Non-Esterified Fatty Acid Profiles and Cause-Specific Mortality: The Cardiovascular Health Study.

Context: Total fasting non-esterified fatty acid (NEFA) levels have been associated with mortality. The corresponding associations with NEFA levels following an oral glucose tolerance test (OGTT) and with individual fasting NEFA species are unclear.

Objective: We evaluated the associations of post-load NEFA, fasting subclasses and individual NEFA with mortality.

Methods: The Cardiovascular Health Study is a population-based cohort study of community-dwelling adults over 64 years of age from 4 US communities that began in 1989-1990. Participants had total NEFA measured enzymatically before and 2 hours after an OGTT from archived serum samples collected in 1996-1997. Fasting individual NEFA were also measured using gas chromatography. Cox proportional hazard models were used to evaluate adjusted hazard ratios (aHR) for mortality associated with fasting and post-load total NEFA, and fasting individual and fatty acid subclasses (saturated, monounsaturated, n-3 and n-6 polyunsaturated, and trans).

Results: The final population included 1996 participants (mean age 78 years; 60.5% female). Over a median 11-year follow-up period, 1678 participants died. Total fasting NEFA was associated with higher risk of all-cause mortality (aHR per SD: 1.17, 95% CI [1.10-1.23]). Total post-load NEFA was not associated with mortality. Among subclasses, only monounsaturated fatty acid (MUFA) was associated with total mortality (aHR 1.24, 95% CI [1.09-1.41]). For individual NEFAs, nervonic acid (aHR 1.06, 95% CI [1.01-1.12]), petroselaidic acid (aHR 1.21, 95% CI [1.03-1.42]), and eicosapentaenoic acid (aHR 0.90, 95% CI [0.82-0.99]) were associated with all-cause mortality.

Conclusion: Individual fasting NEFAs represent attractive candidates for medical and public health interventions aimed at improving survivorship in older adults and should be investigated further.