secret to the disagreement: If you have a high-risk patient, there is a big benefit to bringing that blood pressure down from 135 to 130. Whereas for a low-risk patient, it probably doesn’t matter as much. And the cardiovascular benefits are going to be offset by the side effects and the risks for hypotension. 

Of course, there’s a simple solution to this dilemma: Just speak to the patient in front of you. Treat high blood pressure, and if your patient’s blood pressure drops or they get dizzy or have fainting spells, then just ease up on the meds. It’s not rocket science; it’s just cardiology. 

Arguing about five millimeters of mercury of blood pressure is probably less important from the public health perspective than the fact that tens of millions of people in the United States are unaware that they have hypertension, and even those diagnosed are being inadequately treated.

So, let’s all do better as a medical community. Nobody should have untreated hypertension in this day and age. It’s not the 1930s. 
 

Dr Labos, Cardiologist, Kirkland Medical Center, Montreal, Quebec, Canada, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Blood pressure. If you’re a primary care provider trying to do right by your patients, you might be understandably confused by the current mishmash of guidelines with different blood pressure targets. But as chaotic as things are, at least it’s not the 1930s, when you might hear John Hay give a lecture to the British Medical Association and say, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.”

Yeah, he said that. But what happened in the 1930s stays in the 1930s. And now we can at least agree that we should be treating high blood pressure. But what’s the goal we should be aiming for? This is On Second Thought. 

We’ve come a long way since FDR was recording blood pressures of 200 and his doctor prescribed him barbiturates and massage therapy.

That s#$# don’t fly no more. Over the past hundred years, we have become much more aggressive in treating blood pressure. Remember the Oslo study? It defined mild hypertension as a blood pressure between 150 and 180 mm Hg. Now, those numbers send people screaming to the emergency room. So, let’s acknowledge that things are substantially better than they once were. Let’s agree on that and we can start to heal this nation again. 

Before we get into the numbers, when we’re treating blood pressure, let’s make a few points about measuring it. Obviously, to treat something, you have to measure it properly. Two recent trials have illustrated that these details matter a lot.

The Cuff(SZ) randomized crossover trial — and it took me a minute to realize that Cuff(SZ) meant cuff size, so bravo, Ishigami et al — showed that picking the wrong cuff size could affect BP measurements by 4.5 points if you were one size off. If you were two sizes too small, you overestimated BP by almost 20 points.

Add on here another recent study, the ARMS crossover randomized clinical trial, looking at how arm position affected BP measures. If the arm was resting on your lap or hanging by your side, that overestimated blood pressure by 4 and 6.5 points. So sometimes you have to remember the fundamentals: cuff size, arm position — it might make the difference between increasing or maintaining the patient’s meds.

But on to the main show. What numbers should we be aiming for? We no longer live in the “BP 200, the president’s going to have a stroke” world of the 1940s, and even a BP of 150 is considered quite high these days. Studies like the MRC trial, INVEST, and SPRINT have pushed BP targets ever lower. SPRINT, in particular, randomized patients to a blood pressure target under 120 systolic vs under 140 systolic, and the under-120 arm won out with fewer cardiovascular events and lower all-cause mortality.

Pretty definitive slam dunk. But the more intensive treatment came with more hypotension, syncope, and kidney injury, because there is no free lunch in medicine. And ditto with BPROAD, just published in The New England Journal of Medicine and presented at the American Heart Association annual meeting. A diabetic population randomized to 120 vs 140 as a BP target showed that more aggressive treatment was better.

Fewer cardiovascular events, like stroke, but no mortality difference, and more hypotension. So a cardiovascular benefit at the cost of more side effects. Now, like all cardiologists, my motto is “Save the heart and screw the kidney.” But if you do care about the other organs in this meat sack that we call a human body, the question you need to wrestle with is, how much do you value cardiovascular protection vs how willing are you to tolerate side effects?

Hypotension may not sound dangerous, but gravity is an unforgiving mistress. If you painstakingly compile the summary of the various BP guidelines for easy perusal, you would notice something critical: One, I have too much free time on my hands; two, the disagreements are not really all that profound.

Arguing about 120 vs 130 vs 140 is not the same as saying, “Drugs schmugs; a good massage will fix what ails you, and here are some addictive sleeping pills for good measure.” Physicians from the 1930s were a little sketchy. So much of this controversy is about how you define high-risk patients and what are the age cutoffs.

Basically, the cardiovascular guidelines say, “Treat them all and let God sort it out” because they care about cardiovascular events and are concerned about cardiovascular endpoints. Whereas general practice guidelines put more emphasis on potential side effects and admittedly tend to treat a not so high-risk population, so they have laxer targets.

A 2014 analysis from the Blood Pressure Lowering Treatment Trialists’ Collaboration [The Lancet] had a good mathematical way of explaining this problem. Now, lowering blood pressure is obviously a good thing. That prevents heart attacks, strokes, kidney failure, and all that. Please don’t let hypertension denialism become a thing.

Let’s start with the basics. Treating high blood pressure led to a 15% to 18% decrease in cardiovascular events, pretty consistently across all risk categories, and other analyses have found that every 5-point decrease in blood pressure gives you about a 10% decrease in major cardiovascular events on the relative-risk scale. 

While the benefits are pretty consistent across all groups, that difference in baseline risk translates into different absolute benefits. In the Lancet paper, when the population was divided into four different groups based on their cardiovascular risk, the absolute risk reduction in the lowest-risk group was 14 fewer cardiovascular events if you treat 1000 patients for 5 years.

With each higher-risk group, it was 20 fewer, 24 fewer, and 38 fewer. At the lowest-risk group, the number needed to treat was 71, 50, 42, and 26 fewer cardiovascular events with 5 years of treatment. 

And herein lies the secret to the disagreement: If you have a high-risk patient, there is a big benefit to bringing that blood pressure down from 135 to 130. Whereas for a low-risk patient, it probably doesn’t matter as much. And the cardiovascular benefits are going to be offset by the side effects and the risks for hypotension. 

Of course, there’s a simple solution to this dilemma: Just speak to the patient in front of you. Treat high blood pressure, and if your patient’s blood pressure drops or they get dizzy or have fainting spells, then just ease up on the meds. It’s not rocket science; it’s just cardiology. 

Arguing about five millimeters of mercury of blood pressure is probably less important from the public health perspective than the fact that tens of millions of people in the United States are unaware that they have hypertension, and even those diagnosed are being inadequately treated.

So, let’s all do better as a medical community. Nobody should have untreated hypertension in this day and age. It’s not the 1930s. 
 

Dr Labos, Cardiologist, Kirkland Medical Center, Montreal, Quebec, Canada, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Blood pressure. If you’re a primary care provider trying to do right by your patients, you might be understandably confused by the current mishmash of guidelines with different blood pressure targets. But as chaotic as things are, at least it’s not the 1930s, when you might hear John Hay give a lecture to the British Medical Association and say, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.”

Yeah, he said that. But what happened in the 1930s stays in the 1930s. And now we can at least agree that we should be treating high blood pressure. But what’s the goal we should be aiming for? This is On Second Thought. 

We’ve come a long way since FDR was recording blood pressures of 200 and his doctor prescribed him barbiturates and massage therapy.

That s#$# don’t fly no more. Over the past hundred years, we have become much more aggressive in treating blood pressure. Remember the Oslo study? It defined mild hypertension as a blood pressure between 150 and 180 mm Hg. Now, those numbers send people screaming to the emergency room. So, let’s acknowledge that things are substantially better than they once were. Let’s agree on that and we can start to heal this nation again. 

Before we get into the numbers, when we’re treating blood pressure, let’s make a few points about measuring it. Obviously, to treat something, you have to measure it properly. Two recent trials have illustrated that these details matter a lot.

The Cuff(SZ) randomized crossover trial — and it took me a minute to realize that Cuff(SZ) meant cuff size, so bravo, Ishigami et al — showed that picking the wrong cuff size could affect BP measurements by 4.5 points if you were one size off. If you were two sizes too small, you overestimated BP by almost 20 points.

Add on here another recent study, the ARMS crossover randomized clinical trial, looking at how arm position affected BP measures. If the arm was resting on your lap or hanging by your side, that overestimated blood pressure by 4 and 6.5 points. So sometimes you have to remember the fundamentals: cuff size, arm position — it might make the difference between increasing or maintaining the patient’s meds.

But on to the main show. What numbers should we be aiming for? We no longer live in the “BP 200, the president’s going to have a stroke” world of the 1940s, and even a BP of 150 is considered quite high these days. Studies like the MRC trial, INVEST, and SPRINT have pushed BP targets ever lower. SPRINT, in particular, randomized patients to a blood pressure target under 120 systolic vs under 140 systolic, and the under-120 arm won out with fewer cardiovascular events and lower all-cause mortality.

Pretty definitive slam dunk. But the more intensive treatment came with more hypotension, syncope, and kidney injury, because there is no free lunch in medicine. And ditto with BPROAD, just published in The New England Journal of Medicine and presented at the American Heart Association annual meeting. A diabetic population randomized to 120 vs 140 as a BP target showed that more aggressive treatment was better.

Fewer cardiovascular events, like stroke, but no mortality difference, and more hypotension. So a cardiovascular benefit at the cost of more side effects. Now, like all cardiologists, my motto is “Save the heart and screw the kidney.” But if you do care about the other organs in this meat sack that we call a human body, the question you need to wrestle with is, how much do you value cardiovascular protection vs how willing are you to tolerate side effects?

Hypotension may not sound dangerous, but gravity is an unforgiving mistress. If you painstakingly compile the summary of the various BP guidelines for easy perusal, you would notice something critical: One, I have too much free time on my hands; two, the disagreements are not really all that profound.

Arguing about 120 vs 130 vs 140 is not the same as saying, “Drugs schmugs; a good massage will fix what ails you, and here are some addictive sleeping pills for good measure.” Physicians from the 1930s were a little sketchy. So much of this controversy is about how you define high-risk patients and what are the age cutoffs.

Basically, the cardiovascular guidelines say, “Treat them all and let God sort it out” because they care about cardiovascular events and are concerned about cardiovascular endpoints. Whereas general practice guidelines put more emphasis on potential side effects and admittedly tend to treat a not so high-risk population, so they have laxer targets.

A 2014 analysis from the Blood Pressure Lowering Treatment Trialists’ Collaboration [The Lancet] had a good mathematical way of explaining this problem. Now, lowering blood pressure is obviously a good thing. That prevents heart attacks, strokes, kidney failure, and all that. Please don’t let hypertension denialism become a thing.

Let’s start with the basics. Treating high blood pressure led to a 15% to 18% decrease in cardiovascular events, pretty consistently across all risk categories, and other analyses have found that every 5-point decrease in blood pressure gives you about a 10% decrease in major cardiovascular events on the relative-risk scale. 

While the benefits are pretty consistent across all groups, that difference in baseline risk translates into different absolute benefits. In the Lancet paper, when the population was divided into four different groups based on their cardiovascular risk, the absolute risk reduction in the lowest-risk group was 14 fewer cardiovascular events if you treat 1000 patients for 5 years.

With each higher-risk group, it was 20 fewer, 24 fewer, and 38 fewer. At the lowest-risk group, the number needed to treat was 71, 50, 42, and 26 fewer cardiovascular events with 5 years of treatment. 

And herein lies the secret to the disagreement: If you have a high-risk patient, there is a big benefit to bringing that blood pressure down from 135 to 130. Whereas for a low-risk patient, it probably doesn’t matter as much. And the cardiovascular benefits are going to be offset by the side effects and the risks for hypotension. 

Of course, there’s a simple solution to this dilemma: Just speak to the patient in front of you. Treat high blood pressure, and if your patient’s blood pressure drops or they get dizzy or have fainting spells, then just ease up on the meds. It’s not rocket science; it’s just cardiology. 

Arguing about five millimeters of mercury of blood pressure is probably less important from the public health perspective than the fact that tens of millions of people in the United States are unaware that they have hypertension, and even those diagnosed are being inadequately treated.

So, let’s all do better as a medical community. Nobody should have untreated hypertension in this day and age. It’s not the 1930s. 
 

Dr Labos, Cardiologist, Kirkland Medical Center, Montreal, Quebec, Canada, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Aerobic exercise shows a linear relationship with weight loss, with 30 minutes of weekly exercise linked to reduced body weight, waist circumference, and body fat in adults who were overweight or had obesity.

METHODOLOGY:

• Researchers conducted a meta-analysis of randomized clinical trials to investigate the association of varying intensities and durations of aerobic exercise with adiposity measures in adults with obesity or who were overweight.
• Overall, 116 randomized clinical trials that spanned across North America, Asia, Europe, Australia, South America, and Africa and involved 6880 adults (mean age, 46 years; 61% women) were included.
• The trials were required to have intervention durations of at least 8 weeks; all trials used supervised aerobic exercise, such as walking or running, while the control groups remained sedentary or continued usual activities.
• The intensity of exercise was defined as: Light (40%-55% maximum heart rate), moderate (55%-70% maximum heart rate), and vigorous (70%-90% maximum heart rate).
• The primary outcomes were body weight changes and adverse events; the secondary outcomes included changes in waist circumference, quality-of-life scores, and reduction in medications like antihypertensives.

TAKEAWAY:

• Every 30 minutes of aerobic exercise per week was associated with a 1.14 lb reduction in body weight (certainty of evidence, moderate).
• Every 30 minutes of aerobic exercise per week was also associated with lower waist circumference (mean difference, −0.56 cm; 95% CI, –0.67 to –0.45), body fat percentage (mean difference, –0.37%; 95% CI, –0.43 to –0.31), and body fat mass (mean difference, –0.20 kg; 95% CI, –0.32 to –0.08), along with reduced visceral and subcutaneous adipose tissue.
• A dose-response meta-analysis revealed that body fat percentage improved most significantly with 150 minutes of aerobic exercise per week, while body weight and waist circumference decreased linearly with increasing duration of aerobic exercise at 300 min/wk at different intensities.
• Adverse events with aerobic exercise were mostly mild or moderate musculoskeletal symptoms.

IN PRACTICE:

“Point-specific estimates for different aerobic exercise duration and intensity can help patients and healthcare professionals select the optimal aerobic exercise duration and intensity according to their weight loss goals,” the authors wrote.

 

SOURCE:

The study was led by Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics in the School of Public Health at the Imperial College London in England. It was published online on December 26, 2024, in JAMA Network Open.

 

LIMITATIONS:

High heterogeneity was present in the data. Only one trial included measures of health-related quality of life, and two studies included measures of medication use. Dietary habits and smoking status of participants were not included in studies, so any potential effects were not risk adjusted for.

 

DISCLOSURES:

No funding sources were reported. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Aerobic exercise shows a linear relationship with weight loss, with 30 minutes of weekly exercise linked to reduced body weight, waist circumference, and body fat in adults who were overweight or had obesity.

METHODOLOGY:

• Researchers conducted a meta-analysis of randomized clinical trials to investigate the association of varying intensities and durations of aerobic exercise with adiposity measures in adults with obesity or who were overweight.
• Overall, 116 randomized clinical trials that spanned across North America, Asia, Europe, Australia, South America, and Africa and involved 6880 adults (mean age, 46 years; 61% women) were included.
• The trials were required to have intervention durations of at least 8 weeks; all trials used supervised aerobic exercise, such as walking or running, while the control groups remained sedentary or continued usual activities.
• The intensity of exercise was defined as: Light (40%-55% maximum heart rate), moderate (55%-70% maximum heart rate), and vigorous (70%-90% maximum heart rate).
• The primary outcomes were body weight changes and adverse events; the secondary outcomes included changes in waist circumference, quality-of-life scores, and reduction in medications like antihypertensives.

TAKEAWAY:

• Every 30 minutes of aerobic exercise per week was associated with a 1.14 lb reduction in body weight (certainty of evidence, moderate).
• Every 30 minutes of aerobic exercise per week was also associated with lower waist circumference (mean difference, −0.56 cm; 95% CI, –0.67 to –0.45), body fat percentage (mean difference, –0.37%; 95% CI, –0.43 to –0.31), and body fat mass (mean difference, –0.20 kg; 95% CI, –0.32 to –0.08), along with reduced visceral and subcutaneous adipose tissue.
• A dose-response meta-analysis revealed that body fat percentage improved most significantly with 150 minutes of aerobic exercise per week, while body weight and waist circumference decreased linearly with increasing duration of aerobic exercise at 300 min/wk at different intensities.
• Adverse events with aerobic exercise were mostly mild or moderate musculoskeletal symptoms.

IN PRACTICE:

“Point-specific estimates for different aerobic exercise duration and intensity can help patients and healthcare professionals select the optimal aerobic exercise duration and intensity according to their weight loss goals,” the authors wrote.

 

SOURCE:

The study was led by Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics in the School of Public Health at the Imperial College London in England. It was published online on December 26, 2024, in JAMA Network Open.

 

LIMITATIONS:

High heterogeneity was present in the data. Only one trial included measures of health-related quality of life, and two studies included measures of medication use. Dietary habits and smoking status of participants were not included in studies, so any potential effects were not risk adjusted for.

 

DISCLOSURES:

No funding sources were reported. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Aerobic exercise shows a linear relationship with weight loss, with 30 minutes of weekly exercise linked to reduced body weight, waist circumference, and body fat in adults who were overweight or had obesity.

METHODOLOGY:

• Researchers conducted a meta-analysis of randomized clinical trials to investigate the association of varying intensities and durations of aerobic exercise with adiposity measures in adults with obesity or who were overweight.
• Overall, 116 randomized clinical trials that spanned across North America, Asia, Europe, Australia, South America, and Africa and involved 6880 adults (mean age, 46 years; 61% women) were included.
• The trials were required to have intervention durations of at least 8 weeks; all trials used supervised aerobic exercise, such as walking or running, while the control groups remained sedentary or continued usual activities.
• The intensity of exercise was defined as: Light (40%-55% maximum heart rate), moderate (55%-70% maximum heart rate), and vigorous (70%-90% maximum heart rate).
• The primary outcomes were body weight changes and adverse events; the secondary outcomes included changes in waist circumference, quality-of-life scores, and reduction in medications like antihypertensives.

TAKEAWAY:

• Every 30 minutes of aerobic exercise per week was associated with a 1.14 lb reduction in body weight (certainty of evidence, moderate).
• Every 30 minutes of aerobic exercise per week was also associated with lower waist circumference (mean difference, −0.56 cm; 95% CI, –0.67 to –0.45), body fat percentage (mean difference, –0.37%; 95% CI, –0.43 to –0.31), and body fat mass (mean difference, –0.20 kg; 95% CI, –0.32 to –0.08), along with reduced visceral and subcutaneous adipose tissue.
• A dose-response meta-analysis revealed that body fat percentage improved most significantly with 150 minutes of aerobic exercise per week, while body weight and waist circumference decreased linearly with increasing duration of aerobic exercise at 300 min/wk at different intensities.
• Adverse events with aerobic exercise were mostly mild or moderate musculoskeletal symptoms.

IN PRACTICE:

“Point-specific estimates for different aerobic exercise duration and intensity can help patients and healthcare professionals select the optimal aerobic exercise duration and intensity according to their weight loss goals,” the authors wrote.

 

SOURCE:

The study was led by Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics in the School of Public Health at the Imperial College London in England. It was published online on December 26, 2024, in JAMA Network Open.

 

LIMITATIONS:

High heterogeneity was present in the data. Only one trial included measures of health-related quality of life, and two studies included measures of medication use. Dietary habits and smoking status of participants were not included in studies, so any potential effects were not risk adjusted for.

 

DISCLOSURES:

No funding sources were reported. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

The scientific report that offers evidence-based guidance for the next iteration of the Dietary Guidelines for Americans has been submitted to federal agencies, and the document — which already has generated controversy because of its emphasis on plant-based foods — is now open for public comment.

The advisory committee that developed the report examined the scientific evidence on specific nutrition and public health topics using data analysis, systematic reviews, and food modeling. 

“We saw something over and over again — when you look at a population level, diets for which the predominant composition was plants performed better when it came to health outcomes,” advisory committee member Cheryl Anderson, PhD, MPH, who is a professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, said in an interview. “There’s a pretty consistent body of literature showing benefits of fruits, vegetables, and legumes and reductions in salt, added sugars, and saturated fats.”

Clinicians should read and comment on the report, said Anderson.

“Commenting sends the right signal that they are interested in what’s needed for nutrition education,” she said. “It will also activate a conversation with the people who are writing the guidelines.”

Instructions for submitting comments online through February 10, 2025, and for participating in the oral comment meeting on January 16, 2025, are posted online.

The Department of Agriculture (USDA) and the Department of Health & Human Services will use the report as a key resource, alongside the public comments and agency input, as they jointly develop the Dietary Guidelines for Americans, 2025-2030.

 

Meat Given a Back Seat

Overall, the advisory committee defined a “healthy dietary pattern” as one that is “higher in vegetables, fruits, legumes (ie, beans, peas, lentils), nuts, whole grains, fish/seafood, and vegetable oils higher in unsaturated fat — and lower in red and processed meats, sugar-sweetened foods and beverages, refined grains, and saturated fat.”

The report emphasizes “plain drinking water” as the primary beverage for people to consume and states that sugar-sweetened beverage consumption should be limited.

It recommends limiting total saturated fat intake to less than 10% of daily calories and replacing it with unsaturated fat, particularly polyunsaturated fats.

Notably, the report advocates increasing the consumption of beans, peas, and lentils and decreasing starchy vegetables (such as potatoes), as well as reducing total protein foods by reducing meat, poultry, and eggs. This recommendation and the report’s broad emphasis on plant-based foods have drawn criticism, mainly from the food industry.

Also likely to be controversial are the recommendations to move beans, peas, and lentils from the vegetable group to the protein group and the proposed reorganization of the order of the protein foods group to list beans, peas, and lentils first, followed by nuts, seeds, and soy products; then seafood; and finally meats, poultry, and eggs.

Gastroenterologists and dietitians should support the emphasis on plant-based protein sources, water for hydration, and the importance of personalized nutrition plans, including culturally diverse and ethnic food options, said Stephanie Gold, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai and a gastroenterologist at Mount Sinai Hospital, both in New York City.

“The newly proposed 2025 Dietary Guidelines are approaching a Mediterranean-style diet by focusing on plant-based protein sources while limiting red meat and saturated fats, as well as added sugar. By including these legumes in the protein category (not only as a starchy vegetable), the proposed guideline recognizes both the health benefits and sustainability of plant-based proteins,” Gold said in an interview.

Although the report recognizes “the potential negative impact and the varying definitions of ultra-processed foods, it does not provide concrete recommendations regarding intake, and perhaps, this could be an area of focus going forward,” she added.

Anderson noted that the science around ultra-processed food is “underdeveloped.” However, the definition of a healthy diet “has never suggested that we have foods that are extremely processed in it.”

“Right now, there’s a lot of interest in ultra-processed foods and what they mean for health, but the science is going to need to catch up with that interest,” Anderson said.

 

What’s Next

The release of the scientific report is part of a five-step process to develop the new guidelines that included input from the public during the report’s development. According to the USDA, the advisory committee received approximately 9900 public comments, more than any other previous committee.

Once the new dietary guidelines are complete, Anderson said, “clinicians have an opportunity to really lean into a science-based framework to talk about overall health concerns and reducing the burden of diet-related illnesses with their patients.”

Meanwhile, they can voice their approval or concerns about the scientific report.

Anderson and Gold reported no relevant conflicts of interest.

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

The scientific report that offers evidence-based guidance for the next iteration of the Dietary Guidelines for Americans has been submitted to federal agencies, and the document — which already has generated controversy because of its emphasis on plant-based foods — is now open for public comment.

The advisory committee that developed the report examined the scientific evidence on specific nutrition and public health topics using data analysis, systematic reviews, and food modeling. 

“We saw something over and over again — when you look at a population level, diets for which the predominant composition was plants performed better when it came to health outcomes,” advisory committee member Cheryl Anderson, PhD, MPH, who is a professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, said in an interview. “There’s a pretty consistent body of literature showing benefits of fruits, vegetables, and legumes and reductions in salt, added sugars, and saturated fats.”

Clinicians should read and comment on the report, said Anderson.

“Commenting sends the right signal that they are interested in what’s needed for nutrition education,” she said. “It will also activate a conversation with the people who are writing the guidelines.”

Instructions for submitting comments online through February 10, 2025, and for participating in the oral comment meeting on January 16, 2025, are posted online.

The Department of Agriculture (USDA) and the Department of Health & Human Services will use the report as a key resource, alongside the public comments and agency input, as they jointly develop the Dietary Guidelines for Americans, 2025-2030.

 

Meat Given a Back Seat

Overall, the advisory committee defined a “healthy dietary pattern” as one that is “higher in vegetables, fruits, legumes (ie, beans, peas, lentils), nuts, whole grains, fish/seafood, and vegetable oils higher in unsaturated fat — and lower in red and processed meats, sugar-sweetened foods and beverages, refined grains, and saturated fat.”

The report emphasizes “plain drinking water” as the primary beverage for people to consume and states that sugar-sweetened beverage consumption should be limited.

It recommends limiting total saturated fat intake to less than 10% of daily calories and replacing it with unsaturated fat, particularly polyunsaturated fats.

Notably, the report advocates increasing the consumption of beans, peas, and lentils and decreasing starchy vegetables (such as potatoes), as well as reducing total protein foods by reducing meat, poultry, and eggs. This recommendation and the report’s broad emphasis on plant-based foods have drawn criticism, mainly from the food industry.

Also likely to be controversial are the recommendations to move beans, peas, and lentils from the vegetable group to the protein group and the proposed reorganization of the order of the protein foods group to list beans, peas, and lentils first, followed by nuts, seeds, and soy products; then seafood; and finally meats, poultry, and eggs.

Gastroenterologists and dietitians should support the emphasis on plant-based protein sources, water for hydration, and the importance of personalized nutrition plans, including culturally diverse and ethnic food options, said Stephanie Gold, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai and a gastroenterologist at Mount Sinai Hospital, both in New York City.

“The newly proposed 2025 Dietary Guidelines are approaching a Mediterranean-style diet by focusing on plant-based protein sources while limiting red meat and saturated fats, as well as added sugar. By including these legumes in the protein category (not only as a starchy vegetable), the proposed guideline recognizes both the health benefits and sustainability of plant-based proteins,” Gold said in an interview.

Although the report recognizes “the potential negative impact and the varying definitions of ultra-processed foods, it does not provide concrete recommendations regarding intake, and perhaps, this could be an area of focus going forward,” she added.

Anderson noted that the science around ultra-processed food is “underdeveloped.” However, the definition of a healthy diet “has never suggested that we have foods that are extremely processed in it.”

“Right now, there’s a lot of interest in ultra-processed foods and what they mean for health, but the science is going to need to catch up with that interest,” Anderson said.

 

What’s Next

The release of the scientific report is part of a five-step process to develop the new guidelines that included input from the public during the report’s development. According to the USDA, the advisory committee received approximately 9900 public comments, more than any other previous committee.

Once the new dietary guidelines are complete, Anderson said, “clinicians have an opportunity to really lean into a science-based framework to talk about overall health concerns and reducing the burden of diet-related illnesses with their patients.”

Meanwhile, they can voice their approval or concerns about the scientific report.

Anderson and Gold reported no relevant conflicts of interest.

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

The scientific report that offers evidence-based guidance for the next iteration of the Dietary Guidelines for Americans has been submitted to federal agencies, and the document — which already has generated controversy because of its emphasis on plant-based foods — is now open for public comment.

The advisory committee that developed the report examined the scientific evidence on specific nutrition and public health topics using data analysis, systematic reviews, and food modeling. 

“We saw something over and over again — when you look at a population level, diets for which the predominant composition was plants performed better when it came to health outcomes,” advisory committee member Cheryl Anderson, PhD, MPH, who is a professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, said in an interview. “There’s a pretty consistent body of literature showing benefits of fruits, vegetables, and legumes and reductions in salt, added sugars, and saturated fats.”

Clinicians should read and comment on the report, said Anderson.

“Commenting sends the right signal that they are interested in what’s needed for nutrition education,” she said. “It will also activate a conversation with the people who are writing the guidelines.”

Instructions for submitting comments online through February 10, 2025, and for participating in the oral comment meeting on January 16, 2025, are posted online.

The Department of Agriculture (USDA) and the Department of Health & Human Services will use the report as a key resource, alongside the public comments and agency input, as they jointly develop the Dietary Guidelines for Americans, 2025-2030.

 

Meat Given a Back Seat

Overall, the advisory committee defined a “healthy dietary pattern” as one that is “higher in vegetables, fruits, legumes (ie, beans, peas, lentils), nuts, whole grains, fish/seafood, and vegetable oils higher in unsaturated fat — and lower in red and processed meats, sugar-sweetened foods and beverages, refined grains, and saturated fat.”

The report emphasizes “plain drinking water” as the primary beverage for people to consume and states that sugar-sweetened beverage consumption should be limited.

It recommends limiting total saturated fat intake to less than 10% of daily calories and replacing it with unsaturated fat, particularly polyunsaturated fats.

Notably, the report advocates increasing the consumption of beans, peas, and lentils and decreasing starchy vegetables (such as potatoes), as well as reducing total protein foods by reducing meat, poultry, and eggs. This recommendation and the report’s broad emphasis on plant-based foods have drawn criticism, mainly from the food industry.

Also likely to be controversial are the recommendations to move beans, peas, and lentils from the vegetable group to the protein group and the proposed reorganization of the order of the protein foods group to list beans, peas, and lentils first, followed by nuts, seeds, and soy products; then seafood; and finally meats, poultry, and eggs.

Gastroenterologists and dietitians should support the emphasis on plant-based protein sources, water for hydration, and the importance of personalized nutrition plans, including culturally diverse and ethnic food options, said Stephanie Gold, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai and a gastroenterologist at Mount Sinai Hospital, both in New York City.

“The newly proposed 2025 Dietary Guidelines are approaching a Mediterranean-style diet by focusing on plant-based protein sources while limiting red meat and saturated fats, as well as added sugar. By including these legumes in the protein category (not only as a starchy vegetable), the proposed guideline recognizes both the health benefits and sustainability of plant-based proteins,” Gold said in an interview.

Although the report recognizes “the potential negative impact and the varying definitions of ultra-processed foods, it does not provide concrete recommendations regarding intake, and perhaps, this could be an area of focus going forward,” she added.

Anderson noted that the science around ultra-processed food is “underdeveloped.” However, the definition of a healthy diet “has never suggested that we have foods that are extremely processed in it.”

“Right now, there’s a lot of interest in ultra-processed foods and what they mean for health, but the science is going to need to catch up with that interest,” Anderson said.

 

What’s Next

The release of the scientific report is part of a five-step process to develop the new guidelines that included input from the public during the report’s development. According to the USDA, the advisory committee received approximately 9900 public comments, more than any other previous committee.

Once the new dietary guidelines are complete, Anderson said, “clinicians have an opportunity to really lean into a science-based framework to talk about overall health concerns and reducing the burden of diet-related illnesses with their patients.”

Meanwhile, they can voice their approval or concerns about the scientific report.

Anderson and Gold reported no relevant conflicts of interest.

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

TOPLINE:

The administration of potassium nitrate (KNO₃) does not improve exercise capacity or quality of life in patients with heart failure with preserved ejection fraction (HFpEF), despite increasing levels of nitric oxide in blood.

METHODOLOGY:

• This multicenter crossover trial, conducted across three centers in the United States, assessed the effect of administering KNO3 on exercise capacity and quality of life.
• It included 84 patients with symptomatic HFpEF (median age, 68 years; 69% women; 76% White) who had a left ventricular ejection fraction over 50% and elevated intracardiac pressures. Participants had obesity (mean body mass index, 36.22), with a high prevalence of hypertension, diabetes, and obstructive sleep apnea.
• Patients were randomly assigned to receive either 6 mmol KNO₃ first (n = 41) or 6 mmol potassium chloride (KCl) first (n = 43) three times daily for 6 weeks, with a 1-week washout period in between.
• At the end of each intervention phase, a test of incremental cardiopulmonary exercise was conducted using a supine cycle ergometer.
• Primary endpoints were the difference in peak oxygen uptake and total work performed during the exercise test; secondary endpoints included quality of life, left ventricular systolic and diastolic function, exercise systemic vasodilatory reserve, and parameters related to pulsatile arterial load.

TAKEAWAY:

• The administration of KNO₃ vs KCl increased the levels of serum metabolites of nitric oxide significantly after 6 weeks (418.44 vs 40.11 μM; P < .001).
• Peak oxygen uptake or the total work performed did not improve significantly with the administration of KNO₃, compared with KCl. Quality of life also did not improve with the administration of KNO₃.
• Mean arterial pressure at peak exercise was significantly lower after the administration of KNO₃ than after KCl (122.5 vs 127.6 mm Hg; P = .04), but the vasodilatory reserve and resting and orthostatic blood pressure did not differ.
• Adverse events were mostly minor, with gastrointestinal issues being the most common side effects reported.

IN PRACTICE:

“In this randomized crossover trial, chronic KNO₃ administration did not improve exercise capacity or quality of life, as compared with KCl among participants with HFpEF,” the authors of the study wrote.

SOURCE:

The study was led by Payman Zamani, MD, MTR, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. It was published online on December 18, 2024, in JAMA Cardiology.

LIMITATIONS:

The potential activation of compensatory mechanisms by the chronic inorganic nitrate administration may have neutralized the short-term benefits. Various abnormalities in oxygen transport may be present simultaneously in patients with HFpEF, suggesting a combination of interventions may be required to improve exercise capacity.

DISCLOSURES:

This trial was supported by the National Heart, Lung, and Blood Institute. The study was supported by the National Center for Advancing Translational Sciences and National Institutes of Health. Some authors reported receiving grants, personal fees, and consulting fees and having patents from various pharmaceutical and medical device companies and institutes. One author reported having full-time employment with a healthcare company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The administration of potassium nitrate (KNO₃) does not improve exercise capacity or quality of life in patients with heart failure with preserved ejection fraction (HFpEF), despite increasing levels of nitric oxide in blood.

METHODOLOGY:

• This multicenter crossover trial, conducted across three centers in the United States, assessed the effect of administering KNO3 on exercise capacity and quality of life.
• It included 84 patients with symptomatic HFpEF (median age, 68 years; 69% women; 76% White) who had a left ventricular ejection fraction over 50% and elevated intracardiac pressures. Participants had obesity (mean body mass index, 36.22), with a high prevalence of hypertension, diabetes, and obstructive sleep apnea.
• Patients were randomly assigned to receive either 6 mmol KNO₃ first (n = 41) or 6 mmol potassium chloride (KCl) first (n = 43) three times daily for 6 weeks, with a 1-week washout period in between.
• At the end of each intervention phase, a test of incremental cardiopulmonary exercise was conducted using a supine cycle ergometer.
• Primary endpoints were the difference in peak oxygen uptake and total work performed during the exercise test; secondary endpoints included quality of life, left ventricular systolic and diastolic function, exercise systemic vasodilatory reserve, and parameters related to pulsatile arterial load.

TAKEAWAY:

• The administration of KNO₃ vs KCl increased the levels of serum metabolites of nitric oxide significantly after 6 weeks (418.44 vs 40.11 μM; P < .001).
• Peak oxygen uptake or the total work performed did not improve significantly with the administration of KNO₃, compared with KCl. Quality of life also did not improve with the administration of KNO₃.
• Mean arterial pressure at peak exercise was significantly lower after the administration of KNO₃ than after KCl (122.5 vs 127.6 mm Hg; P = .04), but the vasodilatory reserve and resting and orthostatic blood pressure did not differ.
• Adverse events were mostly minor, with gastrointestinal issues being the most common side effects reported.

IN PRACTICE:

“In this randomized crossover trial, chronic KNO₃ administration did not improve exercise capacity or quality of life, as compared with KCl among participants with HFpEF,” the authors of the study wrote.

SOURCE:

The study was led by Payman Zamani, MD, MTR, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. It was published online on December 18, 2024, in JAMA Cardiology.

LIMITATIONS:

The potential activation of compensatory mechanisms by the chronic inorganic nitrate administration may have neutralized the short-term benefits. Various abnormalities in oxygen transport may be present simultaneously in patients with HFpEF, suggesting a combination of interventions may be required to improve exercise capacity.

DISCLOSURES:

This trial was supported by the National Heart, Lung, and Blood Institute. The study was supported by the National Center for Advancing Translational Sciences and National Institutes of Health. Some authors reported receiving grants, personal fees, and consulting fees and having patents from various pharmaceutical and medical device companies and institutes. One author reported having full-time employment with a healthcare company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The administration of potassium nitrate (KNO₃) does not improve exercise capacity or quality of life in patients with heart failure with preserved ejection fraction (HFpEF), despite increasing levels of nitric oxide in blood.

METHODOLOGY:

• This multicenter crossover trial, conducted across three centers in the United States, assessed the effect of administering KNO3 on exercise capacity and quality of life.
• It included 84 patients with symptomatic HFpEF (median age, 68 years; 69% women; 76% White) who had a left ventricular ejection fraction over 50% and elevated intracardiac pressures. Participants had obesity (mean body mass index, 36.22), with a high prevalence of hypertension, diabetes, and obstructive sleep apnea.
• Patients were randomly assigned to receive either 6 mmol KNO₃ first (n = 41) or 6 mmol potassium chloride (KCl) first (n = 43) three times daily for 6 weeks, with a 1-week washout period in between.
• At the end of each intervention phase, a test of incremental cardiopulmonary exercise was conducted using a supine cycle ergometer.
• Primary endpoints were the difference in peak oxygen uptake and total work performed during the exercise test; secondary endpoints included quality of life, left ventricular systolic and diastolic function, exercise systemic vasodilatory reserve, and parameters related to pulsatile arterial load.

TAKEAWAY:

• The administration of KNO₃ vs KCl increased the levels of serum metabolites of nitric oxide significantly after 6 weeks (418.44 vs 40.11 μM; P < .001).
• Peak oxygen uptake or the total work performed did not improve significantly with the administration of KNO₃, compared with KCl. Quality of life also did not improve with the administration of KNO₃.
• Mean arterial pressure at peak exercise was significantly lower after the administration of KNO₃ than after KCl (122.5 vs 127.6 mm Hg; P = .04), but the vasodilatory reserve and resting and orthostatic blood pressure did not differ.
• Adverse events were mostly minor, with gastrointestinal issues being the most common side effects reported.

IN PRACTICE:

“In this randomized crossover trial, chronic KNO₃ administration did not improve exercise capacity or quality of life, as compared with KCl among participants with HFpEF,” the authors of the study wrote.

SOURCE:

The study was led by Payman Zamani, MD, MTR, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. It was published online on December 18, 2024, in JAMA Cardiology.

LIMITATIONS:

The potential activation of compensatory mechanisms by the chronic inorganic nitrate administration may have neutralized the short-term benefits. Various abnormalities in oxygen transport may be present simultaneously in patients with HFpEF, suggesting a combination of interventions may be required to improve exercise capacity.

DISCLOSURES:

This trial was supported by the National Heart, Lung, and Blood Institute. The study was supported by the National Center for Advancing Translational Sciences and National Institutes of Health. Some authors reported receiving grants, personal fees, and consulting fees and having patents from various pharmaceutical and medical device companies and institutes. One author reported having full-time employment with a healthcare company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in The British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

 

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

 

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds in England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO₂ max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO₂ max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

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

Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in The British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

 

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

 

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds in England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO₂ max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO₂ max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

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

Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in The British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

 

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

 

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds in England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO₂ max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO₂ max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

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