Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

Lipids in Health and Disease

Research

Lawrence A Leiter¹  Harold Bays²  Scott Conard³  Steven Bird⁴  Erin Jensen⁴  Andrew M Tershakovec⁴  Arvind Shah⁴  Mary E Hanson⁴ 

[1] Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital and the University of Toronto, Toronto, ON, Canada;Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA;Medical Edge Healthcare Group, P.A., Dallas, TX, USA;Merck, Sharp & Dohme Corp., a div. of Merck & Co., Inc., Whitehouse Station, NJ, USA;

关键词: Atorvastatin;    Ezetimibe;    Lipoprotein Subclass;    Lipoprotein Particle Size;    Baseline Triglyceride Level;   

DOI  :  10.1186/1476-511X-9-136

 received in 2010-10-26, accepted in 2010-11-30,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSome patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL.ResultsBoth treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL.ConclusionsWhen assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels.Trial Registration(Registered at clinicaltrials.gov: Clinical trial # NCT00276484)

【 授权许可】

CC BY   
© Bays et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.