Exercise recommendations in athletes with coronary artery calcification

Coronary artery calcification (CAC) is a strong marker of coronary atherosclerosis. CAC scoring via computed tomography has emerged as a powerful diagnostic tool to assess for subclinical coronary artery disease and is recommended by current guidelines as an adjunct investigation to inform individual patient management decisions for cardiovascular disease (CVD) prevention.1 CAC scoring establishes the ‘burden’ or quantity of coronary atherosclerosis, and a significant association exists between the amount of CAC and the risk of future CVD events.2 CAC also predicts atherosclerotic CVD risk independent of standard risk factors and regardless of age, sex or race/ethnicity.3 Within the sports medicine and cardiology communities, CAC scoring is emerging as a diagnostic tool for evaluating master athletes for cardiovascular risk, and those with abnormal findings on exercise testing or with symptoms.4 CAC scoring goes beyond traditional screening tools used in younger athletes primarily intended to detect structural abnormalities5 and aims to directly evaluate coronary atherosclerosis, which is the leading cause of sudden cardiac death in older athletes.6 However, CAC scoring is not without its challenges in the adult athletic population. Studies demonstrate that some endurance athletes have higher CAC scores than age matched controls.7,8 This observation, combined with the lack of outcomes data in asymptomatic highly active individuals with CAC raise questions regarding the best management strategy for athletes with elevated CAC. Recent studies investigating the association of mortality with high levels of physical activity and concurrent CAC have advanced our understanding of how to approach treatment and exercise recommendations in this subgroup.9 Analyses of coronary artery plaque composition in athletes show a more stable, less inflamed plaque phenotype compared with their sedentary counterparts.4,10 This renders coronary artery plaque in athletes less prone to acute destabilization and the associated clinical sequelae ultimately leading to acute myocardial infarction. Increased plaque stability in athletes thus provides some biological plausibility for the observation that athletes have a lower risk of cardiovascular death than the general population.11 Higher levels of physical activity, and in particular cardiorespiratory fitness, are inversely related to all-cause and cardiovascular mortality per se.9,12,13 Adding to prior data from Radford et al., who demonstrated that greater cardiorespiratory fitness was associated with lower CVD events at any age and level of CAC (for each additional metabolic equivalent of task of fitness, there was an 11% lower risk),12 recently published data from Defina and colleagues examined the association of CAC and mortality risk across different activity levels. They demonstrated in a large cohort of 21,758 healthy male participants without clinical CVD that higher levels of physical activity were associated with a lower risk of mortality at any given level of CAC.9 Conceptually, calcified plaques, a plaque phenotype often observed in athletes, are stable, less prone to rupture, and have a lower risk for the acute thrombotic complications of atherosclerosis. Thus, calcific plaques in lifelong endurance athletes may protect from acute myocardial infarction, however, the same stable calcified plaques may also cause sufficient coronary stenosis at risk for demand ischaemia (mismatch between oxygen supply and demand) to produce myocardial scarring and fatal arrhythmias in some athletes.7 Demand ischaemia, rather than acute plaque rupture or thrombus formation, was found to be the primary cause of sudden cardiac arrest in older marathon runners.14 Thus, limiting plaque progression and/or improving plaque stability is likely important for all athletes with CAC. The presence of CAC in an athlete deserves a thoughtful cardiovascular risk assessment. Conventional risk factors such as hypertension, dyslipidaemia, hyperglycaemia and/or antecedent hyperinsulinaemia and exposure to cigarette smoke should be carefully managed. Prevention of CVD must begin with control of risk factors at an early age. Exposure to risk factors such as hypertension at a young age increases the cumulative lifetime exposure and may result in premature atherosclerotic plaque formation and earlier end-organ damage.15 Non-traditional determinants of cardiometabolic health must also be addressed. While athletes often maintain a lean physique due to high caloric expenditure, they commonly engage in unhealthy dietary patterns rich in refined carbohydrates and sugars.4 Noteworthy, diet quality impacts on numerous pathways relevant to cardiometabolic health such as adipose tissue distribution, phenotype and secretome.16 Therefore, unhealthy dietary habits cannot fully be compensated by just exercising more and/or maintaining a normal body weight/body mass index. Recommendations in athletes with CAC should thus promote healthy lifestyle choices including dietary patterns low in sugar, low in refined starches and no trans-fatty acids and high in whole foods from animal and plant sources, restorative sleep patterns, and stress management. Chronic exposure to high-risk lifestyle factors such as a poor quality diet, sleep deprivation, psychosocial stress and environmental stressors such as exposure to cigarette smoke, air pollution and noise can facilitate a pro-inflammatory milieu conducive for high-risk atherosclerosis, while low-risk lifestyle factors favourably impact plaque vulnerability by fostering an anti-atherogenic environment.16 The absolute CAC score correlates with the risk of CVD events in the general population: minimal risk < 10; mild risk < 100; moderate risk 100–399; and high risk ≥ 400.17 A zero CAC score denotes a very low risk profile, independent of traditional risk factors.1 In a longitudinal study of young adults, any measureable CAC at baseline was associated with a five-fold increase in fatal and non-fatal CVD events compared with no CAC.18 Lipid lowering pharmacotherapy deserves careful consideration, especially in endurance athletes who have higher levels of CAC and in whom potential myopathic side effects from statin medications may be less tolerable. Current guidelines suggest to consider initiating statin therapy to slow or reverse atheroma progression for a CAC score >100 or an estimated 10-year CVD risk >10%.1 In a large scale cohort of 13,644 patients (mean age 50 years; 71% men), statin therapy in intermediate and high risk patients was shown to significantly reduce the risk of CVD events.19 The collective evidence from analysis of plaque composition in athletes4,10 and from clinical outcomes data9 supports the conclusion that at any given level of CAC, long-term exposure to high physical activity levels and greater overall fitness is protective, compatible with long-term health and confers a prognostic benefit. However, it cannot be understated that guideline pharmacological therapy should be initiated in athletes as in the general population. Whether athletes need different target levels to reduce endpoints is uncertain. CAC is a surrogate marker of atherosclerosis burden and a strong predictor of CVD risk, including in the subgroup of highly active individuals. Risk stratification can help direct lifestyle modifications and, if appropriate, initiation of pharmacologic therapy. CAC scoring and risk calculators engage patients in the process, encourage shared decision-making and increase the likelihood of adherence to a management strategy. With regard to exercise recommendations, higher physical activity is protective at any given level of CAC levels and thus should be encouraged. All authors contributed to this manuscript. KL did the literature search and drafted the manuscript. MH and JS reviewed and edited the manuscript. JAD supervised the writing process and made major contributions. All authors approved the final version of the manuscript. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.