Body composition phenotypes are key predictors of cardiovascular-kidney-metabolic multimorbidity and long-term mortality: insights from a population-based cohort study.

AIMS: Cardiovascular-kidney-metabolic (CKM) syndrome is associated with increased risks of cardiovascular disease (CVD) and all-cause mortality, but its relationship with body composition phenotypes remains unclear. MATERIALS AND METHODS: This population-based cohort study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018, linked to the National Death Index through December 31, 2019. Participants were stratified on body mass index (BMI) and waist-to-height ratio (WHtR): (1) obesity with central adiposity (high BMI, high WHtR), (2) obesity without central adiposity (high BMI, low WHtR), (3) normal weight with central adiposity (normal BMI, high WHtR), and (4) normal weight without central adiposity (normal BMI, low WHtR). CKM multimorbidity was defined as ≥ 2 of hypertension, hyperlipidemia, diabetes, chronic kidney disease, and/or CVD. Primary and secondary outcomes were all-cause and cardiovascular mortality. Associations were assessed using survey-weighted Cox proportional hazards models. RESULTS: The weighted cohort represented 106.9 million US adults (mean age 47.2). Majority were normal weight without central adiposity (53.3%), followed by obesity with central adiposity (33.9%), normal weight with central adiposity (8.1%), and obesity without central adiposity (4.7%). Normal weight with central adiposity had highest CKM multimorbidity (46.5%), risk of all-cause mortality (adjusted hazard ratio [aHR] 1.87, 95% CI 1.08-3.25, p = 0.025) and cardiovascular mortality (aHR 7.76, 95% CI 1.01-59.76, p = 0.049). The Kaplan-Meier curves demonstrate that individuals with both CKM multimorbidity and normal weight with central adiposity demonstrated the poorest long-term survival (p < 0.001). CONCLUSIONS: Normal weight individuals with central adiposity bear the greatest CKM burden and mortality risk, highlighting limitations of BMI-based risk assessment.