Intermediate-density lipoproteins and progression of coronary artery disease in hypercholesterolaemic men.

Lipoprotein mass concentrations were measured by analytical ultracentrifugation in a subset of 57 hypercholesterolaemic male participants in the National Heart, Lung, and Blood Institute Type II Coronary Intervention Study. 2-year changes in levels of intermediate-density lipoproteins (IDL) of flotation rate 12-20 were strongly predictive of progression of coronary artery disease at 5 years. Changes in serum mass concentrations of low-density lipoproteins (LDL; flotation rate 0-12), very-low-density lipoproteins (VLDL; flotation rate 20-400), high-density lipoproteins (HDL), and the HDL2 and HDL3 subfractions did not differ significantly between men with and without definite progression of coronary artery disease. The relation of IDL mass to disease progression remained significant (p less than 0.05) after adjustment for group assignment to cholestyramine treatment or placebo and was only slightly reduced (p less than or equal to 0.06) by adjustment for changes in LDL mass concentrations. Changes in IDL mass and ratios of HDL-cholesterol to total-cholesterol or LDL-cholesterol were inversely correlated and had a similar ability to predict progression. The findings are consistent with earlier evidence that IDL are directly involved in the development of coronary artery disease and suggest that ratios of HDL-cholesterol to total-cholesterol or LDL-cholesterol may be indicators of coronary disease risk partly owing to relations with IDL metabolism.

Secondary prevention and lipid lowering: results and implications.

In a secondary prevention trial conducted by the National Heart, Lung, and Blood Institute, the effect of lipid lowering by drug intervention on the progression of existing coronary artery disease (CAD) was evaluated in type II hyperlipidemic patients. This first randomized, secondary prevention trial compared the effect of cholestyramine and diet with that of placebo and diet in 143 patients over a 5-year period. End points evaluated were progression or regression of CAD, as demonstrated by angiographic changes compared with baseline angiograms. The cholestyramine-treated group demonstrated a significant reduction in total cholesterol and in low-density lipoprotein cholesterol (LDL) levels as compared with placebo, and an 8% increase in high-density lipoprotein cholesterol (HDL). A statistically significant result supporting the use of cholestyramine treatment was found in one category of CAD progression.

Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study.

In the National Heart, Lung and Blood Institute Type II Coronary Intervention Study, patients with Type II hyperlipoproteinemia and coronary artery disease (CAD) were placed on a low-fat, low-cholesterol diet and then were randomly allocated to receive either 6 g cholestyramine four times daily or placebo. This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography. Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group. Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant. However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05). Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant. Thus, although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.

The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of NHLBI Type II Coronary Intervention Study.

The National Heart, Lung and Blood Institute Type II Coronary Intervention Study, a double-blind, placebo-controlled trial, evaluated the efficacy of reduction in cholesterol levels induced by cholestyramine on progression of coronary artery disease (CAD). The rate of CAD progression in patients treated with cholestyramine plus diet was compared with that of patients treated with placebo plus diet. CAD progression was defined angiographically. Significant decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDLc) and increases in high-density lipoprotein cholesterol (HDLc), as well as in HDLc/TC and HDLc/LDLc ratios, were observed with cholestyramine. HDLc change was due to increase in HDL2A and HDL2B. When the relationship between CAD progression and lipid changes was examined independent of specific treatment group, a significant inverse relationship was found between progression at 5 years and the combination of an increase in HDLc and a decrease in LDLc; changes in HDLc/TC and HDLc/LDLc were the best predictors of CAD change. While the testing of these relationships independent of treatment group was not part of the initial study design, the trends were observed in both the placebo-treated and cholestyramine-treated groups. Moreover, with multivariate analysis, the effect of cholestyramine treatment on CAD progression was eliminated by adding changes in HDLc/TC to the regression model. These findings support the hypothesis that increases in HDLc and decreases in TC (or LDLc) can prevent or delay CAD progression.

Reliability of assessing change with sequential coronary angiography.

Data are presented from a study evaluating the reliability of sequential angiography in estimating changes in coronary lesions. Three panels of three expert angiographers each read on two separate, independent occasions 18 sets of paired angiograms taken 24 months apart. All readers were blinded to the temporal sequence of the films, clinical data, and ventriculography information. The need for simultaneous viewing and reading of the two films, for training sessions, and for allowance to be made for apparent differences arising from boundary definitions prior to final analysis was demonstrated. Under stringent conditions (determination of change based on agreement of at least two out of three panels of physicians) it was possible to ascertain change in coronary atherosclerosis from sequential sets of coronary angiograms with good reliability. However, single-panel readings yielded an unacceptable overestimate of the number of patients with lesion changes.

National Heart, Lung, and Blood Institute type II Coronary Intervention Study: design, methods, and baseline characteristics.

The Type II Coronary Intervention Study (Type II Study) is a double-blind, randomized, placebo-controlled clinical trial conducted by the Division of Intramural Research of the National Heart, Lung, and Blood Institute of Bethesda, Maryland. The study was designed to evaluate the 5-year treatment effect of cholestyramine on low density lipoprotein (LDL) cholesterol and on lesions in the coronary arteries. One hundred forty-three patients with Type II hyperlipoproteinemia (elevated LDL cholesterol) and coronary artery disease (CAD) were entered into the study between 1972 and 1976. Patients were stratified by sex and extent of coronary disease as defined angiographically and were randomly allocated to a daily dosage of 24 g cholestyramine and diet (treatment group) or placebo and diet (control group). Changes in the coronary arteries were evaluated by sequential coronary angiography carried out before and after five years of treatment. This report describes the trial design and baseline characteristics of the study patients.

Limitations of the electrocardiographic response to exercise in predicting coronary-artery disease.

The electrocardiographic response to exercise was compared with the results of coronary angiography in 89 patients with Type II hyperlipoproteinemia who had previous myocardial infarction or typical angina or both (43 patients)(Group A), "atypical angina" (16 patients)(Group B)or positive electrocardiographic response to exercise without other evidence of cardiac disease (30 patients)(Group C). Thirty-nine of 43 in Group A had greater than or equal to 50 per cent stenosis, and 26 (67%) of these 39 had negative exercise tests. In Group B, five of the 16 had greater than or equal to 50% stenosis, and three had positive exercise tests (one patient had a false-positive test). In Group C, eleven of 30(37%) had greater than or equal to 50% stenosis; however, nine (30%) had minor stenosis (less than or equal to 50%), and 10(33%) normal coronary arteries. The diagnostic usefulness of exercise electrocardiography is limited. False-negative responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic patients.