Physical Activity and the Progression of Coronary Artery Calcification

The ability to measure coronary artery calcification (CAC) by non-invasive computed tomography imaging has led to numerous advances in our ability to detect and manage subclinical atherosclerosis. CAC assessment rightly occupies a prominent role in clinical practice guidelines based on its ability to enhance risk stratification and corollary preventative interventions among people at intermediate risk for acute coronary syndromes. However, the CAC story is not completely straight forward.

It has been established, beyond a shred of doubt, that routine physical activity and high cardiorespiratory fitness independently and synergistically confer a mortality benefit and improve a myriad of tangible health outcomes. Yet, recent studies of highly active, very fit people have generated some surprising twists in our understanding of CAC. German men who run marathons, a group often thought to represent the paradigm of health, have been shown to harbor more CAC than age- and Framingham Risk Factor Score–matched controls.¹ Similarly, a cohort of risk factor–free British cyclists and runners were found to have twice the coronary plaque volume, almost exclusively accounted for by calcific plaque, than normally active controls.² Finally, an analysis of middle-aged Dutch men demonstrated a direct dose-response relationship between CAC and lifelong exercise exposure.³ These important cross-sectional studies are now accompanied by intriguing longitudinal data from the Kangbuk Samsung Health Study.

Among 25,485 Korean people (89% men; age = 42± 6 years) with baseline CAC scores, those who engaged in health-enhancing physical activity—a term defined rigorously in the paper, essentially, the level of exercise needed to meet contemporary physical activity guidelines—experienced a significantly greater increase in CAC after a median follow-up of 3 years compared with inactive people. Importantly, differences in CAC progression remained statistically significant after adjustment for all traditional atherosclerotic risk factors. The authors propose a positive, graded association between physical activity and the prevalence and progression of CAC.

This important paper reminds us that there are two converging lines of evidence that seem challenging to reconcile. First, the presence and magnitude of CAC is powerfully prognostic for incident coronary events among sedentary people. Second, CAC is present at both a higher prevalence and greater magnitude among highly active people than can be explained by conventional drivers of atherosclerosis. A return to basic mechanistic biology proves useful with this enigma. Simplistically speaking, CAC accumulates in the arterial walls during the adaptive process of recovery from different types of insults including lipid accumulation, inflammatory cell activation, and/or mechanical stress. Although confirmatory basic science needs to be done, it is possible if not probable that “athletic CAC” represents an adaptive response to the mechanical coronary stresses of exercise which may in turn stabilize and protect vulnerable arterial segments. If so, its clinical implications may be very different than those attributable “non-athletic” CAC. In practice, CAC may accumulate through numerous concomitant mechanistic pathways, and we need clinical tools to differentiate the good from the bad. In addition, we eagerly await definitive prospective outcomes data among the fittest and the most active who people who tend to harbor very high levels of CAC but also live long and live well.

The final take-home message is that exercise is a form of stress that elicits numerous health-promoting adaptive responses. Although we cannot yet definitively add “athletic CAC” to this list, it looks to be a promising candidate. At the very least, we should pause to consider the possibility that not all CAC is created equal.

References

1. Mohlenkamp S, Lehmann N, Breuckmann F, et al. Running: the risk of coronary events : Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J. 2008;29(15):1903-1910. https://academic.oup.com/eurheartj/article/29/15/1903/509365
2. Merghani A, Maestrini V, Rosmini S, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile. Circulation. 2017;136(2):126-137. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.116.026964
3. Aengevaeren VL, Mosterd A, Braber T, et al. The relationship between lifelong exercise volume and coronary atherosclerosis in athletes. Circulation. 2017;136(2):138-148. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.027834