A vascular-muscle-adiposity phenotype and incident stroke risk in middle-aged and older adults: a multi-cohort study

Blood pressure, muscle function and central adiposity are routinely measurable but are usually examined as separate risk domains. We analysed harmonised data from the China Health and Retirement Longitudinal Study (CHARLS), the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS) to test whether a rule-based vascular-muscle-adiposity adverse-count phenotype was associated with incident stroke in middle-aged and older adults. The baseline analytic cohort included 40,520 participants, and the incident stroke risk set included 38,795 participants. The phenotype assigned one point for each adverse dimension: high mean arterial pressure, low maximum grip strength and high waist-to-height ratio, defined using cohort- and sex-specific tertiles. Cohort-specific Cox models were pooled by random-effects meta-analysis. During follow-up, 2011 incident strokes occurred. Adjusted hazard ratios per 1-step increase were 1.32 (95% CI 1.22-1.44) in CHARLS, 1.44 (95% CI 1.23-1.68) in ELSA and 1.22 (95% CI 1.14-1.32) in HRS. The pooled hazard ratio per 1-step increase was 1.30 (95% CI 1.20-1.41), and the pooled hazard ratio for 3 versus 0 adverse dimensions was 1.94 (95% CI 1.60-2.36). All-cause mortality associations were less consistent across cohorts. This three-component phenotype may offer a reproducible way to summarise vascular, muscular and adiposity-related susceptibility to incident stroke in later adulthood; it should not be interpreted as a clinical threshold without adjudicated outcome validation.