© 1997 American Heart Association, Inc.
Articles |
The Role of Triglyceride-Rich Lipoprotein Families in the Progression of Atherosclerotic Lesions as Determined by Sequential Coronary Angiography From a Controlled Clinical Trial
From the Lipid and Lipoprotein Laboratory, Oklahoma Medical Research Foundation (P.A., C.K.-G.), Oklahoma City, Oklahoma, and the Atherosclerosis Research Unit, Division of Cardiology, Departments of Medicine and Preventive Medicine (W.J.M., H.N.H.), University of Southern California, Los Angeles.
Correspondence to Howard N. Hodis, MD, Atherosclerosis Research Unit, Division of Cardiology, University of Southern California School of Medicine, 2250 Alcazar St, CSC 132, Los Angeles, CA 90033.
Abstract We have demonstrated previously in a subset of Monitored Atherosclerosis Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin significantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (apo) B–containing LpBc (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defined by their apolipoprotein composition. This differential effect of lovastatin on apoB-containing lipoprotein families offered the opportunity to determine in the same subset of MARS subjects the independent relationship of LpB and LpBc with the progression of coronary artery disease. Subjects randomized to either lovastatin (40 mg twice daily) or matching placebo were evaluated by coronary angiography before randomization and after 2 years of treatment, and the overall coronary status was judged by a coronary global change score. In the lovastatin-treated group, there were 22 nonprogressors (69%) and 10 progressors (31%), while in the placebo group 13 subjects (42%) were nonprogressors and 18 (58%) were progressors (P<.03). In the lovastatin-treated group, lipid and lipoprotein parameters did not differ between progressors and nonprogressors except for LpBc and LpA-II:B:C:D:E particle levels, which were statistically higher in progressors (P=.02). In the placebo-treated group, progressors differed from nonprogressors by having significantly higher levels of triglycerides (P=.03) and apoC-III in VLDL+LDL (P=.05), the characteristic constituents of triglyceride-rich lipoproteins. In the placebo- and lovastatin-treated groups combined, progressors had significantly higher on-trial levels of triglycerides (P=.003), VLDL cholesterol (P=.005), apoC-III in VLDL+LDL (P=.008), apoC-III (P=.01), apoB (P=.03), and total cholesterol (P=.04) than nonprogressors. Even after adjustment for treatment group, progressors in the combined placebo- and lovastatin-treated groups had significantly higher levels of LpBc, LpA-II:B:C:D:E, triglycerides, and apoC-III in VLDL+LDL than nonprogressors. Progressors in the placebo-treated, lovastatin-treated, and combined treatment groups had lower levels of LpA-I but not LpA-I:A-II than nonprogressors, and this difference reached statistical significance (P=.047) in the combined sample adjusted for treatment group. Results of this study show that elevated levels of triglyceride-rich LpBc in general and LpA-II:B:C:D:E in particular contribute significantly to the progression of coronary artery disease. Furthermore, they provide additional evidence for the potentially protective role of LpA-I particles in the atherogenic process and suggest that apolipoprotein-defined lipoprotein families may be more specific prognosticators of coronary artery atherosclerosis progression than lipids and apolipoproteins.
Key Words: atherosclerosis • apolipoproteins • clinical trials • lipoprotein particles
This article has been cited by other articles:
 |
|
 |
|
  H. Shimano ApoAII Controversy Still in Rabbit? Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 1984 - 1985. [Full Text] [PDF]
|
|
|
|
|
|
T. Koike, S. Kitajima, Y. Yu, Y. Li, K. Nishijima, E. Liu, H. Sun, A. B. Waqar, N. Shibata, T. Inoue, et al. Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia: A New Model for Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 2047 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Fruchart, F. M Sacks, M. P Hermans, G. Assmann, W V. Brown, R. Ceska, M J. Chapman, P. M Dodson, P. Fioretto, H. N Ginsberg, et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients Diabetes and Vascular Disease Research, November 1, 2008; 5(4): 319 - 335. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Kawakami, M. Osaka, M. Tani, H. Azuma, F. M. Sacks, K. Shimokado, and M. Yoshida Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction Circulation, August 12, 2008; 118(7): 731 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mallika, B. Goswami, and M. Rajappa Atherosclerosis Pathophysiology and the Role of Novel Risk Factors: A Clinicobiochemical Perspective Angiology, November 1, 2007; 58(5): 513 - 522. [Abstract] [PDF]
|
|
|
|
|
|
R. S. Birjmohun, G. M. Dallinga-Thie, J. A. Kuivenhoven, E. S.G. Stroes, J. D. Otvos, N. J. Wareham, R. Luben, J. J.P. Kastelein, K.-T. Khaw, and S. M. Boekholdt Apolipoprotein A-II Is Inversely Associated With Risk of Future Coronary Artery Disease Circulation, October 30, 2007; 116(18): 2029 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-J. Shin, P. J Blanche, R. S Rawlings, H. S Fernstrom, and R. M Krauss Increased plasma concentrations of lipoprotein(a) during a low-fat, high-carbohydrate diet are associated with increased plasma concentrations of apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins Am. J. Clinical Nutrition, June 1, 2007; 85(6): 1527 - 1532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zheng, C. Khoo, K. Ikewaki, and F. M. Sacks Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions J. Lipid Res., May 1, 2007; 48(5): 1190 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F Hilpert, S. G West, P. M Kris-Etherton, K. D Hecker, N. M Simpson, and P. Alaupovic Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes Am. J. Clinical Nutrition, February 1, 2007; 85(2): 369 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kawakami, M. Aikawa, P. Alcaide, F. W. Luscinskas, P. Libby, and F. M. Sacks Apolipoprotein CIII Induces Expression of Vascular Cell Adhesion Molecule-1 in Vascular Endothelial Cells and Increases Adhesion of Monocytic Cells Circulation, August 15, 2006; 114(7): 681 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kawakami, M. Aikawa, P. Libby, P. Alcaide, F. W. Luscinskas, and F. M. Sacks Apolipoprotein CIII in Apolipoprotein B Lipoproteins Enhances the Adhesion of Human Monocytic Cells to Endothelial Cells Circulation, February 7, 2006; 113(5): 691 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Park, P. G Jones, and W. S Harris Triacylglycerol-rich lipoprotein margination: a potential surrogate for whole-body lipoprotein lipase activity and effects of eicosapentaenoic and docosahexaenoic acids Am. J. Clinical Nutrition, July 1, 2004; 80(1): 45 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Carmena, P. Duriez, and J.-C. Fruchart Atherogenic Lipoprotein Particles in Atherosclerosis Circulation, June 15, 2004; 109(23_suppl_1): III-2 - III-7. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. M. Dallinga-Thie, I. I.L. Berk-Planken, A. H. Bootsma, and H. Jansen Atorvastatin Decreases Apolipoprotein C-III in Apolipoprotein B-Containing Lipoprotein and HDL in Type 2 Diabetes: A potential mechanism to lower plasma triglycerides Diabetes Care, June 1, 2004; 27(6): 1358 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Chiuve, L. A. Martin, H. Campos, and F. M. Sacks Effect of the Combination of Methyltestosterone and Esterified Estrogens Compared with Esterified Estrogens Alone on Apolipoprotein CIII and Other Apolipoproteins in Very Low Density, Low Density, and High Density Lipoproteins in Surgically Postmenopausal Women J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2207 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.J Chapman and M Caslake Non-high-density lipoprotein cholesterol as a risk factor: addressing risk associated with apolipoprotein B-containing lipoproteins Eur. Heart J. Suppl., March 1, 2004; 6(suppl_A): A43 - A48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Frohlich and M. Dobiasova Fractional Esterification Rate of Cholesterol and Ratio of Triglycerides to HDL-Cholesterol Are Powerful Predictors of Positive Findings on Coronary Angiography Clin. Chem., November 1, 2003; 49(11): 1873 - 1880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Lee, H. Campos, L. A. Moye, and F. M. Sacks LDL Containing Apolipoprotein CIII Is an Independent Risk Factor for Coronary Events in Diabetic Patients Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 853 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Park and W. S. Harris Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance J. Lipid Res., March 1, 2003; 44(3): 455 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text]
|
|
|
|
|
|
M. Guerin, P. Egger, W. Le Goff, C. Soudant, R. Dupuis, and M. J. Chapman Atorvastatin Reduces Postprandial Accumulation and Cholesteryl Ester Transfer Protein-Mediated Remodeling of Triglyceride-Rich Lipoprotein Subspecies in Type IIB Hyperlipidemia J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4991 - 5000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Blanco-Vaca, J. C. Escola-Gil, J. M. Martin-Campos, and J. Julve Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein J. Lipid Res., November 1, 2001; 42(11): 1727 - 1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. McGladdery and J. J. Frohlich Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy J. Lipid Res., November 1, 2001; 42(11): 1905 - 1912. [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]
|
|
|
|
 |
|
 Y. Park, W. J. Grellner, W. S. Harris, and J. M. Miles A new method for the study of chylomicron kinetics in vivo Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1258 - E1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Sacks, P. Alaupovic, L. A. Moye, T. G. Cole, B. Sussex, M. J. Stampfer, M. A. Pfeffer, and E. Braunwald VLDL, Apolipoproteins B, CIII, and E, and Risk of Recurrent Coronary Events in the Cholesterol and Recurrent Events (CARE) Trial Circulation, October 17, 2000; 102(16): 1886 - 1892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Escolà-Gil, J. Julve, A. Marzal-Casacuberta, J. Ordóñez-Llanos, F. González-Sastre, and F. Blanco-Vaca Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia J. Lipid Res., August 1, 2000; 41(8): 1328 - 1338. [Abstract] [Full Text]
|
|
|
|
|
|
S. M. Haffner Secondary Prevention of Coronary Heart Disease : The Role of Fibric Acids Circulation, July 4, 2000; 102(1): 2 - 4. [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Jacobson, G. G. Griffiths, C. Varas, D. Gause, J. C. Y. Sung, and C. M. Ballantyne Impact of Evidence-Based "Clinical Judgment" on the Number of American Adults Requiring Lipid-Lowering Therapy Based on Updated NHANES III Data Arch Intern Med, May 8, 2000; 160(9): 1361 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Clee, N. Bissada, F. Miao, L. Miao, A. D. Marais, H. E. Henderson, P. Steures, J. McManus, B. McManus, R. C. LeBoeuf, et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis J. Lipid Res., April 1, 2000; 41(4): 521 - 531. [Abstract] [Full Text]
|
|
|
|
|
|
R. van Antwerpen, M. La Belle, E. Navratilova, and R. M. Krauss Structural heterogeneity of apoB-containing serum lipoproteins visualized using cryo-electron microscopy J. Lipid Res., October 1, 1999; 40(10): 1827 - 1836. [Abstract] [Full Text]
|
|
|
|
|
|
J. S. Cohn, C. Marcoux, and J. Davignon Detection, Quantification, and Characterization of Potentially Atherogenic Triglyceride-Rich Remnant Lipoproteins Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2474 - 2486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Hodis Triglyceride-Rich Lipoprotein Remnant Particles and Risk of Atherosclerosis Circulation, June 8, 1999; 99(22): 2852 - 2854. [Full Text] [PDF]
|
|
|
|
|
|
C. Lee, F. Sigari, T. Segrado, S. Horkko, S. Hama, P. V. Subbaiah, M. Miwa, M. Navab, J. L. Witztum, and P. D. Reaven All ApoB-Containing Lipoproteins Induce Monocyte Chemotaxis and Adhesion When Minimally Modified : Modulation of Lipoprotein Bioactivity by Platelet-Activating Factor Acetylhydrolase Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1437 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Boisfer, G. Lambert, V. Atger, N. Q. Tran, D. Pastier, C. Benetollo, J.-F. Trottier, I. Beaucamps, M. Antonucci, M. Laplaud, et al. Overexpression of Human Apolipoprotein A-II in Mice Induces Hypertriglyceridemia Due to Defective Very Low Density Lipoprotein Hydrolysis J. Biol. Chem., April 23, 1999; 274(17): 11564 - 11572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ballantyne, J. A. Herd, L. L. Ferlic, J. K. Dunn, J. A. Farmer, P. H. Jones, J. R. Schein, and A. M. Gotto Jr Influence of Low HDL on Progression of Coronary Artery Disease and Response to Fluvastatin Therapy Circulation, February 16, 1999; 99(6): 736 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Leary, T. Wang, D. J. Baker, D. D. Cilla, J. Zhong, G. R. Warnick, K. Nakajima, and R. J. Havel Evaluation of an immunoseparation method for quantitative measurement of remnant-like particle-cholesterol in serum and plasma Clin. Chem., December 1, 1998; 44(12): 2490 - 2498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ruotolo, C.-G.o. Ericsson, C. Tettamanti, F. Karpe, L. Grip, B. Svane, J. Nilsson, U. de Faire, and A. Hamsten Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) J. Am. Coll. Cardiol., November 15, 1998; 32(6): 1648 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Syvanne, M. S. Nieminen, M. H. Frick, H. Kauma, S. Majahalme, V. Virtanen, Y. A. Kesaniemi, A. Pasternack, C. Ehnholm, and M.-R. Taskinen Associations Between Lipoproteins and the Progression of Coronary and Vein-Graft Atherosclerosis in a Controlled Trial With Gemfibrozil in Men With Low Baseline Levels of HDL Cholesterol Circulation, November 10, 1998; 98(19): 1993 - 1999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gotto Jr Triglyceride : The Forgotten Risk Factor Circulation, March 24, 1998; 97(11): 1027 - 1028. [Full Text] [PDF]
|
|