Abstract / Summary
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.