title: Plasma-free fatty acids, fatty acid-binding protein 4, and mortality in older adults (from the Cardiovascular Health Study).
abstract: Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes, but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992 to 1993 as part of the Cardiovascular Health Study, an observational cohort of community-dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio [HR] per SD: 1.14, 95% confidence interval [CI] 1.09 to 1.18), but FABP4 levels were not (HR 1.04, 95% CI 0.98 to 1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death because of cardiovascular disease, dementia, infection, and respiratory causes but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p = 0.45), but FABP4 appeared to be associated with total mortality differentially in men and women (HR 1.17, 95% CI 1.08 to 1.26 for men; HR 1.02, 95% CI 0.96 to 1.07 for women, interaction p value <0.001). In conclusion, in a cohort of community-dwelling older subjects, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and noncardiovascular mortality.
authors: Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Boston Veterans Affairs Healthcare System, Boston, Massachusetts; Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Minneapolis, Minnesota. Electronic address: mdm307@mail.harvard.edu.
authors: Michael D
authors: MD
authors: Miedema
authors: Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington.
authors: Marlena
authors: M
authors: Maziarz
authors: Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington.
authors: Mary L
authors: ML
authors: Biggs
authors: National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
authors: Susan J
authors: SJ
authors: Zieman
authors: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors: Jorge R
authors: JR
authors: Kizer
authors: Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California; Divisions of Nephrology and Preventive Medicine, University of California-San Diego, San Diego, California.
authors: Joachim H
authors: JH
authors: Ix
authors: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Dariush
authors: D
authors: Mozaffarian
authors: Department of Pathology, Colchester Research Facility, University of Vermont, Colchester, Virginia.
authors: Russell P
authors: RP
authors: Tracy
authors: Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington; Department of Health Services, University of Washington, Seattle, Washington; Group Health Research Institute, Group Health Cooperative, Seattle, Washington.
authors: Bruce M
authors: BM
authors: Psaty
authors: Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington.
authors: David S
authors: DS
authors: Siscovick
authors: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors: Kenneth J
authors: KJ
authors: Mukamal
authors: Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Boston Veterans Affairs Healthcare System, Boston, Massachusetts.
authors: Luc
authors: L
authors: Djousse
mesh_terms: D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D002423:Cause of Death / Q000639:trends; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified