Dynapenic-metabolic obesity and incident stroke in middle-aged and older adults: The mediating role of intrinsic capacity and systemic inflammation

BACKGROUND: Conventional obesity definitions overlook heterogeneity related to metabolic health and muscle strength. This study examined the associations between dynapenic-metabolic obesity (DMO) and incident stroke among middle-aged and older Chinese adults. METHODS: Our study included 11,770 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018) with 2011 as baseline. Dynapenia was defined by handgrip strength (<28 kg for men, <18 kg for women); metabolic dysfunction by ≥2 of 4 criteria (hypertension, dyslipidemia, impaired glycemia, or low HDL-C); and obesity by BMI ≥25 kg/m² (general obesity) or waist circumference ≥ 90 cm for men and ≥ 85 cm for women (abdominal obesity). Cox models estimated hazard ratios (HRs) for stroke, adjusting for covariates. Mediation analysis evaluated the roles of C-reactive protein (CRP) and intrinsic capacity (IC). RESULTS: During follow-up, 787 participants (6.7%) experienced stroke. Obesity alone, without dynapenia or metabolic dysfunction, was associated with elevated stroke risk (general obesity: HR 1.50, 95% CI 1.15-1.95; abdominal obesity: HR 1.55, 95% CI 1.21-1.98). The highest risk was observed in participants with combined dynapenia and metabolic dysfunction (DMGO: HR 2.97, 95% CI 2.01-4.37; DMAO: HR 2.96, 95% CI 2.08-4.21). Mediation analyses indicated that systemic inflammation and reduced intrinsic capacity partially explained these associations. Findings were consistent across subgroups and sensitivity analyses. CONCLUSIONS: Dynapenic-metabolic obesity is strongly associated with incident stroke, but even obesity alone increases risk. Systemic inflammation and impaired intrinsic capacity partially mediate these effects, highlighting the importance of integrated strategies targeting adiposity, metabolic health, and muscle function to prevent stroke in aging populations.