Abstract
ObjectiveTest whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses.MethodsGradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments.ResultsThe change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2–24.6 nm) and LDL-IVa (23.3–24.1 nm) before (both P = 0.002) and after (P = 0.01 and P = 0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (P = 0.01) and after (P = 0.03) adjustment for treatment group and the standard lipid values.ConclusionsPlasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol.Trial RegistrationClinicalTrials.gov NCT00000553
Highlights
The HDL-Atherosclerosis Treatment Study (HATS) was a double-blind randomized controlled clinical trial of simvastatin plus niacin and/or a mixture of antioxidants in 160 patients selected for clinical coronary disease with at least 3 stenoses of at least 30 percent of the luminal diameter or 1 stenosis of at least 50 percent, and low high-density lipoprotein (HDL)-cholesterol [1]
The technique of non-denaturing gradient gel electrophoresis was first used to identify seven distinct size subclasses of low-density lipoprotein (LDL) particles [2], and has subsequently been adapted to provide a measure of the plasma concentration of cholesterol in each of these subclasses [5]. This method was employed in HATS to assess whether coronary atherosclerosis progression and clinical endpoints in HATS could be attributed to on-study plasma levels of specific LDL subclasses
One subject assigned to antioxidants, one assigned to simvastatin-niacin antioxidants, and two subjects assigned to placebo were missing either gradient gel (2 subjects) or vertical spin LDL-cholesterol (2 subjects), leaving placebo treated, simvastatin-niacin, antioxidant, and simvastatin-niacin & antioxidant treated participants for study
Summary
The HDL-Atherosclerosis Treatment Study (HATS) was a double-blind randomized controlled clinical trial of simvastatin plus niacin and/or a mixture of antioxidants in 160 patients selected for clinical coronary disease with at least 3 stenoses of at least 30 percent of the luminal diameter or 1 stenosis of at least 50 percent, and low high-density lipoprotein (HDL)-cholesterol [1]. The study demonstrated that simvastatin plus niacin treatment reduced the rate of progression of angiographically-documented coronary artery stenoses relative to placebo treatment, and reduced the frequency of clinical endpoints (3 percent) relative to placebo (24 percent). This method was employed in HATS to assess whether coronary atherosclerosis progression and clinical endpoints in HATS could be attributed to on-study plasma levels of specific LDL subclasses
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