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Change in alpha1 HDL concentration predicts progression in coronary artery stenosis
Bela F Asztalos1, Marcelo Batista, Katalin V Horvath
1Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Center on Aging at Tufts University and Division of Endocrinology, Metabolism, Diabetes, and Molecular Medicine, New England Medical Center, Boston, Mass 02111, USA. bela.asztalos@tufts.edu
Insights
Simvastatin-niacin therapy increased large HDL particles (alpha1), which was linked to reduced coronary artery stenosis progression over three years.
Area of Science:
- Cardiology
- Lipidology
- Pharmacology
Background:
- High-density lipoprotein (HDL) subpopulations play a role in reverse cholesterol transport.
- Alterations in HDL particle size and concentration are associated with cardiovascular disease risk.
Purpose of the Study:
- To investigate the impact of simvastatin-niacin and antioxidant vitamins on HDL subpopulations.
- To assess the relationship between changes in HDL subpopulations and coronary artery stenosis progression.
Main Methods:
- 123 subjects were randomized into four groups: simvastatin-niacin, simvastatin-niacin with antioxidant vitamins, antioxidant vitamins alone, and placebo.
- HDL subpopulations and coronary artery stenosis (via angiography) were measured over a 3-year treatment period.
Main Results:
- Simvastatin-niacin significantly increased large HDL particles (alpha1 and prealpha1) and decreased small particles (prebeta1 and alpha3).
- Adding antioxidant vitamins diminished these effects.
- Increased alpha1 HDL particle concentration correlated with reduced coronary artery stenosis progression.
Conclusions:
- Simvastatin-niacin therapy effectively increases large apoA-I-containing alpha1 HDL particles.
- The increase in alpha1 HDL particles is significantly associated with less coronary stenosis progression, independent of traditional risk factors.
Objective:
We examined the effects of simvastatin-niacin and antioxidant vitamins on changes in high-density lipoprotein (HDL) subpopulations and alterations in coronary artery stenosis, as assessed by angiography.
Methods And Results:
Lipids, lipoproteins, and HDL particles were measured on and off treatment in 123 subjects of the HDL-Atherosclerosis Treatment Study. Patients were assigned to 4 treatment groups, simvastatin-niacin, simvastatin-niacin-antioxidant vitamins, antioxidant vitamins, and placebo. Subjects were followed for 3 years on treatment and then for 2 months off treatment. Simvastatin-niacin significantly increased the 2 large apoA-I-containing HDL subpopulations, alpha1 and prealpha1, and significantly decreased the 2 smallest particles, prebeta1 and alpha3, compared with values obtained from the same patients off treatment. Adding antioxidant vitamins to the lipid-modifying agents blunted these effects (not significant). A significant negative correlation (r=-0.235; P<0.01) between the changes in alpha1 HDL particle concentration and coronary artery stenosis was noted. Subjects in the third tertile (157% increase in alpha1) had no progression of stenosis in the 3-year follow-up period, whereas subjects in the first tertile (15% decrease in alpha1) had an average of 2.1% increase in stenosis.
Conclusions:
Simvastatin-niacin therapy significantly increased the large apoA-I-containing alpha1 HDL particles. This increase was significantly associated with less progression of coronary stenosis even after adjusting for traditional risk factors.