Does a modified metabolic syndrome definition improve prediction of cardiovascular events and mortality? findings from a 17-year cohort study

BACKGROUND: Metabolic syndrome (MetS) criteria include central obesity assessed by waist circumference (WC), which may be confounded by body weight. We evaluated whether substituting the weight-adjusted waist index (WWI) for WC improves prediction of long-term cardiovascular disease (CVD) events and mortality. OBJECTIVES: To compare the prognostic performance of a WWI-based MetS definition versus the classic WC-based MetS definition for predicting CVD events and mortality, utilizing 17 years of follow-up data from the Isfahan Cohort Study (ICS). METHODS: Of the 6,504 participants aged ≥ 35 years without prior CVD at baseline, 919 (14.1%) were lost to follow-up over 17 years. The remaining 5,585 participants were included in the final analysis. The classic and modified MetS definitions were compared using Cox regression analysis, Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, and risk reclassification by net reclassification improvement (NRI) for CVD events, CVD mortality, and all-cause mortality. RESULTS: The modified WWI-based MetS reclassified approximately 9.2% of participants and significantly improved risk classification for incident CVD events (NRI = + 0.41, p < 0.0001). In crude analyses, the modified MetS was associated with higher risk of incident CVD events compared to the classic definition. After full adjustment, associations attenuated but remained significant for CVD events (modified HR 1.19, 95% CI: 1.01-1.41; classic HR 1.25, 95% CI: 1.06-1.47), whereas associations with CVD and all-cause mortality lost significance. Kaplan-Meier analyses confirmed significant differences in survival by MetS status for both definitions. The modified definition demonstrated modest improvements in sensitivity, specificity, accuracy, and area under the ROC curve (AUC) (CVD events: 0.62 vs. 0.60; CVD mortality: 0.63 vs. 0.59; all-cause mortality: 0.59 vs. 0.55) for all outcomes compared to the classic definition. CONCLUSION: In this 17-year cohort, replacing WC with WWI in the MetS definition modestly improved prediction of cardiovascular events and mortality. Using WWI in MetS criteria may enhance risk stratification in clinical practice. Further studies are needed to validate these findings across diverse populations.