Mediating role of arterial stiffness in the association between physical activity and cardiovascular disease risk: a prospective cohort study

Estimated pulse wave velocity (ePWV), a noninvasive marker of arterial stiffness, serves as a potential biomarker for cardiovascular disease (CVD) risk. This 7 year prospective cohort study of 10,055 adults aged 35-75 investigated whether ePWV mediates the association between physical activity (PA) and CVD risk. PA levels (high/moderate/low in 2016), ePWV (measured in 2018), and CVD incidence (2018-2023) were defined as exposure, mediator, and outcome, respectively. Cox models and causal mediation analysis (CMA) assessed associations and the natural indirect effect (NIE) of PA on CVD via ePWV. During follow-up, CVD incidence was 1.29/100 person-years. Elevated ePWV (≥ 10 m/s) significantly increased CVD risk (HR = 1.673, 95% CI 1.319, 2.124). ePWV may mediate the link between low/moderate PA and CVD incidence. In the high ePWV group (≥ 10 m/s), low/moderate PA levels showed an NIE of HR = 1.025 (95% CI 1.013, 1.041), with 10.6% of the effect mediated by ePWV. Arterial stiffness appears to mediate the association between PA and incident CVD in middle-aged and older adults. These findings highlight ePWV as a potential metric for CVD risk prediction, and future validation in randomized settings is required before considering clinical utility.