Higher Physical Activity Linked With CAC Progression

Physical activity may be linked with progression of coronary artery calcium (CAC) regardless of baseline levels, according to new data.

An established predictor of cardiovascular events, even in young people, CAC scores typically track with future risk, with higher scores typically going hand in hand with poor diet, smoking, and physical inactivity. However, the paradox of otherwise healthy athletes—and especially high-volume or endurance athletes—being more likely to have higher CAC scores has been shown before.

“The results are counterintuitive, but they did not surprise us, as the increase in coronary calcium scores may reflect stabilization of coronary plaques,” study co-author Eliseo Guallar, MD, DrPH (Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD), told TCTMD in an email. “A similar phenomenon is also observed after the use of statins.”

While an increase in CAC scores among people who exercise may seem alarming, “this is not necessarily bad news,” he continued. “This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes.”

Commenting on the findings for TCTMD, Matthew Martinez, MD (Morristown Medical Center, NJ), said they emphasize that for all patients, “exercise is not enough” and other standard risk factors still apply.

“You can't smoke and have diabetes and run and think that you are without risk for adverse events,” he said. “When you check a calcium score, zero is the goal, but if the calcium score is elevated, it's an opportunity to think about what you're doing in terms of traditional risk factors, what your exercise regimen looks like, and whether or not you're taking a statin.”

Physical Activity and Increased CAC

For the study, led by Ki-Chul Sung, (Sungkyunkwan University School of Medicine, Seoul, Korea), and published online ahead of print in Heart, the researchers included over 25,000 healthy Korean adults older than 30 (mean age 42 years). All had two or more CAC score measurements (median interval 3.0 years) between March 2011 and December 2017 and had completed the International Physical Activity Questionnaire Short Form assessment (IPAQ-SF).

Overall, 46.8% of participants said they were inactive, 38.0% said they were moderately active, and 15.2% reported being at the level of health-enhancing physically active (HEPA), with corresponding average baseline CAC scores for these groups of 9.45, 10.20, and 12.04. Higher physical activity was more likely in participants who were older, not current smokers, and had healthier lipid levels and higher rates of hypertension and CAC. Notably, however, those with greater than zero CAC at baseline were more likely to be male and current smokers, and had higher levels of traditional cardiovascular risk factors.

Compared with inactive participants, those who were moderately active and those in the HEPA group had an adjusted 5-year average increase in CAC of 3.20 and 8.16, respectively. These increases were seen regardless of baseline CAC score, although with minimal increases in patients with zero CAC at baseline (0.17 and 0.32) and much larger ones in those with higher-than-zero CAC (7.70 and 15.05) at baseline.

Among participants with zero CAC at baseline, multivariable analyses showed greater risks for CAC progression among those who were moderately active (HR 1.04; 95% CI 0.94-1.15) and HEPA (HR 1.21; 95% CI 1.05-1.38) compared with those who were inactive.

Subgroup analyses based on age and sex confirmed the results.

“Our findings should not be interpreted as a harmful effect of physical activity, but, rather, need to be taken into account when evaluating the progression of CAC in patients who exercise to reduce cardiovascular risk,” the authors write. “The cardiovascular benefits of physical activity are unquestionable.”

As for why physical activity may increase the progression of CAC, Sung and colleagues suggest that “potential pathways include mechanical stress and vessel wall injury of coronary arteries, physiological responses during exercise, such as increased blood pressure, increased parathyroid hormone levels, and changes in coronary hemodynamics and inflammation. In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity.”

Importantly, they write, physical activity may also up CAC “without increasing CVD risk,” citing previous research showing that higher-density plaques often seen in athletes are associated with lower risk compared with less-dense ones.

“However, considering the undeniable protective effect of physical activity on 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,” they write. Because the study didn’t exclusively include participants with “extreme levels” of physical activity, it may be more applicable to a general population than prior research, Sung and colleagues add.

What About Clinical Outcomes?

In an accompanying editorial, Gaurav Gulsin, MBBS, and Alastair James Moss, MBBS, PhD (both University of Leicester, England), say the research “fuels a wider discussion of some of the key limitations” associated with using CAC to follow CAD progression.

Baseline CAC levels are the first key to how disease may evolve, Gulsin and Moss write. A CAC score of less than 100 in an asymptomatic 40-year-old is considered “a high burden of disease” and would be expected to increase over 5 years, but a CAC score of zero “would rarely change over the same time frame, leading some investigators to label this as a ‘warranty period’ conferring coronary vascular stability,” they explain. So progression in the former category “is almost inevitable [and] appears to be only marginally influenced by the control of traditional risk factors.”

They also point out that CAC progression does not necessarily equal the same rate of total plaque progression, a point also made by Guallar. “By ‘walling off ’ necrotic cores, calcification may indicate a transition towards a more-stable metabolic phenotype,” the editorialists observe.

Ultimately, the results support the continued use of CAC scoring to assess CAD, although this process can be complex, they conclude. “While proponents 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.”

Martinez agreed. “I think it's an effective tool for identifying individuals with atherosclerosis, especially those that are asymptomatic,” he said. “And we know that if you check a calcium score and it's a zero score, that has impact on whether or not they benefit for a statin. We can't just give statins to everybody. That exercise prescription should still be the first thing we prescribe, and that calcium scoring helps identify those that may be at a higher risk despite exercise.”

He cautioned against applying the results from the HEPA group too generally, as the 30.5% rate of current smokers seemed “exceedingly high.” Additionally, he said, “their BMIs were controlled but their level of diabetes was 7.8%—also higher than I would have anticipated—and their overall total cholesterol and their LDL values were higher than expected, which leads me to believe that physical activity in this group was actually prescribed to them or maybe [they were] scared straight [due to] their existing cardiovascular risk factors.”

The study doesn’t yet answer the question of whether increases in CAC in those who exercise is a causal relationship, an association, or something else entirely, Martinez said. But what is clear is that “just because you exercise doesn't mean you're bulletproof.”

He said he would like to see more research looking at CAC and clinical outcomes, especially with regards to progression in those with baseline scores of zero and no traditional risk factors.

Likewise, Guallar said, “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”