Visceral fat metabolism score and cardiovascular-kidney-metabolic syndrome stages in all-cause and cause-specific mortality: insights from UK Biobank

The 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. 396,383 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. Over 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. High 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.