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Background-Ezetimibe has been shown to inhibit cholesterol absorption in animal models, but studies on cholesterol absorption in humans have not been performed thus far. Methods and Results-The effect of ezetimibe (10 mg/d) on cholesterol absorption and synthesis, sterol excretion, and plasma concentrations of cholesterol and noncholesterol sterols was investigated in a randomized, double-blind, placebo-controlled, crossover study in 18 patients with mild to moderate hypercholesterolemia. Treatment periods lasted 2 weeks with an intervening 2-week washout period. Fractional cholesterol absorption rates averaged 49.8Ϯ13.8% on placebo and 22.7Ϯ25.8% on ezetimibe, indicating a reduction of 54% (geometric mean ratio; PϽ0.001). Cholesterol synthesis increased by 89% from 931Ϯ1027 mg/d on placebo to 1763Ϯ1098 mg/d on ezetimibe (PϽ0.001), while the ratio of lathosterol-to-cholesterol, an indirect marker of cholesterol synthesis, was increased by 72% (PϽ0.001). Bile acid synthesis was insignificantly increased (placebo: 264Ϯ209 mg/d, ezetimibe: 308Ϯ184 mg/d; Pϭ0.068). Mean percent changes from baseline for LDL and total cholesterol after ezetimibe treatment were Ϫ20.4% and Ϫ15.1%, respectively (PϽ0.001 for both), whereas campesterol and sitosterol were decreased by Ϫ48% and Ϫ41%, respectively. Conclusion-In humans, ezetimibe inhibits cholesterol absorption and promotes a compensatory increase of cholesterol synthesis, followed by clinically relevant reductions in LDL and total cholesterol concentrations. Ezetimibe also reduces plasma concentrations of the noncholesterol sterols sitosterol and campesterol, suggesting an effect on the absorption of these compounds as well.

T his document presents guidelines for reducing the risk of cardiovascular disease by dietary and other lifestyle practices. Since the previous publication of these guidelines by the American Heart Association, 1 the overall approach has been modified to emphasize their relation to specific goals that the AHA considers of greatest importance for lowering the risk of heart disease and stroke. The revised guidelines place increased emphasis on foods and an overall eating pattern and the need for all Americans to achieve and maintain a healthy body weight (Table).The major guidelines are designed for the general population and collectively replace the "Step 1" designation used for earlier AHA population-wide dietary recommendations. More individualized approaches involving medical nutrition therapy for specific subgroups (for example, those with lipid disorders, diabetes, and preexisting cardiovascular disease) replace the previous "Step 2" diet for higher-risk individuals.The major emphasis for weight management should be on avoidance of excess total energy intake and a regular pattern of physical activity. Fat intake of Յ30% of total energy is recommended to assist in limiting consumption of total energy as well as saturated fat. The guidelines continue to advocate a population-wide limitation of dietary saturated fat to Ͻ10% of energy and cholesterol to Ͻ300 mg/d. Specific intakes for individuals should be based on cholesterol and lipoprotein levels and the presence of existing heart disease, diabetes, and other risk factors. Because of increased evidence for the cardiovascular benefits of fish (particularly fatty fish), consumption of at least 2 fish servings per week is now recommended. Finally, recent studies support a major benefit on blood pressure of consuming vegetables, fruits, and low-fat dairy products, as well as limiting salt intake (Ͻ6 grams per day) and alcohol (no more than 2 drinks per day for men and 1 for women) and maintaining a healthy body weight. Overview and SummaryThe AHA has a long-standing commitment to the promotion of lifestyle practices aimed at preventing the development or recurrence of heart and blood vessel diseases and promoting overall well-being. An important component of this mission has been the provision of dietary guidelines for the American population that are based on the best available scientific evidence. The present statement formulates the core elements of population-wide recommendations for cardiovascular disease prevention and treatment that are supported by decades of research. This revised statement also provides a summary of a number of important ancillary issues, including those for which the scientific evidence is deemed insufficient to make specific recommendations.Three principles underlie the current guidelines:• There are dietary and other lifestyle practices that all individuals can safely follow throughout the life span as a foundation for achieving and maintaining cardiovascular and overall health.• Healthy dietary practices are based on one's overall p...

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