Drug Topics - November 5, 2007 - (Page 30)

30 DRUG TOPICS NOVEMBER 5, 2007 www.drugtopics.com CONTINUING EDUCATION GOAL To enhance pharmacists’ understanding of the increasing importance of appropriately controlled high-density lipoprotein cholesterol (HDL-C) in preventing cardiovascular events ATP III guidelines provide a classification system for HDLC levels. Those measurements falling below 40 mg/dl are classified as “low” and those over 60 mg/dl are classified as “high.” In addition, HDL-C is one of five criteria assessed in the determination of the LDL goal. HDL goals above 60 mg/dl are considered “negative” risk factors and allow for the subtraction of one risk factor from the total count. HDL-C is also a component of the Framingham calculation, a value that estimates a patient’s 10-year risk for heart disease. Additionally, the metabolic syndrome is a constellation of risk factors for heart disease, one of which includes the presence of low HDL-C levels. CREDIT This lesson provides two hours of CE credit and requires a passing grade of 70%.* OBJECTIVES Upon completion of the article, pharmacists and technicians should be able to: Describe the epidemiology and pathophysiology of low HDL-C levels Review the current nonpharmacologic strategies that can modify HDL-C Explain the current pharmacologic therapies used to modify HDL-C Recommend appropriate nonpharmacologic and pharmacologic strategies and monitoring for a given patient with a low HDL-C level Identify and describe emerging therapies targeting HDL-C, including recent data Discuss the role of the pharmacist in the management of patients with low HDL-C levels *To receive credit you must score 70% or higher on the quiz and complete the evaluation. Upon successful completion, the University of Florida College of Pharmacy will mail Statements of Credit for written quizzes within 10 working days. Participants completing the program on-line may print a Statement of Credit after successfully completing the program. Background and epidemiology Cardiovascular disease is currently the No. 1 cause of mortality in the United States. Many factors have been linked to the increasing risk for heart disease, one of which is dyslipidemia. Currently, in the Third Edition of the Adult Treatment Panel (ATP III) from the National Cholesterol Education Program, the commonly accepted guidelines for the management of dyslipidemia, LDLC is cited as the primary target of therapy in most cases, owing to its strong link to cardiovascular disease. However, data from the Framingham Heart Study suggests that low HDL-C levels are also implicated as an important, independent risk factor for the development of cardiovascular disease. In fact, an estimated 3% to 6% of women and 16% to 18% of men have HDL-C levels <35 mg/dl, which is considered a low value. In addition, there is an eightfold risk for the development of cardiovascular disease in patients with an HDL-C level 65 mg/dl. It is estimated that each 1 mg/dl reduction in HDL-C levels is associated with a 2% to 3% increase in the risk for heart disease, while each 1 mg/dl increase in HDL-C levels is linked to a 6% reduction in risk. Pathophysiology The cardioprotective effects of HDL-C are still being elucidated. One proposed mechanism is via reverse cholesterol transport. HDL-C is responsible for taking excess cholesterol from foam cells (i.e., cells involved in the development of the fibrous cap of the atherosclerotic lesion) in the peripheral tissue to the liver for breakdown or excretion into bile. As a result, there is a reduction in cholesterol buildup along the arteries. HDL-C is also involved in the cholesteryl ester transfer protein (CETP)mediated exchange of very low density lipoprotein (VLDL)-rich triglycerides for cholesteryl esters. The now TG-rich HDL-C particles are targets for plasma lipases that reduce the size of the particles and are rapidly cleared from the plasma. This process is enhanced in the presence of elevated TG. Antioxidant, anti-inflammatory, and vasoprotective effects are also believed to play a major role in the antiatherogenic effects of HDL-C. HDL-C particles are composed of apolipoproteins. These are proteins that assist in the process of transporting lipids, and they have different functions. The primary apolipoprotein that has been implicated in the protective effects of HDL-C is apoA-I. It is involved as a structural component of the HDL-C particle and is an activator of lecithin-cholesterol acyltransferase (LCAT), an enzyme responsible for stimulating the transfer and esterification of excess cholesterol from the foam cells to the liver. On the other hand, apoA-II is a structural component of HDL-C that is believed to exert proatherogenic effects through its activation of hepatic lipases, the enzymes responsible for the reduction in HDL-C particle size. Nonpharmacologic interventions to raise HDL-C levels Aerobic exercise has been shown to improve HDL-C levels by 5% to 10%. In a meta-analysis, exercise was associated with a statistically significant 2.53 mg/dl (95% CI [confidence interval] 1.36–3.70) increase in HDL-C levels. For improvements in lipid parameters, a patient should ideally perform an aerobic exercise activity for at least 120 minutes each week divided into four 30-minute sessions. Routine alcohol intake of 10 to 20 gm a day (approximately one to two drinks per day) has been shown to increase the HDL-C level by about 12% after four to five weeks of consumption. However, excessive alcohol intake is linked to elevated TG, thus increasing the risk for heart disease. The beneficial effects of alcohol are mediated through an increase in the transport of apoA-I. In the Copenhagen City Heart Study, patients drinking wine appeared to have a reduced risk for heart disease. However, this was not noted in patients consuming spirits or beer. Additionally, consuming two drinks per day was associat- http://www.drugtopics.com

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Drug Topics - November 5, 2007 Contents Latebreakers Latebreakers in Depth Letters Rx Care Community Practice 150 Years of American Pharmacy Hospital Practice Pharmacists at Risk Government and Law High-Density Lipoprotein New Products Advertisers Index Classified Viewpoint

Drug Topics - November 5, 2007

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