Refining the criteria of cardiovascular-kidney-metabolic syndrome stage 0-3: the incremental reclassification value of excessive adiposity in a nationwide NHANES cohort
H X Yu, Z Ren, Y Li, P Mao, Y Wang, W LiuAbstract
Background
Cardiovascular-Kidney-Metabolic (CKM) syndrome is a leading determinant of premature morbidity and mortality worldwide. Currently, the CKM staging criteria primarily relied on body mass index (BMI) to define adiposity-related risks. However, BMI-based measures of obesity can both underestimate and overestimate adiposity thus cardiometabolic risk. Updated Lancet Commission diagnosis criteria of clinical obesity emphasized the use of alternative anthropometric criteria beyond BMI.
Purpose
It remains unclear whether novel indices of excessive adiposity, such as the waist circumference (WC) and body roundness index (BRI) and waist-to-height ratio (WHtR), can better optimize risk stratification in early-stage CKM. We aimed to investigate incremental reclassification value of novel anthropometric measures in refining the current CKM syndrome stage 0-3.
Methods
Using nationally representative data from the National Health and Nutrition Examination Survey (NHANES, 2011-2020), we included 16,069 adult participants with CKM stage 0-3. To evaluate the incremental reclassification value of novel adiposity indices for predicting 10-year all-cause and cardiovascular mortality, we constructed three multivariable Cox proportional hazards models. All models were adjusted for an identical set of core covariates (including age, sex, BMI, hypertension, diabetes, and eGFR). Model performance was compared using Harrell’s C-index, calibration plots, and Net Reclassification Improvement (NRI).
Results
At baseline, participants in the high WHtR and BRI groups exhibited higher blood pressure, reduced renal function, and a higher prevalence of prediabetes. While models substituting traditional WC with WHtR or BRI maintained robust predictive performance for 10-year mortality, an important prognostic paradox emerged. Although the BRI-incorporated model yielded better overall discrimination (C-index) for both all-cause and cardiovascular mortality, substituting WC with either WHtR or BRI resulted in a negative NRI (-0.04) compared to the traditional BMI+WC model.
Conclusion
Despite slightly superior statistical discrimination, novel adiposity indices like WHtR and BRI fail to provide true incremental reclassification value for patients in CKM stage 0-3. These novel metrics introduce a critical clinical risk of erroneously up-classifying low-risk individuals.Calibration Plot