Abstract
Background: Circulating fatty acids (FA) reflect complex interrelations of diet and metabolism. Few studies have evaluated circulating FA as patterns related to cardiovascular diseases (CVD). Methods: We applied principal component analysis (PCA) to 39 plasma phospholipid FA measured in 2,972 older adults (mean age=72.1) at baseline (1992) in the Cardiovascular Health Study, and derived FA patterns. We evaluated prospective associations of identified FA patterns with 14-year incidence of CVD, adjudicated by centralized committee, using multivariate Cox proportional hazards corrected for regression dilution bias. The CHS-derived FA patterns were evaluated in a separate cohort for associations with angiographically-defined atherosclerosis progression over 3.5 years in 1,912 coronary segments of 228 postmenopausal women (mean age=65.4) with established CHD, including FA in phospholipids, triglycerides, and cholesteryl esters. Results: Three distinct patterns were identified, that we characterized as having higher trans FA (TFA pattern), de novo lipogenesis FA (DNL pattern), and dairy and long-chain monounsaturated FA (dairy-LCMUFA pattern). During 32,265 person-years, 780 CVD events occurred, including 512 CHD and 346 stroke. The TFA pattern was associated with higher CVD risk (HR for quintiles 5 vs. 1=2.47 [95% CI 1.35–4.51]; p trend=0.006) (Figure), primarily due to stroke (HR=4.68 [1.85–11.8]; p trend=0.003) but not CHD (HR=1.08 [0.50–2.32]; p trend=0.6). The DNL and dairy-LCMUFA patterns were not associated with CVD, or with CHD or stroke examined separately (p>0.1). In the second cohort, the TFA pattern, but not the other 2 patterns, in all lipid compartments was positively associated with progression of coronary stenosis (p trend<0.05). Conclusions: Our results suggest PCA can derive informative FA patterns for assessing disease risk. A pattern mainly reflecting higher trans FA levels is linked to higher risk of stroke in older adults, and coronary stenosis progression in women with CHD.
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