Abstract
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome embodies the interconnection between cardiovascular, renal, and metabolic disorders. Anthropometric indices reflect distinct aspects of obesity and may aid in stratifying the severity of CKM syndrome and predicting mortality. Thus, this study aimed to assess and compare the relationships between multiple obesity-related measures and advanced CKM stages, as well as the risk of mortality. METHODS: Data included in this analysis were from the National Health and Nutrition Examination Survey (NHANES). Participants were categorized into quartiles (Q1-Q4) based on each anthropometric index. We estimated the associations with all-cause, cardiovascular, and non-cardiovascular mortality outcomes using Cox proportional hazards models, and evaluated the odds of an advanced CKM stage (stages 3/4) using logistic regression. Possible non-linear exposure-outcome patterns were further investigated through restricted cubic spline modelling. Then, to compare the predictive performance of the indices, we calculated the area under the receiver operating characteristic curve (AUC). RESULTS: We included 28,911 adults from the NHANES (1999-2018) (median age (interquartile range (IQR)) 55.0 (40.0-67.0) years, 52.5% male), comprising 21,789 in CKM stages 1-2 and 7122 in stages 3-4. The anthropometric indices varied significantly across CKM stages (p < 0.001), with body mass index, waist circumference, Weight-adjusted Waist Index (WWI), and relative fat mass increasing with disease severity. In stages 1-2, the highest quartile (Q4) of A Body Shape Index (ABSI), WWI, waist-to-height ratio (WHtR), and Conicity Index (C-index) was associated with higher all-cause and cardiovascular mortalities, often following U-shaped or J-shaped non-linear patterns. In stages 3-4, predictive strength diminished, with only the ABSI and WWI showing consistent associations with mortality. For CKM progression, the ABSI (AUC = 0.73), WWI (AUC = 0.70), and C-index (AUC = 0.69) demonstrated the best discrimination. CONCLUSIONS: This study shows that several anthropometric indices, particularly the ABSI, WWI, WHtR, and C-index, are strongly associated with advanced CKM stage and increased mortality risk. These associations were stronger for central adiposity measures than for general adiposity, suggesting the potential relevance of central fat distribution and supporting the possible role of anthropometric indices in early risk stratification and targeted intervention in CKM syndrome.