Joint Associations of Circadian Syndrome and Physical Activity with Incident Stroke in Middle-Aged and Older Adults: A Prospective Cohort Study

Background Circadian syndrome (CircS), defined by the co-occurrence of sleep disturbance, depressive symptoms, central obesity, hypertension, impaired glucose metabolism, and dyslipidemia, reflects systemic circadian and metabolic dysregulation. Although physical activity (PA) may reinforce circadian alignment, whether it modifies the association between CircS and incident stroke remains unclear. Methods We analyzed data from 3,135 participants aged 45 years or older with no history of stroke at baseline in the China Health and Retirement Longitudinal Study (CHARLS). Baseline data were collected in 2011, and follow-up continued through 2018. CircS was defined using established criteria as the presence of at least 4 of 7 components. PA was categorized as physically active or physically inactive according to self-reported activity frequency. Participants were classified into four joint exposure groups according to CircS and PA status. Incident stroke was ascertained by self-reported physician diagnosis during follow-up. Associations were assessed using Cox proportional hazards models with sequential adjustment for demographic, socioeconomic, and lifestyle factors. Subgroup and sensitivity analyses were performed to assess the robustness of the findings. Results Over a median follow-up of 6.4 years, 236 incident stroke events occurred. Participants with CircS and physical inactivity had the highest stroke incidence. In fully adjusted models, compared with this reference group, the risk of incident stroke was lower among participants without CircS who were physically inactive (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.31–0.72), participants without CircS who were physically active (HR, 0.24; 95% CI, 0.16–0.36), and participants with CircS who were physically active (HR, 0.61; 95% CI, 0.43–0.87). A significant trend was observed across the joint exposure categories (P for trend < 0.001). Subgroup and sensitivity analyses yielded similar results. Conclusions In this cohort of middle-aged and older Chinese adults, CircS was associated with a higher risk of incident stroke, whereas PA was associated with a lower risk. Participants without CircS who were physically active had the lowest observed risk; among participants with CircS, physical activity was also associated with a lower risk of stroke than physical inactivity. Integrating circadian health assessment with PA promotion may be a useful approach to stroke prevention in aging populations. Trial registration Not applicable.