Novel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study1–3

Background: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns re-lated to cardiovascular disease (CVD) risk. Objectives: We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived pat-terns to atherosclerosis progression in another independent cohort. Design: We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another indepen-dent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis. Results: Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was as-sociated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95 % CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95 % CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD in-cidence or with IHD or stroke (P-trend. 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend, 0.05). Conclusions: PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis pro-gression in women with IHD. Am J Clin Nutr doi: 10.3945/ajcn. 112.039990