Metabolic Vulnerability Index and Risk of Total Mortality: Findings From the Multi-Ethnic Study of Atherosclerosis

BACKGROUND: The metabolic vulnerability index (MVX) is a composite score reflecting inflammatory, metabolic, and nutritional status. The objective of this study is to evaluate the association between MVX and mortality among adults without prevalent cardiovascular disease (CVD). METHODS: Using the MESA (Multi-Ethnic Study of Atherosclerosis), we examined 5887 adults from all participating MESA sites free of clinical CVD at baseline (2000-2002). MVX was measured using nuclear magnetic resonance metabolomics and included GlycA, small high-density lipoprotein particles, valine, leucine, isoleucine, and citrate. We assessed the association between MVX (categorized as quartiles; quartile 1 as referent) and total mortality (median follow-up, 17.9 years). Cox regression models adjusted for sociodemographic measures, behaviors, cardiometabolic factors, and incident disease were used to estimate hazard ratios. Analyses were repeated, stratified by incident CVD. RESULTS: Among 5887 participants (mean age 61.6, 53% self-identified female), MVX scores ranged from 7.8 to 79.3, and mortality increased from 19.5% to 37.4% across quartiles during 94 351 person-years of follow-up. CVD- and non-CVD-related deaths separately demonstrated similarly higher rates in higher quartiles of MVX. Participants in the fourth quartile of MVX had a significantly higher risk for total mortality (hazard ratio, 1.73 [95% CI, 1.49-2.01]) during follow-up with minimal attenuation after adjustment for incident disease. In those with and without incident CVD during follow-up, the hazard ratio for mortality in the fourth quartile was 1.74 (95% CI, 1.38-2.20) and 1.68 (95% CI, 1.38-2.05), indicating a strong association with increased risk of death irrespective of CVD events. CONCLUSIONS: Among mid-life adults free of clinical CVD at baseline, higher MVX scores were strongly and independently associated with future mortality, irrespective of incident morbidity-including CVD. These findings suggest that the MVX score offers unique insight into an individual's vulnerability to mortality beyond traditional risk factors and disease status.