Megan M Marron1, Tamara B Harris2, Robert M Boudreau1, Clary B Clish3, Steven C Moore4, Rachel A Murphy5, Venkatesh L Murthy6, Jason L Sanders7, Ravi V Shah8, George C Tseng9,10, Stacy G Wendell11, Joseph M Zmuda1,10, Anne B Newman1,10. 1. Department of Epidemiology, University of Pittsburgh, Pennsylvania. 2. Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland. 3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts. 4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. 5. Centre of Excellence in Cancer Prevention, School of Population and Public Health, University of British Columbia, Vancouver, Canada. 6. Division of Cardiovascular Medicine, University of Michigan at Ann Arbor, Michigan. 7. Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 8. Department of Medicine, Massachusetts General Hospital, Boston. 9. Department of Biostatistics, University of Pittsburgh, Pennsylvania. 10. Department of Medicine, University of Pittsburgh, Pennsylvania. 11. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pennsylvania.
Abstract
BACKGROUND: Frailty is more prevalent among black versus white older Americans. We previously identified 37 metabolites associated with the vigor to frailty spectrum using the Scale of Aging Vigor in Epidemiology (SAVE) among older black men from the Health, Aging, and Body Composition (Health ABC) study. Here, we sought to develop a metabolite composite score based on the 37 SAVE-associated metabolites and determine whether the composite score predicts mortality and whether it attenuates the association between frailty and mortality among older black men. METHODS: Plasma metabolites were measured using liquid chromatography-mass spectrometry. Most of the 37 metabolites were organic acids/derivatives or lipids. Metabolites were ranked into tertiles: tertiles associated with more vigorous SAVE scores were scored 0, mid-tertiles were scored 1, and tertiles associated with frailer SAVE scores were scored 2. Composite scores were the sum of metabolite tertile scores. We examined mortality associations using Cox regression. Percent attenuation estimated the extent to which metabolites attenuated the association between frailty and mortality. RESULTS: One standard deviation frailer SAVE was associated with 30% higher mortality, adjusting for age and site (p = .0002); this association was attenuated by 56% after additionally adjusting for the metabolite composite score. In this model, one standard deviation higher metabolite composite score was associated with 46% higher mortality (p < .0001). Metabolite composite scores also predicted mortality (p = .045) in a validation sample of 120 older adults (40% men, 90% white). CONCLUSION: These metabolites may provide a deeper characterization of the higher mortality that is associated with frailty among older adults.
BACKGROUND: Frailty is more prevalent among black versus white older Americans. We previously identified 37 metabolites associated with the vigor to frailty spectrum using the Scale of Aging Vigor in Epidemiology (SAVE) among older black men from the Health, Aging, and Body Composition (Health ABC) study. Here, we sought to develop a metabolite composite score based on the 37 SAVE-associated metabolites and determine whether the composite score predicts mortality and whether it attenuates the association between frailty and mortality among older black men. METHODS: Plasma metabolites were measured using liquid chromatography-mass spectrometry. Most of the 37 metabolites were organic acids/derivatives or lipids. Metabolites were ranked into tertiles: tertiles associated with more vigorous SAVE scores were scored 0, mid-tertiles were scored 1, and tertiles associated with frailer SAVE scores were scored 2. Composite scores were the sum of metabolite tertile scores. We examined mortality associations using Cox regression. Percent attenuation estimated the extent to which metabolites attenuated the association between frailty and mortality. RESULTS: One standard deviation frailer SAVE was associated with 30% higher mortality, adjusting for age and site (p = .0002); this association was attenuated by 56% after additionally adjusting for the metabolite composite score. In this model, one standard deviation higher metabolite composite score was associated with 46% higher mortality (p < .0001). Metabolite composite scores also predicted mortality (p = .045) in a validation sample of 120 older adults (40% men, 90% white). CONCLUSION: These metabolites may provide a deeper characterization of the higher mortality that is associated with frailty among older adults.
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Authors: Megan M Marron; Tamara B Harris; Robert M Boudreau; Clary B Clish; Steven C Moore; Rachel A Murphy; Venkatesh L Murthy; Jason L Sanders; Ravi V Shah; George C Tseng; Stacy G Wendell; Joseph M Zmuda; Anne B Newman Journal: Metabolites Date: 2019-04-30