Circulating Very-Long Chain Saturated Fatty Acids and Incident Coronary Heart Disease in U.S. Men and Women
Background—Circulating very-long chain saturated fatty acids (VLCSFAs) may play an active role in the etiology of cardiometabolic diseases.
Methods and Results—We measured three 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 Nurses' Health Study (NHS; 1990-2006) and among men in Health Professionals Follow-up Study (HPFS; 1994-2008). A total of 1233 CHD-free controls were randomly selected and matched to cases in these two cohorts. Conditional logistic regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). Plasma VLCSFAs were correlated with favorable profiles of blood lipids, C-reactive protein, and adiponectin in the NHS and HPFS, as well as with fasting insulin and C-peptide levels in a nationally-representative U.S. comparison population. After multivariate adjustment for lifestyle factors, body mass index (BMI), diet, and long-chain n-3 and trans fatty acids, total VLCSFAs in plasma was associated with a 52% decreased risk of CHD [pooled HR (95% CI); 0.48 (0.32, 0.72), comparing extreme quintiles; Ptrend<0.0001]. For VLCSFAs in erythrocytes, a non-significant inverse trend with CHD risk was observed [pooled HR (95% CI); 0.66 (0.41, 1.06), comparing extreme quintiles; Ptrend=0.16].
Conclusions—In U.S. men and women, plasma VLCSFAs were independently associated with favorable profiles of blood lipids and other CVD risk markers and a lower risk of CHD. Erythrocyte VLCSFAs were associated with non-significant trends of lower CHD risk. Future studies are warranted to elucidate underlying biological mechanisms.
- Received December 15, 2014.
- Revision received May 18, 2015.
- Accepted May 27, 2015.