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Dr. Leandro Slipczuk discusses his recently published research which examined how exercise volume impacts sex-specific atherosclerotic risk.

High‐volume endurance exercise increases risk for coronary artery calcification and plaque burden among males but not females, according to a meta‑analysis published in JACC: Advances. Yet, moderate-volume exercise lowers plaque volumes in both sexes compared with nonathletes, indicating sex-specific relationships between exercise dose and subclinical atherosclerosis.

Physician’s Weekly (PW) discussed the study findings with corresponding author Leandro Slipczuk, MD, PhD, director of Advanced Cardiac Imaging and the Cardiovascular Atherosclerosis and Lipid Disorder Center at Montefiore Einstein.

PW: What inspired this research?

Dr. Slipczuk: My main area of research is the influence and relationship between risk factors and atherosclerosis, determining how to increase our yield of individuals at real risk but not represented by risk factors. I’m also very interested in exercise—it’s an essential part of prevention—but some research has suggested that, paradoxically, certain exercises being recommended for patients could have a negative effect, causing more plaque in certain patients. This prompted us to conduct a meta-analysis of cardiovascular studies that compared the impact of a high volume of exercise, exceeding 3,000 METS (metabolic equivalents of task) per week, to that of no exercise.

Does that threshold describe elite athletes or normal gym‑goers?

I avoid the term normal because it’s normal for humans to exercise, and exercise is a free, preventive therapy we actively recommend. Guidelines call for 150 minutes of moderate or 75 minutes of vigorous activity weekly; 3,000 MET‑minutes is well above that, but reachable by anyone running hard for an hour 3 to 4 days a week or jogging 5 to 6. In other words, we’re talking about people who exercise regularly with exertion for a good amount of time. Of course, within that definition, levels of exercise can vary greatly, which is a limitation of this meta‑analysis.

How was the study executed?

We examined nine observational studies involving a total of 61,150 participants that assessed the impact of different exercise volumes on subclinical atherosclerosis, measured by CAC [coronary artery calcification] scoring or CCTA [CT angiography]. Subclinical atherosclerosis means that plaque formed by cholesterol is in the arteries of people who aren’t aware it’s there, so they’re asymptomatic but at risk. The calcium score measures calcified plaque, which is traditionally more stable and lower risk, while the CCTA allows you to see both the calcified plaque and the noncalcified plaque, which is higher risk.

We split the data by sex because risk factors can affect male and female individuals differently. 

What did you discover?

Male individuals who exercised more than 3,000 MET‑minutes per week had significantly higher calcium scores than males who didn’t exercise. We did not find this result in females. In CCTA analyses, males who exercised significantly had larger volumes of calcified lesions, while females who exercised moderately had slightly lower plaque volumes. 

Are you concerned that the findings may be misinterpreted?

I definitely do not want this study to be interpreted as, “I shouldn’t exercise” or “I should exercise less.” It’s very important to understand that while our study found that men performing more than 3,000 MET‑minutes of weekly exercise exhibit higher volumes of calcified plaque, that does not mean they’re at high risk of having a heart attack—a point some media misreported. There could be many reasons why these men have more plaque—diet, medications, smoking, other risk factors—and self‑reported exercise capacities and volumes are susceptible to recall bias. Although having plaque is worse than having no plaque, studies have shown that people who exercise regularly have fewer (cardiac) events and lower mortality than those who don’t exercise. Our point is that people who exercise like this may have more plaque. That means we need to pay closer attention to all the risk factors and determine how we can effectively control them. 

Do conventional cardiovascular risk scores underestimate atherosclerotic risk among men who follow high-volume exercise routines?

Cardiovascular risk assessments may be underestimating risk in both younger and more fit individuals, but how much of these risks extrapolate to overall risk in athletes? We know their overall risk is lower compared to those who do not exercise, but it gets tricky because the level of risk is dependent on the amount of calcium they have. That’s why we’re trying to view plaque in terms of stages of disease: more plaque means a higher stage of disease, warranting intensification of therapies.

Which preventive therapies do you suggest?

Prevention starts with information. I encourage physicians to consider calcium scoring for risk stratification in those without a history of coronary disease. If we know there is underlying plaque, we can measure cholesterol, treat with statins or multiple other medications, control blood pressure, and modify diet. 

Which resources do you recommend for clinicians who wish to learn more about subclinical atherosclerosis?

Here at Montefiore, we’ve launched our free MonteHeart Lectures channel on YouTube. It features lectures from top experts worldwide and is available to everyone. Reliable, professional websites I recommend include the American Society for Preventive Cardiology, the American Heart Association, the American College of Cardiology, and the National Lipid Association. 

What are your plans for future research?

We want to quantify non‑calcified, high‑risk plaque using contrast CCTA and advanced software that measures plaque volume and perivascular inflammation. We need this information for athletes, and we need more information when correcting for risk factors. There is still much work to be done to better tailor therapies to these individuals.