Abstract
BACKGROUND: The Zhejiang University (ZJU) Index, a composite metabolic indicator incorporating body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), and alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, is associated with abnormalities like dyslipidemia and glucose intolerance. Yet its clinical significance in cardiovascular disease (CVD) is underinvestigated, and this study aims to clarify its associations with prevalent CVD, all-cause mortality, and CVD mortality. METHODS: The study included 18,609 adults from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018. Associations of the ZJU Index with prevalent CVD were evaluated using multivariable Logistic regression. Associations with all-cause mortality and CVD mortality were assessed using multivariable Cox proportional hazards regression. Restricted cubic spline (RCS) regression and ROC curve analyses were further used to explore non-linear relationships and predictive performance, respectively. Sensitivity analyses, which included excluding participants who died within 2 years and those with baseline CVD, confirmed the robustness of the findings. RESULTS: Among 18,609 participants, 2,121 had CVD (9.0% weighted prevalence). Logistic regression showed a positive association of the ZJU Index with prevalent CVD risk: after full adjustment, a 1-unit increase was linked to a 2% higher risk (OR = 1.02, 95% CI 1.01-1.03, P < 0.001), and participants in the highest quartile (Q4) had a 50% higher risk than those in the lowest quartile (Q1) (OR = 1.50, 95% CI 1.22-1.84, P < 0.001). Significant non-linearity between the ZJU Index and prevalent CVD was confirmed (P < 0.001). Over a median 71-month follow-up (36-121 months), 2,752 all-cause deaths (11.1% weighted rate) and 934 CVD deaths (3.4% weighted rate) occurred. After full adjustment, the association persisted for CVD mortality (Q4 vs. Q1: HR = 1.30, 95% CI 1.03-1.63, P = 0.027). Restricted cubic spline (RCS) analysis revealed that the ZJU Index had a U-shaped relationship with all-cause mortality and a J-shaped relationship with CVD mortality (both P < 0.001). Sensitivity analyses supported the robustness of these findings. CONCLUSIONS: In conclusion, whether analyzed as a continuous or categorical variable, a higher ZJU Index is significantly associated with higher risks of CVD and CVD mortality, while it shows a U-shaped relationship with all-cause mortality. This indicates that the ZJU Index holds potential as a CVD risk stratification tool to identify high-risk individuals and guide targeted interventions. However, its utility as a CVD screening tool requires further validation to confirm optimal cut-offs and compatibility with existing protocols.