A study of atherosclerosis regression in Macaca mulatta: II. Chemical changes in arteries from animals with atherosclerosis induced for 19 months then regressed for 24 months at plasma cholesterol concentrations of 300 or 200 mg/dl

Abstract

A clinically important question in people with existing atherosclerosis is whether a low concentration of plasma cholesterol attainable with diet or drug therapy influences preexisting atherosclerotic plaques and at what level of plasma cholesterol do these changes occur. Groups of young adult male rhesus monkeys were fed atherogenic diets for 19 months, then regression diets for 24 months. Regression diets contained sufficient cholesterol to maintain plasma cholesterol concentrations either at 302 ± 8 mg/dl, mean ± SEM (a concentration associated with a high risk for continued progression of atherosclerosis in man) or 194 ± 4 mg/dl (low risk for continued atherosclerosis development). A significantly greater amount of the accumulated arterial cholesterol, esterified cholesterol and phospholipid was removed in monkeys that underwent regression at 200 in comparison to 300 mg/dl. Decreases in arterial cholesterol in animals after 24 months at 200 mg/dl amounted to 100, 100, 93, and 96%, respectively, for carotid artery, thoracic aorta, abdominal aorta and iliaco-femoral artery in sharp contrast to decreases of only 80, 25, 56, and 72% in similar vessels of monkeys at the higher plasma cholesterol concentration. No major difference in arterial collagen or elastin was seen between the two regression groups. The frequency of mineralized plaques as assessed by aortic calcium accumulation was greater in the rhesus monkeys at the higher plasma cholesterol concentration during regression. Translated to human beings, these results suggest that for relatively uncomplicated fatty atherosclerotic lesions the plasma cholesterol concentration influences the degree of plaque regession and that significantly greater regression (as measured by a reduction in arterial lipid content) may be expected to occur at plasma cholesterol concentrations of 200 mg/dl as opposed to 300 mg/dl.