A NOVEL METABOLITE COMPOSITE SCORE EXPLAINS THE HIGHER MORTALITY ASSOCIATED WITH FRAILTY AMONG OLDER BLACK MEN

Frailty is more prevalent among black versus white older Americans. We previously sought to better characterize frailty among 287 black men ages 70-81 by identifying 37 plasma metabolites associated with vigor to frailty using the scale of aging vigor in epidemiology (SAVE). Using this information, we developed a metabolite score to determine if it explained the frailty-associated higher mortality. The Human Metabolome Database classified the metabolites as organic acids/derivatives (m=14), lipids/lipid-like molecules (m=12), organoheterocyclic compounds (m=4), benzenoids (m=3), organic nitrogen compounds (m=2), organic oxygen compounds (m=1), and nucleosides/nucleotides/analogues (m=1). Values for each were ranked into tertiles. The metabolite tertile associated with more vigorous SAVE scores was given a score of 0, the metabolite mid-tertile a score of 1, and the metabolite tertile associated with frailer SAVE scores a score of 2. The metabolite composite score was calculated as the sum of the metabolite tertile scores. One standard deviation frailer SAVE was associated with 30% higher mortality (p=0.0002), adjusting for age and study site. The association between frailty and mortality was attenuated by 56% after additionally adjusting for the metabolite score, where organic acids/derivatives and lipids/lipid-like molecules (mostly amino acids, glycerophospholipids, sphingolipids) accounted for most of the attenuation. In this model, one standard deviation higher metabolite score was associated with 46% higher mortality (p<0.0001). The metabolite score also predicted mortality among 48 community-dwelling (96% white) older men (p=0.03). These metabolites provide a deeper characterization of frailty that reproducibly explains a substantial portion of the vulnerability to death in these older men.