Abstract
BackgroundThe roles of Cardiovascular-Kidney-Metabolic Syndrome (CKM) staging and the emerging obesity marker Visceral Fat Metabolism Score (METS-VF) in cause-specific mortality, as well as their potential interaction, remain to be further investigated.Methods396,383 UK Biobank participants were analyzed. Primary outcomes included all-cause and cause-specific deaths, including cardiovascular, respiratory, digestive, neurodegenerative diseases, cancer, and other causes. Independent and joint effects of METS-VF and CKM were evaluated using a COX proportional hazards regression model, with multiple sensitivity analyses conducted to verify robustness. Dose-response relationships were visualized using restricted cubic spline (RCS) curves. Receiver operating characteristic (ROC) analyses were conducted to evaluate the discriminative performance of METS-VF for predicting mortality compared with other obesity-related indices. Multiple sensitivity analyses were further performed to assess the robustness of the findings.ResultsOver an average follow-up of 12.51 years, 34,471 deaths were recorded. After multivariate adjustment, both METS-VF and CKM stage were associated with all-cause mortality. The hazard ratio for the highest METS-VF quartile was 1.70 (95% CI: 1.61-1.80), and for the highest CKM stage was 2.23 (95% CI: 2.12-2.35). Each 0.1 increase in METS-VF raised the risk of death by 8.2% (CVD), 3.5% (respiratory), 8.8% (digestive), 2.7% (cancer), and 6.9% (other causes). RCS analysis showed a non-linear relationship between METS-VF and mortality. ROC analyses further demonstrated that METS-VF exhibited significantly higher predictive performance for both all-cause and cause-specific mortality compared to other obesity-related indices. Joint analysis revealed that participants with stage IV CKM and high METS-VF had the highest risks of all-cause and cause-specific mortality, with synergistic effects noted for CVD, and digestive mortality.ConclusionHigh METS-VF and late-stage CKM were associated with increased risks of mortality from multiple causes. For individuals with late-stage CKM, enhanced assessment of METS-VF is recommended to facilitate timely interventions and reduce mortality risk.