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.