High-Volume Physical Activity and Clinical Coronary Artery Disease Outcomes: Findings From the Cooper Center Longitudinal Study

BACKGROUND: High-volume physical activity (PA) is associated with a higher prevalence of subclinical coronary artery disease (CAD). However, the clinical significance of subclinical CAD among high-volume exercisers remains incompletely understood, and the dose–response relationship between high-volume PA and clinical CAD events remains uncertain. METHODS: Individual participant data from the Cooper Center Longitudinal Study (1987–2018) were linked to Medicare claims files. PA volume was determined by self-report and categorized as <500, 500 to 1499, 1500 to 2999, and ≥3000 metabolic equivalent of task (MET)-minutes per week. Subclinical CAD (coronary artery calcium [CAC]) was measured by cardiac computed tomography. All other risk factors were measured in the standard fashion. Composite CAD events (acute myocardial infarction and revascularization) and all-cause mortality were determined from Medicare claims files. A multivariable-adjusted proportional hazards illness-death model with random shared frailty was used to estimate the association between PA volume, CAC, and both clinical CAD and death. Heterogeneity in the association between CAC and clinical CAD across levels of PA was determined with multiplicative interaction terms. RESULTS: We included 26724 participants (54 years of age; 28% women). Mean exercise volume was 1130 MET-minutes per week, with 1997 (7.5%) reporting ≥3000 MET-minutes per week. After a mean follow-up of 20.5 years, we observed 811 acute myocardial infarction events, 1636 composite CAD events, and 2857 deaths without CAD. Compared with individuals exercising <500 MET-minutes per week, the lowest risk for acute myocardial infarction occurred among individuals with intermediate PA volumes (500–1499 MET-minutes per week: hazard ratio [HR], 0.77 [95% CI, 0.65–0.91]; 1500–2499 MET-minutes per week: HR, 0.78 [95% CI, 0.63–0.95]). There was no association between high-volume PA (>3000 METminutesw per week) and risk for acute myocardial infarction (HR, 0.95 [95% CI, 0.72–1.25]). In contrast, the lowest risk for death was observed among the high-volume PA group (HR, 0.71 [95% CI, 0.60–0.83]). CAC (on log scale) was associated with a higher risk for composite CAD across all PA categories, including among the high-volume PA subgroup (HR, 1.29 [95% CI, 1.16–1.44]; P<0.001; P_interaction= 0.969). CONCLUSIONS: Compared with low-volume PA, high-volume PA was associated with a lower risk for all-cause mortality but a similar risk for clinical CAD. CAC was associated with an increased risk for clinical CAD regardless of the volume of PA.