on March 13, 2006
Published online before print March 13, 2006, doi: 10.1161/CIRCULATIONAHA.105.565135
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 27, 2005
From LipoScience, Inc, Raleigh, NC (J.D.O., I.S.); Veterans Affairs Medical Center Cooperative Studies Program Coordinating Center, West Haven, Conn (D.C.); Division of Nutrition, Centers for Disease Control and Prevention, Atlanta, Ga (D.S.F.); Lipid Research Laboratory, Tufts University School of Medicine, Boston, Mass (E.J.S., J.R.M.); Center for Chronic Disease Outcomes Research, Veterans Affairs Medical Center, Minneapolis, Minn (H.E.B.); and Boston University School of Medicine, Boston, Mass (S.J.R.). * To whom correspondence should be addressed. E-mail: sjrobins{at}bu.edu.
Background--Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. Methods and Results--This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (-5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events. Conclusions--The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.
Revised on December 5, 2005
Accepted on January 13, 2006
Low-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial
James D. Otvos PhD,
Key words: coronary disease • drugs • lipoproteins • risk factors • spectroscopy
This article has been cited by other articles:
 |
|
 |
|
  S. J. Robins, D. Collins, J. J. Nelson, H. E. Bloomfield, and B. F. Asztalos Cardiovascular Events With Increased Lipoprotein-Associated Phospholipase A2 and Low High-Density Lipoprotein-Cholesterol: The Veterans Affairs HDL Intervention Trial Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1172 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Movva and D. J. Rader Laboratory Assessment of HDL Heterogeneity and Function Clin. Chem., May 1, 2008; 54(5): 788 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, and J. L. Witztum Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus Conference Report From the American Diabetes Association and the American College of Cardiology Foundation J. Am. Coll. Cardiol., April 15, 2008; 51(15): 1512 - 1524. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kaess, M. Fischer, A. Baessler, K. Stark, F. Huber, W. Kremer, H. R. Kalbitzer, H. Schunkert, G. Riegger, and C. Hengstenberg The lipoprotein subfraction profile: heritability and identification of quantitative trait loci J. Lipid Res., April 1, 2008; 49(4): 715 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, and J. L. Witztum Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation Diabetes Care, April 1, 2008; 31(4): 811 - 822. [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Andon and J. W. Anderson State of the Art Reviews: The Oatmeal-Cholesterol Connection: 10 Years Later American Journal of Lifestyle Medicine, February 1, 2008; 2(1): 51 - 57. [Abstract] [PDF]
|
|
|
|
 |
|
 I. H. de Boer, B. C. Astor, H. Kramer, W. Palmas, S. L. Seliger, M. G. Shlipak, D. S. Siscovick, M. Y. Tsai, and B. Kestenbaum Lipoprotein Abnormalities Associated with Mild Impairment of Kidney Function in the Multi-Ethnic Study of Atherosclerosis Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 125 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. Mudd, B. A. Borlaug, P. V. Johnston, B. G. Kral, R. Rouf, R. S. Blumenthal, and P. O. Kwiterovich Jr Beyond Low-Density Lipoprotein Cholesterol: Defining the Role of Low-Density Lipoprotein Heterogeneity in Coronary Artery Disease J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1735 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dasgupta, A. Roy, M. Jana, D. M. Hartley, and K. Pahan Gemfibrozil Ameliorates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Independent of Peroxisome Proliferator-Activated Receptor-{alpha} Mol. Pharmacol., October 1, 2007; 72(4): 934 - 946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Deeg, J. B. Buse, R. B. Goldberg, D. M. Kendall, A. J. Zagar, S. J. Jacober, M. A. Khan, A. T. Perez, M. H. Tan, and on behalf of the GLAI Study Investigators Pioglitazone and Rosiglitazone Have Different Effects on Serum Lipoprotein Particle Concentrations and Sizes in Patients With Type 2 Diabetes and Dyslipidemia Diabetes Care, October 1, 2007; 30(10): 2458 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Lincoff, K. Wolski, S. J. Nicholls, and S. E. Nissen Pioglitazone and Risk of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Trials JAMA, September 12, 2007; 298(10): 1180 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S Kelley, D. Siegel, M. Vemuri, and B. E Mackey Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men Am. J. Clinical Nutrition, August 1, 2007; 86(2): 324 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Rosenson, D. A. Wolff, A. L. Huskin, I. B. Helenowski, and A. W. Rademaker Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome Diabetes Care, August 1, 2007; 30(8): 1945 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Mukamal, R. H. Mackey, L. H. Kuller, R. P. Tracy, R. A. Kronmal, M. A. Mittleman, and D. S. Siscovick Alcohol Consumption and Lipoprotein Subclasses in Older Adults J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2559 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pozzi, M. R. Ibanez, A. E. Gatica, S. Yang, S. Wei, S. Mei, J. R. Falck, and J. H. Capdevila Peroxisomal Proliferator-activated Receptor-{alpha}-dependent Inhibition of Endothelial Cell Proliferation and Tumorigenesis J. Biol. Chem., June 15, 2007; 282(24): 17685 - 17695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Q. Lai, D. K. Arnett, D. Corella, R. J. Straka, M. Y. Tsai, J. M. Peacock, X. Adiconis, L. D. Parnell, J. E. Hixson, M. A. Province, et al. Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants: The GOLDN Study Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1417 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Nicholls, E. M. Tuzcu, I. Sipahi, A. W. Grasso, P. Schoenhagen, T. Hu, K. Wolski, T. Crowe, M. Y. Desai, S. L. Hazen, et al. Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis JAMA, February 7, 2007; 297(5): 499 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Roberts, C. Ng, S. Hama, A. J. Eliseo, and R. J. Barnard Effect of a short-term diet and exercise intervention on inflammatory/anti-inflammatory properties of HDL in overweight/obese men with cardiovascular risk factors J Appl Physiol, December 1, 2006; 101(6): 1727 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Harper, M. C. Edwards, and T. A. Jacobson Flaxseed Oil Supplementation Does Not Affect Plasma Lipoprotein Concentration or Particle Size in Human Subjects J. Nutr., November 1, 2006; 136(11): 2844 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Barter and K.-A. Rye Cardioprotective Properties of Fibrates: Which Fibrate, Which Patients, What Mechanism? Circulation, March 28, 2006; 113(12): 1553 - 1555. [Full Text] [PDF]
|
|