Metabolic Vulnerability Index predicts mortality in older adults based on markers of inflammation and dysmetabolism

Traditional clinical metrics fail to capture the complex interplay among metabolic health, inflammation, and nutritional status contributing to aging-related morbidity and mortality. The Metabolic Vulnerability Index (MVX) integrates measures of inflammation and metabolic health to assess mortality risk. Using clinical nuclear magnetic resonance spectra and a validated MVX algorithm, MVX scores were generated for the Duke Established Populations for Epidemiologic Studies of the Elderly (D-EPESE) longitudinal cohort (n = 1507, mean age 78.1 ± 5.4 years; 36% men). MVX comprises markers of chronic inflammation (small high density lipoproteins and the inflammation marker, GlycA) and metabolic malnutrition (citrate and branched chain amino acids). Incident all-cause deaths were ascertained over a median follow-up of 7.0 years (95% confidence interval (CI):1.0–18.9). In models adjusted for age, sex, and race, greater MVX scores were strongly associated with 1-year mortality [hazard ratio (HR) per 1 standard (SD): 3.00 (CI: 2.34–3.85, p < 0.0001)]. After further adjustment for body mass index, type 2 diabetes, smoking, systolic blood pressure, total cholesterol, triglycerides, eGFR, and qualitative measures of health and physical function, the association persisted, with only modest attenuation [HR: 2.35 (CI: 1.76–3.14, p < 0.0001)]. Similar associations were observed for 2-, 5- and 10-year mortality, with some attenuation over longer follow-up. Participants in the greatest MVX quartile had significantly greater mortality risk (Kaplan-Meier, p < 0.0001). The 1-year AUROC for mortality was 0.77 (CI: 0.71–0.84), outperforming questionnaire-based measures of health and physical function, as well as the individual MVX components (p < 0.0001). Our findings suggest that MVX is a prognostic, biomarker-derived test that integrates markers of inflammation, metabolic dysfunction, and malnutrition to predict short- and long-term mortality in adults >70 years. MVX may provide additional clinical information to support personalized risk stratification and guide targeted approaches for older adults.