(Circulation. 2000;102:1886.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Department of Nutrition, Harvard School of Public Health, Boston, Mass (F.M.S., M.J.S.); the Department of Medicine, Harvard Medical School and Brigham and Womens Hospital, Boston, Mass (F.M.S., M.J.S., M.A.P., E.B.); Oklahoma Medical Research Foundation, Oklahoma City (P.A.); University of Texas School of Public Health, Houston (L.A.M.); Washington University School of Medicine, St Louis, Mo (T.G.C.); and Memorial University of Newfoundland, St John, Newfoundland, Canada (B.S.).
Correspondence to Frank M. Sacks, MD, Nutrition Department, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu
BackgroundPlasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma.
Methods and ResultsWe conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDLapolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P=0.04), apoCIII in VLDL+LDL (RR 2.3, P=0.04), and apoE in HDL (RR 1.8, P=0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P=0.03), was not related to coronary events (RR 1.3, P=0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results.
ConclusionsThe plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.
Key Words: coronary disease apolipoproteins lipoproteins cholesterol
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||||
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||||
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||||
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References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text] |
||||
![]() |
K. Olin-Lewis, R. M. Krauss, M. La Belle, P. J. Blanche, P. H. R. Barrett, T. N. Wight, and A. Chait ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan J. Lipid Res., November 1, 2002; 43(11): 1969 - 1977. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. N. Ginsberg New Perspectives on Atherogenesis: Role of Abnormal Triglyceride-Rich Lipoprotein Metabolism Circulation, October 15, 2002; 106(16): 2137 - 2142. [Full Text] [PDF] |
||||
![]() |
K. K. Berneis and R. M. Krauss Metabolic origins and clinical significance of LDL heterogeneity J. Lipid Res., September 1, 2002; 43(9): 1363 - 1379. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Olivieri, C. Stranieri, A. Bassi, B. Zaia, D. Girelli, F. Pizzolo, E. Trabetti, S. Cheng, M. A. Grow, P. F. Pignatti, et al. ApoC-III gene polymorphisms and risk of coronary artery disease J. Lipid Res., September 1, 2002; 43(9): 1450 - 1457. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Olin-Lewis, J. L. Benton, J. C. Rutledge, D. G. Baskin, T. N. Wight, and A. Chait Apolipoprotein E Mediates the Retention of High-Density Lipoproteins by Mouse Carotid Arteries and Cultured Arterial Smooth Muscle Cell Extracellular Matrices Circ. Res., June 28, 2002; 90(12): 1333 - 1339. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. A. Kreisberg and A. Oberman Lipids and Atherosclerosis: Lessons Learned from Randomized Controlled Trials of Lipid Lowering and Other Relevant Studies J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 423 - 437. [Full Text] [PDF] |
||||
![]() |
D. C. Chan, G. F. Watts, P. H. Barrett, J. C.L. Mamo, and T. G. Redgrave Markers of Triglyceride-rich Lipoprotein Remnant Metabolism in Visceral Obesity Clin. Chem., February 1, 2002; 48(2): 278 - 283. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Frohlich, A. Sniderman, and R. H. Eckel Familial Combined Hyperlipidemia and Insulin Resistance Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 2100 - 2101. [Full Text] [PDF] |
||||
![]() |
H. Campos, L. A. Moye, S. P. Glasser, M. J. Stampfer, and F. M. Sacks Low-Density Lipoprotein Size, Pravastatin Treatment, and Coronary Events JAMA, September 26, 2001; 286(12): 1468 - 1474. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Tomiyasu, B. W. Walsh, K. Ikewaki, H. Judge, and F. M. Sacks Differential Metabolism of Human VLDL According to Content of ApoE and ApoC-III Arterioscler Thromb Vasc Biol, September 1, 2001; 21(9): 1494 - 1500. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Campos, D. Perlov, C. Khoo, and F. M. Sacks Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia J. Lipid Res., August 1, 2001; 42(8): 1239 - 1249. [Abstract] [Full Text] [PDF] |
||||
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