Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.

Background-We examined the development of new diabetes mellitus in men aged 45 to 64 years during the West of Scotland Coronary Prevention Study. Methods and Results-Our definition of diabetes mellitus was based on the American Diabetic Association threshold of a blood glucose level of Ն7.0 mmol/L. Subjects who self-reported diabetes at baseline or had a baseline glucose level of Ն7.0 mmol/L were excluded from the analyses. A total of 5974 of the 6595 randomized subjects were included in the analysis, and 139 subjects became diabetic during the study. The baseline predictors of the transition from normal glucose control to diabetes were studied. In the univariate model, body mass index, log triglyceride, log white blood cell count, systolic blood pressure, total and HDL cholesterol, glucose, and randomized treatment assignment to pravastatin were significant predictors. In a multivariate model, body mass index, log triglyceride, glucose, and pravastatin therapy were retained as predictors of diabetes in this cohort. Conclusions-We concluded that the assignment to pravastatin therapy resulted in a 30% reduction (Pϭ0.042) in the hazard of becoming diabetic. By lowering plasma triglyceride levels, pravastatin therapy may favorably influence the development of diabetes, but other explanations, such as the anti-inflammatory properties of this drug in combination with its endothelial effects, cannot be excluded with these analyses.

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Summary and conclusions Blood viscosity (shear rate 100/s) and its major determinants (packed cell volume, plasma fibrinogen concentration, and plasma viscosity) were measured before coronary angiography in 50 men aged 30-55 and related to the extent of coronary artery disease. Twenty-six men had extensive disease (stenosis of two or three major coronary vessels), and 24 had either stenosis of one vessel or no stenosis. The 26 men with extensive disease had significantly higher mean blood viscosity than those with mild or no disease and 25 healthy controls (p <0 001). The increased viscosity was due partly to a higher packed cell volume and partly to a higher fibrinogen concentration; plasma viscosity was not significantly increased. These differences could not be explained by smoking history.These results suggest an association between increased blood viscosity and extensive coronary artery disease in men, which merits further investigation.

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Seven moderately hypercholesterolemic subjects were studied before and after 10 weeks of simvastatin therapy (20 mg/day). Therapy reduced low density lipoprotein (LDL) cholesterol by 39% (p<0.001), whereas high density lipoprotein and very low density lipoprotein (VLDL) cholesterol were unchanged. Apolipoprotein (apo) B-containing lipoproteins were divided into VLDL, (S, 60-400), VLDL 2 (S r 20-60), intermediate density lipoprotein , and LDL (S r 0-12), and metabolic changes were sought in dual-tracer VLDL] and VLDL 2 turnover studies. VLDL, apoB pool size was unaltered by therapy, as were its rates of synthesis, catabolism, and delipidation to VLDL 2 . Similarly, the VLDL 2 apoB pool size was unchanged, but its metabolic fate was altered. The IDL pool size fell significantly (27%, p< 0.01) due entirely to an increased fractional catabolism of the lipoprotein. In our subjects, the circulating mass of LDL apoB decreased (49%, p< 0.01) primarily due to a reduction in its synthesis. Before therapy, 30% of the apoB entering the delipidation cascade in these hyperlipidemic subjects was converted to LDL. On therapy the input remained the same, but direct catabolism from VLDL 2 and IDL was increased (p<0.05), and as a result only 16% eventually appeared in LDL. These kinetic changes were associated with a fall in particle cholesteryl ester content throughout the delipidation cascade. We also observed a link between LDL kinetics and its subfraction distribution. Simvastatin influences the metabolism of LDL, IDL, and VLDL 2 but not VLDL,. {Arteriosclerosis and Thrombosis 1993;13:170-189) KEY and more recently from the Helsinki Heart Study 3 has confirmed the importance of lipid lowering as a means of preventing coronary heart disease (CHD). Since the completion of these studies, more powerful lipid-regulating agents have become available; the most potent of these in terms of low density lipoprotein cholesterol (LDL-C) lowering are the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors or "statins." This is an important class of lipid-lowering drugs whose remarkable efficacy has been documented in studies of several different groups of patients. 4 " 10 The precise mechanism of action of these compounds, however, has not been fully elucidated. At first it was thought that they affected only LDL via activation of hepatic apolipoprotein (apo) B/E receptors. However, further experience has suggested that they have substantial effects on very low density In general, all statins have weak but significant plasma triglyceride-lowering properties; in type III hyperlipoproteinemic subjects it has been shown that statins can, uniquely among lipid-lowering drugs, correct the compositional abnormality seen in VLDL. 9 Investigations of the kinetic changes underlying the LDL reduction on statin therapy have revealed an unsuspected heterogeneity of response. Many subjects, particularly those with familial hypercholesterolemia (FH), exhibit an increase in apoLDL clearance while on the drug, 13 whereas in others decreas...

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