The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol hydrochloride and niacin therapy in 162 nonsmoking men aged 40 to 59 years with previous coronary bypass surgery. During two years of treatment there was a 26% reduction in total plasma cholesterol, a 43% reduction in low-density lipoprotein cholesterol, plus a simultaneous 37% elevation of high-density lipoprotein cholesterol. This resulted in a significant reduction in the average number of lesions per subject that progressed (P less than .03) and the percentage of subjects with new atheroma formation (P less than .03) in native coronary arteries. Also, the percentage of subjects with new lesions (P less than .04) or any adverse change in bypass grafts (P less than .03) was significantly reduced. Deterioration in overall coronary status was significantly less in drug-treated subjects than placebo-treated subjects (P less than .001). Atherosclerosis regression, as indicated by perceptible improvement in overall coronary status, occurred in 16.2% of colestipol-niacin treated vs 2.4% placebo treated (P = .002).

T his report is a concise review of current knowledge of the structure and function of the intima of the aorta and the major distributing arteries. The main purpose of the review is to delineate normal arterial intima from atherosclerotic lesions and, in particular, to distinguish physiological adaptations from atherosclerotic increases in intimal thickness. To characterize normal intima, including the adaptive intimal thickenings, some of which represent locations in which atherosclerotic lesions are prone to develop, the structure, composition, and functions of the arterial intima in young people as well as in laboratory animals not subjected to known atherogenic stimuli are reviewed.This report on arterial intima is the first in a series of four. The second report will review and define initial, fatty streak, and intermediate types of atherosclerotic lesions, and the third report will review all types of advanced (i.e., potentially clinical and clinical) lesions. The overall objective is to define arterial intima and all types of atherosclerotic lesions, and then to postulate, in a fourth and final report, a valid and up-to-date pathobiological nomenclature and classification of atherosclerotic lesions.

his report is a concise review of current knowledge of the structure and function of the intima of the aorta and the major distributing arteries. The main purpose of the review is to delineate normal arterial intima from atherosclerotic lesions and, in particular, to distinguish physiological adaptations from atherosclerotic increases in intimal thickness. To characterize normal intima, including the adaptive intimal thickenings, some of which represent locations in which atherosclerotic lesions are prone to develop, the structure, composition, and functions of the arterial intima in young people as well as in laboratory animals not subjected to known atherogenic stimuli are reviewed.This report on arterial intima is the first in a series of four. The second report will review and define initial, fatty streak, and intermediate types of atherosclerotic lesions, and the third report will review all types of advanced (i.e., potentially clinical and clinical) lesions. The overall objective is to define arterial intima and all types of atherosclerotic lesions, and then to postulate, in a fourth and final report, a valid and up-to-date pathobiologicaJ nomenclature and classification of atherosclerotic lesions.

Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease-total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure-had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug-and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-IlI in high density lipoproteins of drug-treated subjects. Both drug-and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis. (Circulation 1990;81:470-476) T hree controlled clinical trials (the Lipid Research Clinics Coronary Primary Prevention Trial, the Helsinki Heart Study, and the Coronary Drug Project) have shown that the incidence rate of coronary heart disease can be reduced by drugs that lower total plasma cholesterol. [1][2][3] see p 694 Although reduction of total plasma cholesterol was a common feature of these trials, the drugs tested reduced cholesterol levels through different mechanisms and produced widely different patterns of lipoprotein transport. The mechanism(s) of benefit in these trials is believed due to a primary effect of lowering blood lipids or lipoproteins on coronary atherosclerosis at the level of the arterial wall.

Common carotid intima-media thickening can be reduced by colestipol-niacin treatment. Two-year image-processed carotid ultrasound trials can provide adequate power with 50 subjects per group to test for this treatment effect.

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