Exercise Volume vs Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes

Coronary atherosclerosis in athletes: is exercise volume or intensity the culprit?

Physical activity and athletic participation have long been associated with longevity and reduced atherosclerotic cardiovascular disease events, but recent studies have demonstrated that endurance athletes have more coronary artery calcification (CAC) and atherosclerotic plaque than comparison subjects.¹ The Measuring Athletes Risk of Cardiovascular events, or “MARC-1,” study used coronary computed tomography angiography to examine coronary anatomy in healthy, middle-aged (55±7 years) athletes in the Netherlands.² Athletes with the highest lifelong exercise levels had the highest CAC scores and the highest prevalence of atherosclerotic plaques. MARC-1 also found that the most vigorous exercise was associated with both CAC and plaque prevalence.

The recently published MARC-2 study examined coronary disease progression in 289 of the original 318 MARC-1 athletes to determine whether exercise amount or intensity contributed more to disease progression.³ The amount or volume of exercise was measured as metabolic equivalents of task in hours per week. Exercise intensity was classified (in metabolic equivalents of task) as moderate (3–6 h/wk), vigorous (6–9 h/wk), or very vigorous (>9 h/wk). Both CAC prevalence and score increased over the 6.3±0.5 years of follow-up. Disease progression was not associated with the volume of exercise but was associated with exercise intensity. Vigorous exercise was associated with a smaller increase in CAC. In contrast, very vigorous exercise was associated with both an increase in CAC and mixed plaques, which are thought to be the type of plaque most vulnerable to rupture and erosion.

This apparently paradoxical relationship between lifelong endurance exercise and increased coronary atherosclerosis is an evolving story. Consensus is building that very vigorous exercise is the primary provocateur,¹ but it is too early to make exercise recommendations to our patients based on available data. Perhaps the most important clinical message, given the increased frequency of CAC measurement, is to be aware that increased CAC is more common in lifelong athletes but, so far, without firm evidence that this is deleterious. Clinical management is also unclear. I contributed to both MARC studies, so I am frequently referred athletes with high CAC scores. My approach is to reassure patients that atherosclerosis in athletes can occur, including in Clarence DeMar — the seven-time winner of the Boston Marathon⁴ — without apparent problems but also to treat the athletes’ atherosclerotic cardiovascular disease risk factors aggressively. To paraphrase the WWII rallying cry, “Praise the Lord and pass the ammunition," reassure the patient, but treat the dickens out of his risk factors.

References

1. Aengevaeren VL, Mosterd A, Sharma S, et al. Exercise and Coronary Atherosclerosis: Observations, Explanations, Relevance, and Clinical Management. 2020;141(16):1338-1350. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044467
2. Aengevaeren VL, Mosterd A, Braber TL, et al. Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes. 2017;136(2):138-148. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.027834
3. Aengevaeren VL , Mosterd A, Bakker EA, et al. Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study. Circulation. 2023 Jan 4. doi: 10.1161/CIRCULATIONAHA.122.061173. Online ahead of print. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061173
4. Currens JH, White PD. Half a Century of Running — Clinical, Physiologic and Autopsy Findings in the Case of Clarence DeMar (Mr. Marathon). N Engl J Med. 1961;265:988-993. https://www.nejm.org/doi/full/10.1056/NEJM196111162652006

This was a longitudinal study examining the relationship between exercise volume versus intensity and coronary atherosclerosis formation. The authors noted that exercise volume was not associated with changes in coronary artery calcification or plaques. However, very vigorous exercise intensity was associated with the progression of coronary artery calcification in this 6-year study involving 289 patients.

It is unexpected that athletes who engaged in very vigorous–intensity exercise had increased coronary artery calcium scores. Coronary artery calcium score and atherosclerotic plaques are strongly associated with increased cardiovascular events in the general population. However, studies also show that life expectancy is superior in physically active athletic populations compared with the general population. The authors speculate that athletes may have coronary adaptations to exercise and lower-risk plaque morphology, which may account for this population's improved longevity.

Unfortunately, the study did not offer exercise recommendations for either general or athletic populations. Despite worsening coronary atherosclerotic plaques with very vigorous exercise intensity, established studies overwhelmingly support a physically active lifestyle, which leads to improved mortality and morbidity outcomes. The study did not arrive at the following conclusion, which is to question the validity of coronary artery plaque formation in athletes as a reliable marker for cardiovascular risk. I would welcome prospective studies for additional insight.