EFFECTS OF LOWERING AVERAGE OR BELOW-AVERAGE CHOLESTEROL LEVELS ON THE PROGRESSION OF CAROTID ATHEROSCLEROSIS - RESULTS OF THE LIPID ATHEROSCLEROSIS SUBSTUDY

Background-Cholesterol lowering in patients with above-average cholest erol levels has been shown to reduce the progression of atherosclerosi s and lower the risk of coronary heart disease events. However, there has been uncertainty about the effects of cholesterol lowering in pati ents with average or below-average cholesterol levels. Methods and Res ults-ln this study, 522 patients with a history of myocardial infarcti on or unstable angina and with baseline levels of total cholesterol be tween 4 and 7 mmol/L (mean, 5.7 mmol/L) were randomized to treatment w ith a low fat diet plus pravastatin (40 mg daily) or to a low fat diet plus placebo. Treatment with pravastatin reduced the levels of total cholesterol by 19%, LDL cholesterol by 27%, apolipoprotein B by 19%, a nd triglycerides by 13% tall 2P<.0001) and increased apolipoprotein Al and HDL cholesterol levels by 4% (both 2P<.0005), in comparison with placebo. Carotid atherosclerosis was assessed from B-mode ultrasound m easurements of the common carotid artery. After 4 years, mean carotid wall thickness had increased by 0.048 mm (SE=0.01) in the placebo grou p and declined by 0.014 mm in the pravastatin-treated group (SE=0.01) (2P for difference <.0001). The effect of treatment on wall thickness was similar in three groups classified by tertiles of total cholestero l at baseline, with mean levels of 4.8, 5.7, and 6.6 mmol/L, respectiv ely (2P for interaction >.8). Conclusions-Treatment with pravastatin r educed the development of carotid atherosclerosis among patients with coronary heart disease and a wide range of pretreatment cholesterol le vels. Treatment with this agent prevented any detectable increase in c arotid wall thickening over 4 years of follow-up.