Waist-to-height ratio modifies the association between cardiometabolic indices and incident carotid plaque: evidence from a Chinese cohort

Background: Cardiometabolic indices and central obesity, often measured by waist-to-height ratio (WHtR), are both associated with carotid plaque (CP), but are usually analyzed separately. However, it remains unclear whether their combined effects-both additive and multiplicative-differ in relation to incident CP within the same population, and whether potential interactions exist. Methods: This retrospective cohort study was based on the Dalian Health Management Cohort. Cox proportional hazards models were used to assess the associations of cardiometabolic indices and WHtR with incident CP, and both additive and multiplicative models were applied to evaluate their joint effects and interactions. Time-dependent and time-weighted average exposure models based on repeated measurements were used to reduce regression dilution bias. Dose-response relationships were examined using restricted cubic splines. Predictive performance and clinical utility were further evaluated using time-dependent receiver operating characteristic curves, Harrell's C-index, decision curve analysis, and related metrics. Results: Among 6,984 participants, 1,198 incident CP cases occurred over a median follow-up of 2.4 years (incidence rate: 62.2 per 1,000 person-years). Multiple cardiometabolic indices were positively associated with the risk of incident CP. Multiplicative indices showed larger effect estimates than additive indices, with the highest risk observed for Castelli's Risk Index II (CRI-II)-WHtR in the top quartile (HR = 2.00, 95% CI 1.63-2.46), and similar effect sizes were observed in both sexes. Results were robust in time-dependent and time-weighted analyses, with a significant interaction between CRI-II and WHtR, and a non-linear association with CP risk. WHtR-based multiplicative composite indices demonstrated moderate discriminatory ability, with CRI-II-WHtR showing the best predictive performance (AUC = 0.770; Harrell's C-index = 0.739), along with modest clinical utility and risk stratification capacity. Conclusion: Cardiometabolic abnormalities and central obesity were jointly associated with a higher risk of incident CP, with a more pronounced association observed for the CRI-II-WHtR composite index. Further interaction analyses suggest a potential interaction between cardiometabolic abnormalities and central obesity in CP development. The predictive value of composite indices still requires further validation before clinical application.