on March 13, 2003
Published online before print March 13, 2003, doi: 10.1161/01.ATV.0000066131.01313.EB
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Submitted on February 5, 2003
Accepted on February 26, 2003
LDL Particles Containing Apolipoprotein CIII Are Independent Risk Factors for Coronary Events in Diabetic Patients
Sung-Joon Lee ;
From the Department of Nutrition, Harvard School of Public Health (S.J.L., H.C., F.M.S.) and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital (F.M.S.), Boston, Mass, and University of Texas School of Public Health (L.A.M.), Houston, Tex. Dr Lee is presently at the Stanford School of Medicine, Calif.
* To whom correspondence should be addressed. E-mail: fsacks{at}hsph.harvard.edu.
Objective--Triglyceride-rich lipoproteins that contain apolipoprotein CIII (apoCIII) are prominent in diabetic dyslipidemia. We hypothesized that these lipoproteins increase coronary disease risk in diabetic patients beyond that caused by standard lipid risk factors.
Methods and Results--Diabetic patients with previous myocardial infarction were followed for 5 years, and 121 who had a recurrent coronary event were matched to 121 who did not. VLDL and LDL that contained or did not contain apoCIII (CIII+ or CIII-) were prepared by immunoaffinity chromatography and ultracentrifugation. IDL was included in the LDL fraction. LDL CIII+, rich in cholesterol and triglyceride, was the strongest predictor of coronary events (relative risk [RR] 6.6, P<0.0001, for 4th versus 1st quartile). LDL CIII+ comprised 10% of total LDL. The main type of LDL, LDL CIII-, was less strongly predictive (RR 2.2, P=0.07). The increased risk associated with LDL CIII+ was unaffected by adjustment for plasma lipids, apoB, non-HDL cholesterol, or the other VLDL and LDL types. For VLDL CIII+, RR 0.5, P=0.07; for VLDL CIII-, RR 2.3, P=0.046. The presence of apolipoprotein E with CIII on VLDL and LDL did not affect risk.
Conclusions--LDL with apoCIII strongly predicts coronary events in diabetic patients independently of other lipids and may be an atherogenic remnant of triglyceride-rich VLDL metabolism.
Key words: apolipoprotein CIII • lipoproteins • coronary heart disease • apolipoprotein E • apolipoprotein B
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