Relative fat mass as a predictor of incident stroke: evidence from the PREVEND cohort

BACKGROUND AND AIMS: Relative fat mass (RFM), an adiposity index derived from waist circumference and height, has emerged as a strong and consistent marker of cardiometabolic risk. However, evidence on its association with incident stroke is limited. This study aimed to evaluate the associations of RFM with incident stroke and its subtypes. METHODS AND RESULTS: We included 7843 participants without a history of stroke and cardiovascular disease from the Prevention of Renal and Vascular End-stage Disease (PREVEND) community-based cohort (mean age 47.7 years, 51.3% women). Associations of RFM with incident outcomes were assessed using age- and sex-adjusted Cox regression models. Over a median follow-up period of 12.6 years, 196 participants (2.5%) experienced stroke, including 138 (70.4%) ischaemic events and 58 (29.6%) haemorrhagic events. RFM was associated with a 26% higher risk of stroke (hazard ratio per 1-SD [HR]: 1.26; 95%CI: 1.05-1.50); corresponding risk for body mass index, waist circumference, and waist-to-hip ratio were 12%, 15%, and 17% respectively. Additional adjustment for height-indexed creatinine excretion rate (CER-index), a surrogate for muscle mass, strengthened the associations of RFM (HR: 1.41; 95%CI: 1.28-1.70) and other anthropometric indices with incident stroke. Among stroke subtypes, RFM was significantly associated with ischaemic stroke (HR: 1.33; 95%CI: 1.08-1.65) but not with haemorrhagic stroke (HR: 1.10; 95%CI: 0.80-1.51), and additional adjustment for CER-index strengthened its association only for ischaemic stroke (HR: 1.55; 95%CI: 1.25-1.94). CONCLUSIONS: RFM is strongly associated with incident stroke, particularly ischaemic stroke, and accounting for muscle mass further strengthens this relationship. These findings support RFM as a clinically meaningful proxy of pathogenic adiposity and additionally highlight the importance of incorporating body composition, into cerebrovascular risk assessment.