Cardiovasc Diabetol. 2026 Jun 29. doi: 10.1186/s12933-026-03277-y. Online ahead of print.
ABSTRACT
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is recognized as a progressive pathophysiological continuum linking metabolic dysfunction, dysfunctional adiposity, chronic kidney disease, and cardiovascular injury. The atherogenic index of plasma (AIP) reflects lipid-related atherogenic burden, whereas novel adiposity indices, including body roundness index (BRI), weight-adjusted waist index (WWI), and a body shape index (ABSI), capture body-shape-related adiposity burden. However, the associations of AIP and AIP-based adiposity composite indices with mortality outcomes across the CKM spectrum remain unclear. This study aimed to evaluate the associations of AIP and integrative AIP-based composite indices, including AIP-BRI, AIP-WWI, and AIP-ABSI, with all-cause and cardiovascular mortality among individuals across CKM stages.
METHODS: We conducted a retrospective cohort analysis using prospectively collected data from 22,587 US adults in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Following the 2023 American Heart Association (AHA) Presidential Advisory, participants were classified into a hierarchical staging framework (Stages 0-4) to reflect the CKM disease continuum. Primary outcomes were all-cause and cardiovascular mortality, identified through linkage to the National Death Index. Integrative AIP-based composite indices were constructed by directly multiplying AIP by each adiposity index, including BRI, WWI, and ABSI, yielding AIP-BRI, AIP-WWI, and AIP-ABSI, respectively. These indices were evaluated as integrated exposure variables reflecting the combined burden of atherogenic dyslipidemia and adiposity-related body shape. All analyses incorporated complex survey weights to ensure national representativeness. Survey-weighted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Model 2 adjusted for demographic and socioeconomic characteristics, lifestyle factors, blood pressure, and total cholesterol. Nonlinear associations were examined using restricted cubic splines (RCS). Incremental prognostic value was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
RESULTS: During follow-up, non-survivors exhibited significantly higher baseline integrative composites than survivors (P < 0.001). In the fully adjusted model (Model 2), which adjusted for demographic and socioeconomic characteristics, lifestyle factors, blood pressure, and total cholesterol, each standard deviation increase in the integrative composites was independently associated with a higher risk of all-cause mortality: AIP-BRI (HR, 1.09; 95% CI, 1.05-1.14), AIP-WWI (HR, 1.07; 95% CI, 1.02-1.11), and AIP-ABSI (HR, 1.07; 95% CI, 1.02-1.11). These point estimates were numerically slightly higher than that of stand-alone AIP (HR, 1.06; 95% CI, 1.01-1.10), but the differences should be interpreted cautiously. For cardiovascular mortality, the corresponding HRs were 1.17 (95% CI, 1.09-1.27) for AIP-BRI, 1.11 (95% CI, 1.03-1.21) for AIP-WWI, and 1.11 (95% CI, 1.02-1.20) for AIP-ABSI, compared with 1.10 (95% CI, 1.02-1.20) for AIP. RCS analyses revealed J-shaped associations, with a clinical risk threshold for AIP-BRI at 1.57. Subgroup analyses indicated that these associations were most evident in participants aged < 50 years. Adding BRI to AIP assessment yielded a statistically significant but modest NRI of 3.10% for cardiovascular mortality.
CONCLUSION: Across the CKM spectrum, higher AIP-based adiposity composite indices, particularly AIP-BRI, were associated with increased risks of all-cause and cardiovascular mortality, especially among younger individuals. However, their incremental predictive improvement was modest, suggesting that these indices may serve as supplementary exploratory markers rather than stand-alone tools for CKM risk stratification.
PMID:42374419 | DOI:10.1186/s12933-026-03277-y