Novel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study

Abstract

Background: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related 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 patterns 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 independent 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 associated 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 incidence 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 progression in women with IHD.

FIGURE 1.

Multivariable-adjusted associations of plasma phospholipid FA patterns with risk of CVD in the Cardiovascular Health Study (n = 2972). During the 32,265 person-years, 780 CVD events occurred (incident rate = 2417/100,000). Each panel shows results from 2 separate Cox proportional hazard models by using the restrictive cubic spline (solid line) or using quintile categories (◆); dotted lines and error bars represent 95% CIs. P values for linear associations are presented. None of the patterns showed significant nonlinear associations (P-nonlinearity > 0.05). Cox proportional hazard model was adjusted for sex, race (white or nonwhite), education (<high school, high school graduate, college graduate, or >college), smoking status (never, former, or current), exercise intensity (no exercise, low, moderate, or high), leisure-time physical activity (kcal/wk), 3-y weight change (kg), prevalent diabetes (yes or no), treated hypertension (yes or no), alcohol intake (tertile categories), total energy intake (kcal/d), and food consumptions (fish, high-fat dairy products, margarine, sweets, nuts, fried products, meats, and processed meats; servings/wk each). The 3 patterns were also mutually adjusted. Estimates were corrected for regression dilution bias and consequently strengthened from the estimates (see the main text) without the bias correction. CVD, cardiovascular disease; FA, fatty acid; LCMUFA, long-chain MUFA.