Vasanti S Malik1, Stephanie E Chiuve1, Hannia Campos1, Eric B Rimm1, Dariush Mozaffarian1, Frank B Hu1, Qi Sun2. 1. From Departments of Nutrition (V.S.M., S.E.C., H.C., E.B.R., F.B.H., Q.S.) and Epidemiology (E.B.R., D.M., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.); and Division of Preventive Medicine (S.E.C.), Division of Cardiovascular Medicine (D.M.), and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 2. From Departments of Nutrition (V.S.M., S.E.C., H.C., E.B.R., F.B.H., Q.S.) and Epidemiology (E.B.R., D.M., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.); and Division of Preventive Medicine (S.E.C.), Division of Cardiovascular Medicine (D.M.), and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. qisun@hsph.harvard.edu.
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.
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.
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