Metabolic score for visceral fat profiles and incident cardiovascular disease in adults with CKM syndrome stages 0-3: a CHARLS longitudinal study.

BACKGROUND

The Metabolic Score for Visceral Fat (METS-VF) is a novel index reflecting visceral adiposity and metabolic dysfunction, but its association with incident cardiovascular disease (CVD) in adults with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0-3 remains unclear. This study aimed to explore this association and quantify the mediating effect of estimated glucose disposal rate (eGDR).

METHODS

Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS), we prospectively followed 3,815 adults with CKM syndrome stages 0-3 (baseline 2015) until 2020. The METS-VF profiles comprised baseline METS-VF, cumulative METS-VF, and change patterns identified by latent class growth modeling (LCGM). To investigate associations and underlying mechanisms, Cox proportional-hazards regression, weighted quantile sum (WQS) regression, and mediation analysis were employed. Sensitivity analyses (stratification by CKM syndrome stage and demographics, inverse probability weighting [IPW], Fine-Gray model) were used to support the robustness of the results.

RESULTS

Over a mean 4.4-year follow-up, 18.7% of participants developed CVD. In the fully adjusted model, elevated METS-VF profiles were associated with an increased risk of CVD: baseline METS-VF in the fourth quartile (HR = 1.615, 95% confidence interval (CI): 1.243-2.097), cumulative METS-VF in the fourth quartile (HR = 1.824, 95% CI: 1.397-2.381), and stable high-level METS-VF (Class 3) (HR = 1.288, 95% CI: 1.033-1.610). All associations remained significant following false discovery rate (FDR) correction. Stratified analyses showed stronger associations between METS-VF profiles and incident CVD in late-stage (vs. early-stage) CKM syndrome, with the association more pronounced in males-females only had significant associations in the highest quartile. WQS regression identified Metabolic Score for Insulin Resistance (METS-IR) as the primary contributing factor, with weights of 0.397 in 2011 and 0.375 in 2015. Mediation analysis indicated that eGDR mediated 65.38% of the baseline and 56.72% of the cumulative effects (both P < 0.001). Supplementary mediation analysis using body mass index (BMI)-based METS-VFBMI produced consistent findings.

CONCLUSIONS

METS-VF profiles are independently associated with incident CVD in CKM syndrome stages 0-3, more strongly in late stages. eGDR significantly mediates this relationship, supporting the "obesity-metabolism-vascular" axis. METS-VF may aid CVD risk stratification in CKM syndrome populations, and targeting insulin sensitivity may mitigate CVD risk.