Plasma-free fatty acids, fatty acidebinding protein 4, and mortality in older adults (from the cardiovascular health study)

Michael D. Miedema, Marlena Maziarz, Mary L. Biggs, Susan J. Zieman, Jorge R. Kizer, Joachim H. Ix, Dariush Mozaffarian, Russell P. Tracy, Bruce M. Psaty, David S. Siscovick, Kenneth J. Mukamal, Luc Djousse

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated levels of FFA and fatty acidebinding 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 dosedependent 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.

Original languageEnglish (US)
Pages (from-to)843-848
Number of pages6
JournalAmerican Journal of Cardiology
Issue number6
StatePublished - Sep 15 2014
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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