(P22-045-20) Serum Non-esterified Fatty Acids and Risk of Incident Stroke in Older Adults: The Cardiovascular Health Study

Objectives: Significant associations between plasma total non-esterified fatty acid (NEFA) concentrations and incident ischemic stroke have been reported in some but not all prospective cohort studies. Given the functional and structural diversity among circulating NEFA, the association of individual or sub-groups of circulating NEFAs may provide additional insight into their relationship with incident stroke. We hypothesized fasting serum monounsaturated, n-6 polyunsaturated (PUFA) and n-3 PUFA NEFA are inversely associated, and saturated and trans NEFA are positively associated with incident stroke.

Methods: We analyzed the incidence of stroke among Cardiovascular Health Study (CHS) participants who were free of stroke in 1996-1997 (baseline) and had an archived fasting serum sample (N=2028). At baseline, mean age was 77.8±4.5, body mass index (BMI) was 26.7±4.4 and 61% were female. A total of 38 individual NEFAs were measured using gas chromatography. Cox regression was used to evaluate the association of individual and 5 sub-group (saturated, monounsaturated, n-6 PUFA, n-3 PUFA and trans) NEFAs with incident stroke, adjusting for age, sex, race and field center (model 1); model 1 covariates plus serum albumin, smoking, education, physical activity, alcohol consumption, eGFR, BMI, aspirin use, waist circumference, hypertension, prevalent diabetes and total serum cholesterol concentration (model 2).

Results: A total of 338 cases of incident stroke occurred during median follow-up of 10.5 years. In the fully adjusted model 2, individuals in the highest quartile of serum 16:1n-7 had a 56% higher risk of stroke (quartiles 4 versus 1, hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.08-2.25; P-trend=0.02); highest quartile of total n-6 PUFA NEFA had a 40% higher risk (HR, 1.40; 95% CI, 0.99-1.98; P-trend=0.03); and highest quartile of  20:3n-6 had a 53% higher risk (HR, 1.53; 95% CI, 1.09-2.14; P-trend=0.01). No significant associations were observed between saturated, n-3 PUFA, and trans NEFAs with incident stroke.

Conclusions: These data suggest a positive association between fasting serum 16:1n-7, 20:3n-6 and total n-6 PUFA NEFAs with incident stroke in CHS participants. No significant associations were observed for the other individual or sub-groups of NEFAs.

Funding Sources: NIH and USDA