Lipid-Lowering Trial Research Articles

Heterogeneity of plasma low-density lipoproteins and atherosclerosis risk.

Increased levels of IDL and small, dense LDL are associated with the risk of coronary artery disease. Possible mechanisms include increased susceptibility of small, dense LDL to oxidation, and to other pathologic effects, such as increased retention in the arterial wall. Beneficial effects of a low-fat diet and certain lipid-lowering therapies on the levels and properties of small, dense LDL or their precursors may contribute substantially to the reductions in coronary atherosclerosis observed in several lipid-lowering trials.

Dietary intervention to lower serum LDL-cholesterol and meet NCEP-ATP guidelines in a drug lipid lowering trial

Dietary intervention to lower serum LDL-cholesterol and meet NCEP-ATP guidelines in a drug lipid lowering trial

Willingness to pay for lipid lowering: a health production function approach

This Paper reports the results of an experiment of measuring willingness to pay (WTP) for lipid lowering. WTP is derived from a theoretical model of health risk reductions, using a health production function approach. A survey of about 700 persons randomized into a lipid lowering trial in Sweden is used to estimate WTP. The willingness to give up time (WTGT) to take part in a lipid lowering programme is also measured in the survey, to assess its relationship to WTP. The response rates on the WTP and WTGT qusetions are 94% and 96%, respectively, and the patients are on average perpared to pay about Skr 350 per month or devote about 5 h of leisure time per week to get normal lipid levels. The Correlation of WTP and WTGT is 0.45 and highly significant. The results of regression of WTP and WTGT are in accordance with the theoretical predictions with a higher valuation for a greater perceived difference in health status with and without treatment. The income elasticity is also positive as expected.

Dyslipidemia in type II Diabetes: Implications for Therapeutic Intervention

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.

Program on the surgical control of the hyperlipidemias (POSCH): Patient entry characteristics

The entry characteristics of patients in the Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized, controlled, clinical trial, are described in this article. The primary objective addressed by POSCH was whether lowering total plasma cholesterol by partial ileal bypass surgery results in a reduction in mortality and morbidity in post-myocardial infarction patients. Between 1975 and 1983, 838 patients between the ages of 30 and 64 years were randomized into POSCH. The mean age at entry was 51 years, and 91% of the patients were men. The mean time between myocardial infarction and entry was 2.2 years. The mean baseline total plasma cholesterol was 251 mg/dl, with a mean LDL-cholesterol of 179 mg/dl and a mean HDL-cholesterol of 40 mg/dl. Significant disease (⩾50% occlusion) of one or more major coronary arteries was found in 91% of the patients. In addition to a description of the POSCH patient population at entry, comparisons of the POSCH patient population to populations of participants in other lipid-lowering trials are presented to provide a perspective on how POSCH relates to these trials.

The Influence of Diet on the Appearance of New Lesions in Human Coronary Arteries

The Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of blood lipid lowering, demonstrated significant benefit in 2-year coronary angiograms. Using angiograms of subjects in the Cholesterol Lowering Atherosclerosis Study who received a placebo and 24-hour dietary recall data, we performed an epidemiologic study of risk factors for formation of new atherosclerotic lesions. Age and baseline plus on-trial lipid levels, blood pressure levels, and diet variables were included. Significant dietary energy sources were protein, carbohydrate, alcohol, total fat, and polyunsaturated fat. Each quartile of increased consumption of total fat and polyunsaturated fat was associated with a significant increase in risk of new lesions. Increased intake of lauric, oleic, and linoleic acids significantly increased risk. Subjects in the Cholesterol Lowering Atherosclerosis Study in whom new lesions did not develop increased dietary protein to compensate for reduced intake of fat by substituting low-fat meats and dairy products for high-fat meats and dairy products. These results indicate that when total and saturated fat intakes are reduced to levels recommended by the National Cholesterol Education Program, protein and carbohydrate are preferred substitutes for fat calories, rather than monounsaturated or polyunsaturated fat.

Glycol methacrylate embedding for light microscopy. I. enzyme histochemistry on semithin sections of undecalcified marrow cores.

A simple, routine procedure for water miscible glycol methacrylate (GMA) embedding of undecalcified bone marrow cores, which preserves the activity of enzymes useful in diagnosing various haematopoietic disorders, is described. The GMA used in this study has a low acid content that eliminates background staining, and the modified May-Grünwald-Giemsa stain provides good definition and excellent colour differentiation of various haematopoietic cells in the bone marrow, thereby providing optimal conditions for the study of the morphology and enzyme activity of bone marrow cells in the same preparation. The method is simple, reproducible, requires no expensive equipment, and is suitable for routine processing of small bone marrow cores in any histopathology or haematology laboratory.

Maximum lipid reduction by partial ileal bypass: a test of the lipid-atherosclerosis hypothesis.

Atherosclerosis is the process responsible for our national epidemic of coronary heart disease. A primary and proven atherosclerotic risk factor is the plasma cholesterol concentration. Yet, proof that a reduction in plasma cholesterol level results in a reduction in the incidence or severity of atherosclerosis and atherosclerotic cardiovascular disease still requires conclusive documentation. The controversial methods of operation and inconclusive results of concluded first and second generation trials are reviewed. These data clearly demonstrate that a definitive test of the lipid hypothesis has not been reported. Evidence is presented to show that the partial ileal bypass operation most nearly fulfills the six features of an "ideal" lipid lowering trial modality: maximum effectiveness (50% cholesterol reduction); known mechanism of action; no response "escape" or "rebound"; obligatory effect without patient cooperation; minimal side effects; and relative safety. The basic design and protocol of the National Heart and Lung Institute Program on Surgical Control of the Hyperlipidemias, a secondary intervention trial using a combination of diet therapy and partial ileal bypass surgery, are outlined.