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Biomedical subjects

R I Levy

Publications and source records attributed to R I Levy.

At least 37 records · Page 2Linked to original sources
PubMed1985

Primary prevention of coronary heart disease by lowering lipids: results and implications.

Evidence to support the hypothesis that lowering total and low-density lipoprotein (LDL) cholesterol may reduce heart attacks and heart deaths has, until recently, not been available. Early primary prevention trials lacked definitive data on these "hard" end points. Since 1980, five primary prevention trials have attempted to demonstrate the benefit of lowering cholesterol. Three of these involved diet: the Oslo Heart Trial and both the European and American Multiple Risk Factor Intervention Trials (MRFITs). Two involved lipid-lowering drugs: the European Clofibrate Primary Prevention Trial and the National Heart, Lung, and Blood Institute's recently concluded Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). The Olso Heart Trial suggested a benefit from the dietary reduction of cholesterol; results of the other studies of diet were equivocal. Although clofibrate did demonstrate a reduced incidence of heart attacks in the treated group, the cardiac mortality rate was not altered in this group. A significant increase in the all-cause mortality rate (other than ischemic heart disease) observed in this trial in treated subjects makes clofibrate difficult to recommend. The LRC-CPPT study, involving cholestyramine, has provided conclusive evidence concerning the benefits of lowering cholesterol: significant reductions were observed in all cardiovascular end points measured, including the development of angina and positive exercise stress tests, referral for bypass surgery, and the hard primary study end point heart attack and heart attack death.

Cholesterol, LDL↗
PubMed1985

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.

Angiocardiography↗
PubMed1984

Causes of the decrease in cardiovascular mortality.

In the last 15 years there has been a dramatic, unprecedented decrease in the mortality rate from cardiovascular disease in the United States, especially from coronary heart disease and stroke. Possible causes of the decline in the coronary heart disease mortality rate include the development of the concept of acute coronary care, new drugs, sophisticated surgical techniques such as coronary artery bypass, noninvasive diagnostic methods for earlier disease detection, and the identification of specific cardiovascular risk factors. The decrease has been temporarily related to increased risk factor awareness and modification (cigarette smoking cessation, hypertension control, diet change and reduction in cholesterol). Thus, both primary prevention through lifestyle changes and improved treatment regimens have played a role in the decline. Recent studies showing the benefit of cholesterol reduction emphasize the potential for even greater decreases.

Adult↗
PubMed1984

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.

Adult↗
PubMed1984

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.

Adult↗
PubMed1983

Current status of the cholesterol controversy.

It has been established that elevated levels of serum cholesterol, particularly of the low-density lipoprotein fraction, are associated with increased risk of myocardial infarction. There is no doubt that both low-density lipoprotein cholesterol levels and total plasma cholesterol levels can be lowered by diet and/or by drug therapy in almost all patients. The true controversy lies in whether intervention is associated with an actual reduction in the incidence of myocardial infarction. A great deal of circumstantial evidence suggests a positive correlation, but to date this can not yet be supported by direct data from clinical trials performed in man. It is, therefore, not certain whether a lowering of the serum cholesterol level results in a simultaneous reduction of risk.

Animals↗
PubMed1983

The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females.

The effects of estrogen administration (ethinyl estradiol; 0.1 mg, orally, daily) on plasma lipoprotein metabolism were investigated in five normolipidemic premenopausal females. Estrogen administration resulted in significant (P less than 0.05) mean increases in plasma cholesterol, triglyceride, very low density lipoprotein (VLDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol of 18.8%, 87.0%, 123.1%, and 38.3%, respectively. Analytical ultracentrifugation demonstrated that HDL increases occurred mainly in the HDL2b subfraction (150.0% increase). Lipoprotein compositional analysis showed that estrogen administration caused significant increases in all VLDL and HDL constituents (protein, cholesterol, phospholipid, and triglyceride) as well as VLDL apolipoprotein (apo) B (118.9% increase) and HDL apoA-I (27.4% increase). No significant changes in LDL constituents were noted. Measurement of lipoprotein lipase and hepatic lipase enzymic activity in post-heparin plasma revealed no major change in lipoprotein lipase activity, but showed a significant decrease (43.8%) in hepatic lipase activity during estrogen administration. Radioiodinated VLDL and HDL kinetic data indicated increased VLDL apoB (86.1% rise) and HDL apoA-I (24.9% rise) synthesis during estrogen administration. These data are consistent with the concept that estrogen administration at the dose level studied in premenopausal females causes significant elevations in VLDL and HDL constituents, associated with enhanced production of VLDL apoB and HDL apoA-I.

Adult↗
PubMed1982

Cardiovascular research: decades of progress, a decade of promise.

Mortality due to cardiovascular diseases has decreased more than 30 percent in the last 30 years, and this decline has accelerated so much that over 60 percent of it has occurred between 1970 and 1980. The past and present contributions of advances in cardiovascular research to this decline are reviewed. Although three have been significant research accomplishments, too many people still die of heart and blood vessel diseases. Continued emphasis must be placed on research in the areas of etiology and pathogenesis, on validating potentially beneficial research hypotheses, and on the translation and dissemination of research results to the health care practitioner and the public. Only then can our long-term goal, the prevention of cardiovascular disease, be fully realized.

Arrhythmias, Cardiac↗
PubMed1982

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.

Coronary Angiography↗
PubMed1982

Initiating large-scale clinical trials.

Large-scale clinical trials and their great potential impact on medical practice and on future research require extensive resources. Therefore, decisions to undertake such clinical trials must be made analytically and deliberately. This paper focuses on the decision and management processes used to initiate clinical trials in the National Heart, Lung, and Blood Institute, emphasizing the basis or rationale for the Institute to undertake a trial. The paper discusses two recent examples of the application of the process--a trial on drug treatment for mild hypertension that was considered and rejected by the Institute, and a trial on the effect of beta-blocker drugs to reduce post-myocardial infarction mortality, a trial that is now underway.

Adrenergic beta-Antagonists↗
PubMed1982

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.

Adult↗