Chapter 31

Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-induced conditions, such as coronary heart disease (CHD), ischemic cerebrovascular disease, and peripheral vascular disease. Although the incidence of these atherosclerosis-related cardiovascular disease (CVD) events has declined in the U.S., these conditions cause morbidity or mortality in a majority of middle-aged or older adults and account for about one-third of all deaths of persons in this age range. The incidence and absolute number of annual events will likely increase over the next decade because of the epidemic of obesity and the aging of the U.S. population. Dyslipidemias, including hyperlipidemia (hypercholesterolemia) and low levels of high-density-lipoprotein cholesterol (HDL-C), are major causes of increased atherogenic risk; both genetic disorders and lifestyle (sedentary behavior and diets high in calories, saturated fat, and cholesterol) contribute to the dyslipidemias seen in countries around the world. For many individuals, alterations in lifestyle have a far greater potential for reducing vascular disease risk and at a lower cost than drug therapy. When pharmacotherpy is indicated, providers can choose from multiple agents with proven efficacy.

Recognition that dyslipidemia is a risk factor has led to the development of drugs that modify cholesterol levels. This chapter focuses on the following classes of drugs:

• 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors—the statins
• Bile acid–binding resins
• Nicotinic acid (niacin)
• Fibric acid derivatives
• The cholesterol absorption inhibitor ezetimibe

These drugs provide benefit in patients across the entire spectrum of cholesterol levels, primarily by reducing levels of low-density-lipoprotein cholesterol (LDL-C).

In early well-controlled clinical trials employing drug regimens that reduce LDL-C levels moderately (30-40%), fatal and nonfatal CHD events and strokes were reduced by as much as 30-40% (Grundy et al., 2004b). Clinical trial data support extending lipid-modifying therapy to high-risk patients whose major lipid risk factor is a reduced plasma level of HDL-C, even if their LDL-C level does not meet the existing threshold values for initiating hypolipidemic drug therapy (Grundy et al., 2004b). In patients with low HDL-C and average LDL-C levels, appropriate drug therapy reduced CHD endpoint events by 20-35% (Heart Protection Study Collaborative Group, 2002). Because two-thirds of patients with CHD in the U.S. have low HDL-C levels (<40 mg/dL in men, <50 mg/dL in women), it is important to include low-HDL-C patients in management guidelines for dyslipidemia, even if their LDL-C levels are in the normal range (Bersot et al., 2003).

Severe hypertriglyceridemia (i.e., triglyceride levels of >1000 mg/dL) requires therapy to prevent pancreatitis. It is unclear whether hypertriglyceridemia is an independent risk factor for developing atherothrombotic CVD (Sarwar et al., 2007). Moderately elevated triglyceride levels (150-400 mg/dL) are of concern because they often occur as part of the metabolic syndrome, which includes insulin resistance, obesity, hypertension, low HDL-C levels, a procoagulant state, and substantially increased risk of CVD. The atherogenic dyslipidemia in patients with the metabolic syndrome also is characterized by lipid-depleted LDL (sometimes referred to as "small, dense LDL") (Grundy et al., 2004a). The metabolic syndrome affects ∼25% of adults and is common in CVD patients; hence, identification ...

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