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

Abstract

BACKGROUND:

Some 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.

RESULTS:

Both 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.

CONCLUSIONS:

When 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).

• Authors: Harold Bays, Scott Conard, Lawrence A Leiter, Steven Bird, Erin Jensen, Mary E Hanson, Arvind Shah, Andrew M Tershakovec
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 9 Pg. 136 (Nov 30 2010) ISSN: 1476-511X [Electronic] England
• PMID: 21118495 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Azetidines
• Cholesterol, LDL
• Heptanoic Acids
• Pyrroles
• Atorvastatin
• Ezetimibe

Topics

• Aged
• Anticholesteremic Agents (therapeutic use)
• Atorvastatin
• Azetidines (therapeutic use)
• Cholesterol, LDL (blood)
• Coronary Artery Disease (blood, drug therapy)
• Ezetimibe
• Female
• Heptanoic Acids (therapeutic use)
• Humans
• Male
• Middle Aged
• Pyrroles (therapeutic use)