Associations of body mass index and metabolic health with stroke risk in a large prospective cohort with time updated covariates.

The global prevalence of overweight and obesity is rising, and recent studies have established an independent contribution of adiposity to stroke risk. How the increased risk associated with adiposity relates to other factors including metabolic health is not fully understood. We analyzed 132,045 participants from the Northern Sweden Health and Disease Study with repeated health examinations (1985-2022). Stroke events were identified via national registers. Body mass index (BMI) was modeled as continuous (splines) and categorical (WHO definitions). Cox models with time-updated covariates estimated hazard ratios (HRs), and machine learning (XGBoost-AFT) assessed complex relationships. Over a median 20.2-year follow-up (2.67 million person-years), 7,493 strokes occurred. In fully adjusted models, overweight (HR: 1.14; 95% CI: 1.08-1.20) and obesity (HR: 1.36; 95% CI: 1.27-1.45) independently increased stroke risk versus normal weight. Poor metabolic health was also strongly associated (HR: 1.41 ; 95% CI: 1.34-1.49) with increased stroke risk. Combined obesity and poor metabolic health conferred the highest risk (HR: 1.79; 95% CI: 1.67-1.93). Age modified the association between higher BMI and stroke risk (p-interaction = 0.007), with stronger associations at younger ages. Machine learning confirmed the BMI-stroke risk pattern. In conclusion, overweight and obesity are associated with an independent stroke risk, even among younger and metabolically healthy individuals.