Overproduction of low density lipoproteins associated with coronary heart disease.

Abstract

The turnover rates of low density lipoprotein-apolipoprotein (apoLDL) were determined in eight men with coronary heart disease (CHD) and seven men matched for age, weight, and plasma lipid levels who were used for controls. The CHD patients were normocholesterolemic (plasma cholesterol = 204 ± 8 mg/dl SEM) as were the control subjects (227 ±15 mg/dl). The concentrations of plasma LDL cholesterol and apoLDL were similar for the two groups. In contrast, the synthetic rates of apoLDL were higher in the CHD patients (20.0 ± 1.8 mg/kg/day) than in the controls (12.9 ± 1.1 mg/kg/day) (p < 0.01). The ratios of protein-to-cholesterol in LDL averaged 19% higher in the CHD patients. These patients with CHD maintained normal LDL levels despite an over-production of apoLDL because of an increased capacity for LDL removal; their fractional catabolic rates of apoLDL averaged 43% higher than those of the controls. These findings indicate that some patients with CHD have abnormalities in the turnover of apoLDL, even with normal concentrations of LDL; these abnormalities may contribute to accelerated atherosclerosis. (Arteriosclerosis 3:40-46, January/February 1983) E levated levels of total plasma cholesterol and the major cholesterol-carrying lipoprotein, low density lipoprotein (LDL), are associated with increased risk for coronary heart disease (CHD).12 However, concentrations of plasma total and LDL cholesterol overlap considerably among people with and without premature CHD. Recently, high levels of LDL apolipoprotein B (apo B) have been reported to separate patients with CHD from unaffected people better than do total cholesterol, triglycerides (TG), or LDL cholesterol.3 In this same report, patients were described who had advanced atherosclerosis, elevated LDL apo B, but normal LDL cholesterol. Thus, abnormalities in metabolism of LDL apo B, which may not be reflected in LDL cholesterol concentrations, could contribute to atherosclerosis. To examine this possi- bility further, we undertook this study to determine the production and removal of LDL protein (apoLDL, which is over 90% apo B) in patients with CHD and in control patients matched for age, sex, and plasma lipid concentrations. Methods PatientsEight men with well-documented CHD and seven healthy men (controls) were studied (table 1). At the time of the study, the CHD patients were 60 ± 3 years old (SEM) (an age range of 49 to 71 years) and their ages at the clinical onset of CHD averaged 51 ± 3 years (from 43 to 66 years). Their mean body weight was 74 ± 2 kg (mean ideal weight = 108 ± 3%). In six patients, coronary artery bypass grafting was done an average of 6 years after the onset of CHD. The two patients without grafts had had previous myocardial infarctions proven by electrocardiograms and enzyme changes. Many patients had bruits over carotid and femoral arteries, but none had clinical heart failure. Also, none had xanthomata, xanthelasma, fasting or 2-hour postprandial hyperglycemia. Four patients (Nos. 1, 2, 3, and 4) were taking propranolol for hypertens...

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