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Physical Activity May Paradoxically Hasten Build-up of Cardiovascular Risk Factor

Physical activity may paradoxically hasten the build-up of calcium deposits in the coronary arteries, the amount of which—measured as the coronary artery calcium (CAC) score—is traditionally used to assess future cardiovascular disease risk, according to the results of a newly published analysis of study data by scientists at the University School of Medicine, Seoul. However, the researchers stressed, findings from this observational study don’t outweigh the numerous health benefits of exercise.

Ki-Chul Sung, MD, PhD, at the division of cardiology, department of medicine, and colleagues, reported on the findings from their study, in Heart, in a paper titled, “Physical activity and progression of coronary artery calcification.”

Regular physical activity is associated with a dose-dependent reduction in the risk of obesity, diabetes, heart attack/stroke, and death, among other things, the authors reported. Guidelines emphasize the central role of physical activity in promoting cardiovascular health and maintaining a healthy lifestyle, and adults are recommended to do at least 150–300 minutes per week of moderate-intensity exercise, or 75–150 minutes per week of vigorous-intensity aerobic activity.

The CAC score is used to guide treatment to ward off a heart attack or stroke. Statins are indicated for most people with a CAC score of 100 or above. And while physical activity does improve a wide range of cardiovascular and metabolic biomarkers, the authors also pointed out that high levels of physical activity may be associated with a higher risk of coronary artery calcification. Prior studies have, for example, found that endurance athletes are more likely to have a comparatively high CAC score than their sedentary peers. “It is still unclear if the higher CAC scores associated with high levels of physical activity are restricted to very high levels of activity, and how current levels of physical activity affect future CAC scores,” the researchers noted.

In a bid to explore this further, the researchers studied healthy adults who underwent regular comprehensive check-ups at two major health centers in Seoul and Suwon, South Korea, between March 2011 and December 2017, as part of the Kangbuk Samsung Health Study. At each health check, participants filled out a questionnaire, which included questions on medical and family history, lifestyle, and educational attainment. Weight (BMI), blood pressure, and blood fats were also assessed.

Physical activity was formally categorized at the first check-up as either inactive, moderately active, or “health-enhancing” (intensely) physically active, using a validated questionnaire. Scans tracked the development and/or progression of coronary artery calcification, which was then scored (CAC score) over an average period of three years.

The final analysis included 25,485 people (22,741 men and 2744 women), aged at least 30, and with at least two CAC scores. The results showed that 47% (11,920 individuals), 38% (9683), and 15% (3882) were, respectively, inactive, moderately active, and intensely physically active—equivalent to running 6.5 km/day.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, higher blood pressure, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification emerged over time, irrespective of CAC scores at the start of the monitoring period. The estimated adjusted average CAC scores in all three groups at the start of the monitoring period were 9.45, 10.20, and 12.04, respectively.

Higher physical activity was in addition associated with faster progression of CAC scores both in those who had no calcium deposits at the start of the monitoring period, and in those who already had a CAC score. Compared with participants who were inactive, the estimated adjusted five-year average increases in CAC scores for moderately and intensely active participants were 3.20 and 8.16, respectively, even after accounting for potentially influential factors, including BMI, blood pressure, and blood fats. “In this large prospective study of apparently healthy men and women, physical activity was associated with a higher prevalence of CAC at baseline and with a faster progression of CAC over follow-up,” the authors wrote. “The association was graded across categories of increased physical activity, and it was observed both in participants free of CAC at baseline and in those with prevalent CAC.”

So while the results showed that people who are very physically active seem to have high levels of calcium deposits in their coronary arteries, despite the important health benefits of exercise, it’s not clear if exercise may itself be associated with calcification (artery hardening). The reported study was also an observational study, and as such, can’t establish cause. The researchers also acknowledged several study limitations, including the absence of an objective assessment of physical activity, and lack of any data on incident heart attacks/stroke or on CAC density or volume. And as they concluded, “Although the implications of a positive association between physical activity and CAC in terms of cardiovascular events need to be established in future studies, our findings do not question the well-established cardiovascular benefits of physical activity … considering the undeniable protective effect of physical activity on [cardiovascular disease] (CVD), the positive relationship between physical activity with CAC progression should be interpreted with caution as the complex interplay between physical activity, CAC progression, and subsequent CVD risk remains largely unknown.”

Physical activity may increase coronary atherosclerosis (artery narrowing) through mechanical stress and vessel wall injury and through the physiological responses it prompts, such as increases in blood pressure and parathyroid hormone, the team explained. Physical activity may also modify the effect of diet, vitamins, and minerals. “The second possibility is that physical activity may increase CAC scores without increasing [cardiovascular disease] risk,” the investigators wrote. Standard CAC scores are calculated as a combination of calcium density and the volume of plaque burden. But, as the team noted, “Higher calcium density, which suggests more stable, calcified plaque, produces a higher CAC score, however, it is associated with lower CVD risk.”

And while the cardiovascular benefits of physical activity are unquestionable, the team noted, reiterating national guidelines, “patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization, and calcification.”

In a linked editorial, Gaurav Gulsin, at the University of British Columbia and St. Paul’s Hospital, Vancouver, and Alastair James Moss, PhD, lecturer at the department of cardiovascular science, University of Leicester, posed the question, “Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?”

The reported study, they pointed out, highlights the complexity of interpreting CAC scores in patients who have upped their physical activity or started taking statins—also associated with higher scores. And while they noted that proponents of using CAC scores “ … would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients.”

In a linked podcast, Moss explained that non-calcified plaque, which is more unstable and more likely to rupture, may be more important and should be scored to assess a person’s future risk of a heart attack or stroke. “It may be the target we need to look for is non-calcified plaque rather than calcified plaque,” he suggested. This wasn’t visible on the scans used in this study. “Increasing rates of coronary artery calcification is a phenomenon that is observed both in response to effective treatment like statin therapy and exercise. But it shouldn’t necessarily be regarded that serial imaging with calcium scans is the best way to accurately assess [cardiovascular disease] risk in these individuals … “Clearly, exercise is one of the best ways of trying to control cardiovascular risk in [people without symptoms].”

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