An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence.

Abstract

The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For every 1% reduction in cholesterol, an estimated 2.5% reduction in CHD incidence is indicated (95% CL: 1.1, 3.9). With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials. With regard to total mortality, this efficiency was higher in secondary than in primary preventive trials. The efficiency was also somewhat dependent on the baseline cholesterol level. This study shows that cholesterol reduction is effective in lowering CHD incidence, but cholesterol reduction must be at least 8-9% to be effective in lowering total mortality. (Circulation 1990;82:1916-1924 In the prevention of early occurrence of coronary heart disease (CHD), various strategies have been implemented based on the three most important coronary risk factors, that is, total cholesterol, blood pressure, and cigarette smoking. The evidence of cholesterol lowering as an efficient method of CHD risk reduction has been tested through a series of intervention trials. These include single and multifactor trials, and primary and secondary diet and drug trials. address the question of whether the effect of cholesterol lowering is dependent on design characteristics such as primary and secondary or diet and drug intervention.The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and CHD incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored.These questions are addressed through an overview analysis of all randomized controlled clinical trials involving designed cholesterol lowering. Total mortality and CHD incidence are the only end points under investigation. Trials with angiographic end points will not be discussed. MethodsThe criteria for inclusion of trials in this overview were 1) designed cholesterol lowering, 2) randomized design, and 3) total mortality or CHD incidence rep...

Role of the low density lipoprotein receptor in the flux of cholesterol through the plasma and across the tissues of the mouse.

“…Epidemiological data clearly support the view that the risk of developing atherosclerotic disease is determined, in a major way, by the steady-state concentration of cholesterol in the plasma carried in LDL (LDL-C) (29)(30)(31)(32). This steady-state LDL-C concentration is determined by four separate rate constants that include the LDL-C production rate (Jr), the maximal rate of LDL-C transport that can be achieved when all LDL receptors are occupied (Jm), the functional affinity of the LDL for its receptor (Kin), and the rate of LDL-C uptake by a process that apparently does not depend upon the LDLR (P) (33,34).…”

Cerivastatin (BAY w 6228): A Novel HMG‐CoA Reductase Inhibitor

“…Two in vivo experiments, the micronucleus assay in the mouse (350 m g k g single dose p.0.) and the dominant-lethal test in the mouse (25 …”

Cholesterol and triglyceride concentrations, birthweight and central obesity in pre-school children

“…1 This is partly due to the high mean cholesterol levels in this country, 2 as high cholesterol is related to a greater degree of atherosclerosis 3 and to increased coronary heart disease morbidity and mortality. 4 Strong relationships between blood lipid levels and anthropometry have been found in adults 5 ± 7 and school age children. 8 ± 11 Two particularly consistent relationships are the association of increased height with a more favourable blood lipid pro®le among children, and of obesity with a less favourable blood lipid pro®le among both adults and children.…”