Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women

Abstract

Background: Circulating very-long-chain saturated fatty acids (VLCSFAs) may play an active role in the origin of cardiometabolic diseases.

Methods and results: We measured 3 VLCSFAs (C20:0, C22:0, and C24:0) in plasma and erythrocytes using gas-liquid chromatography among 794 incident coronary heart disease (CHD) cases who were prospectively identified and confirmed among women in the Nurses' Health Study (NHS; 1990-2006) and among men in the Health Professionals Follow-Up Study (HPFS; 1994-2008). A total of 1233 CHD-free controls were randomly selected and matched to cases in these 2 cohorts. Conditional logistic regression was used to estimate hazard ratios and 95% confidence intervals. Plasma VLCSFAs were correlated with favorable profiles of blood lipids, C-reactive protein, and adiponectin in the NHS and HPFS and with fasting insulin and C-peptide levels in a nationally representative US comparison population. After multivariate adjustment for lifestyle factors, body mass index, diet, and long-chain n-3 and trans fatty acids, total VLCSFAs in plasma were associated with a 52% decreased risk of CHD (pooled hazard ratio, 0.48; 95% confidence interval, 0.32-0.72, comparing extreme quintiles; Ptrend<0.0001). For VLCSFAs in erythrocytes, a nonsignificant inverse trend with CHD risk was observed (pooled hazard ratio, 0.66; 95% confidence interval, 0.41-1.06, comparing extreme quintiles; Ptrend=0.16).

Conclusions: In US men and women, plasma VLCSFAs were independently associated with favorable profiles of blood lipids and other cardiovascular disease risk markers and a lower risk of CHD. Erythrocyte VLCSFAs were associated with nonsignificant trends of lower CHD risk. Future studies are warranted to elucidate the underlying biological mechanisms.

Keywords: coronary disease; fatty acids.

© 2015 American Heart Association, Inc.

Figures

Figure 1

Hazard ratio of coronary heart disease (95% CI) by plasma levels of total very-long chain saturated fatty acids in US men and women. Study participants with the highest 1% of fatty acid levels were excluded to minimize potential impact of outliers. Multivariate conditional logistic regression models were adjusted for the same set of covariates listed in the footnote to Table 3. The green solid line represents HRs and shaded areas represent the 95% CIs. The horizontal line is the reference and vertical lines represent the cut-off points for making quintiles. A, plasma; B, erythrocytes.

Figure 1

Hazard ratio of coronary heart disease (95% CI) by plasma levels of total very-long chain saturated fatty acids in US men and women. Study participants with the highest 1% of fatty acid levels were excluded to minimize potential impact of outliers. Multivariate conditional logistic regression models were adjusted for the same set of covariates listed in the footnote to Table 3. The green solid line represents HRs and shaded areas represent the 95% CIs. The horizontal line is the reference and vertical lines represent the cut-off points for making quintiles. A, plasma; B, erythrocytes.