This research will study patients who have combined hyperlipidemia (increased blood levels of cholesterol and triglycerides). The study aims to look at the effects of simvastatin (Zocor) an approved drug for the treatment of hypercholesterolemia in patients who have elevated levels of blood cholesterol and concurrently moderately increased levels of blood triglycerides. Ten to twelve patients will be enrolled in the study at OHSU and it is planned to study a total of 50-60 patients at other participating centers in the United States. The purpose of this study is to assess how the body uses fats that may be eaten during the day and how the cholesterol-lowering drug simvastatin (Zocor) may reduce these fats in the blood after a fat-rich meal similar to a large milk-shake. We are also interested in assessing the effects of simvastatin on the body's production of cholesterol which will be measured by determination of the concentrations of a precursor of cholesterol which is excreted in the urine and how treatment with simvastatin affects the ability of white blood cells to take up cholesterol from the blood. We are also interested in measuring two enzymes known as lipoprotein lipase and hepatic lipase, which are responsible for the removal of the particles in the blood stream that contain cholesterol and other fats including new fat that enters the body after people have eaten a meal. We are trying to find out if treatment with simvastatin in addition to reducing concentrations of LDL cholesterol and triglyceride-rich lipoproteins can enhance clearance of fatty particles from the blood stream after ingestion of a fatty meal. These cholesterol-rich lipoproteins may increase the risk of developing atherosclerosis (the most common form of heart disease) and if simvastatin is shown to enhance their clearance this would be potentially of therapeutic benefit in reducing the risk of heart disease in patients with high blood levels of cholesterol and triglycerides. Until recently the maximal recommended dose of simvastatin for use in the treatment of hypercholesterolemia was 40 mg per day but a higher dose (80 mg per day) was approved in July 1998 by the FDA for the treatment of hypercholesterolemia and has been given to about 1,500 patients for a period of up to one year with a good safety profile. Participants in this study will receive three treatment periods, one of which will be a placebo, one will be simvastatin 20 mg per day and the third will be simvastatin 80 mg per day. Neither the participant nor the investigators will know which treatment is received although this information can be available if medically necessary. Participants will be asked to take two tablets of medications (a combination of simvastatin and placebo) once daily in the evening for a total period of 24 weeks.
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