Physical exercise volume, type, and intensity and risk of all-cause mortality and cardiovascular events in patients with cardiovascular disease: a mediation analysis.

Abstract Aims To estimate the relation between physical exercise volume, type, and intensity with all-cause mortality and recurrent vascular events in patients with cardiovascular disease (CVD) and to quantify to what extent traditional cardiovascular risk factors mediate these relations. Methods and results In the prospective UCC-SMART cohort (N = 8660), the associations of clinical endpoints and physical exercise volume (metabolic equivalent of task hours per week, METh/wk), type (endurance vs. endurance + resistance), and intensity (moderate vs. vigorous) were estimated using multivariable-adjusted Cox models. The proportion mediated effect (PME) through body mass index, systolic blood pressure, low-density lipoprotein cholesterol, insulin sensitivity, and systemic inflammation was assessed using structural equation models. Sixty-one percent of patients (73% male, age 61 ± 10 years, >70% receiving lipid-lowering and blood pressure–lowering medications) reported that they did not exercise. Over a median follow-up of 9.5 years [interquartile range (IQR) 5.1–14.0], 2256 deaths and 1828 recurrent vascular events occurred. The association between exercise volume had a reverse J-shape with a nadir at 29 (95% CI 24–29) METh/wk, corresponding with a HR 0.56 (95% CI 0.48–0.64) for all-cause mortality and HR 0.63 (95% CI 0.55–0.73) for recurrent vascular events compared with no exercise. Up to 38% (95% CI 24–61) of the association was mediated through the assessed risk factors of which insulin sensitivity (PME up to 12%, 95% CI 5–25) and systemic inflammation (PME up to 18%, 95% CI 9–37) were the most important. Conclusion Regular physical exercise is significantly related with reduced risks of all-cause mortality and recurrent vascular events in patients with CVD. In this population with high rates of lipid-lowering and blood pressure–lowering medication use, exercise benefits were mainly mediated through systemic inflammation and insulin resistance.