The term dyslipidemia describes many acquired and genetic lipoprotein disorders causing abnormal levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (Tables 1 and 21,2). Combined with high-fat diets, obesity, and physical inactivity, dyslipidemia has created epidemic atherosclerotic disease?the most common cause of death among Americans.3
Dyslipidemia also contributes to atherogenesis, pancreatitis, and fatty liver disease. Elevated plasma LDL levels and reduced HDL levels clearly increase coronary artery disease (CAD) risk and early mortality. The association of untreated hypertriglyceridemia with CAD is unclear, but elevated triglyceride levels increase pancreatitis risk.
Primary dyslipidemia results from a confluence of factors affecting lipoprotein metabolism. Secondary dyslipidemia stems from various pathologies, such as endocrine disorders, untreated hyperglycemia, hypothyroidism, nephrotic syndrome, chronic renal failure, or gastrointestinal disorders. Additionally, drugs (eg, antiviral HIV agents) may induce dyslipidemia.
Manifestations of dyslipidemia may include concurrent elevated cholesterol and triglyceride levels or only elevated triglyceride levels or low HDL levels. Metabolic syndrome is one of the most frequently encountered dyslipidemic conditions.4 It is closely allied with type 2 diabetes. Visceral obesity and insulin resistance are common in patients with this syndrome.
Prevention and Outcomes
Research confirms that lipid-lowering strategies, including pharmacotherapy, reduce total coronary events, procedures (eg, bypass surgery, angioplasty), cardiovascular hospitalizations, and stroke.5-7 Primary intervention with drug therapy in persons with low-to-moderate atherosclerotic risk, however, is controversial.8 Secondary prevention?lipid-lowering therapy in patients with confirmed coronary disease and/or with abnormal lipids?reduces mortality and further decreases coronary events, surgeries, and stroke. Patients who present with the highest risk accrue the greatest gains.9-11
Lowering cholesterol levels, especially LDL levels, can arrest or reverse atherosclerosis. Each 10% cholesterol-level reduction is associated with an ~20% to 30% reduction in heart disease incidence.12 Experts recommend first increasing physical activity, reducing dietary cholesterol and saturated fat, and trying weight loss.
Drug therapy is only rational if the type of hyperlipoproteinemia is defined and baseline serum cholesterol and triglyceride levels documented. Several classes of drugs (Table 3) reduce LDL cholesterol.3,12 Should cholesterol and triglyceride levels fail to decrease or triglyceride levels rise significantly, medication should be discontinued.
Until the mid 1980s, the intestinally active bile-acid sequestrants and niacin were the only proven pharmacologic interventions available to reduce LDL levels and decrease coronary risk. Adherence, however, was a concern, partly due to their poor tolerability and their tendency to increase triglyceride levels in patients with high baseline plasma triglycerides.
The discovery of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) changed clinical practice due to their robust effects on LDL cholesterol and their improved tolerability and safety profile. To date, clinical trials have proven the value of statins in reducing morbidity and mortality, including stroke. Some benefits have been attributed to their pleiotropic (multisystemic) effects, but their propensity to reduce LDL cholesterol levels appears to be the major cause of risk reduction.3
Recently, the introduction of the intestinally active agent ezetimibe created new monotherapy and combination approaches. Unlike bile-acid sequestrants, ezetimibe directly inhibits cholesterol absorption. Ezetimibe may reduce LDL cholesterol by ~20% as monotherapy or in combination with other lipid-lowering agents.13 Unlike the bile-acid sequestrants, ezetimibe does not increase plasma triglyceride levels. Clinical trials with cardiovascular end points are ongoing.3
The fibrates and niacin are preferred drugs for hypertriglyceridemia, with niacin best for raising HDL cholesterol levels. In patients with type 2 diabetes mellitus, niacin may aggravate insulin sensitivity. Fibrates are preferred for patients with marked hypertriglyceridemia for essential pancreatitis prevention. They also modestly improve HDL cholesterol levels. Omega-3 fatty acids (eg, those found in marine oils) also have been used for hypertriglyceridemia, especially when other therapies fail.
When both LDL cholesterol and triglyceride levels are elevated or when monotherapy fails, a combination of 2 drugs from different classes or, sometimes, triple therapy (eg, statins, niacin, and an intestinally active agent) is required.
Statin therapy is effective in the elderly and is probably indicated for high-risk individuals who have preexisting atherosclerosis after a thorough risk-benefit analysis is done.8,14,15 In women, dyslipidemia increases after menopause.16 Estrogen replacement therapy may lower cholesterol levels, but combined oral estrogen and progesterone does not protect women from CAD and may have adverse effects.17 Children whose parents or grandparents had known CAD or a genetic lipid disorder should be screened appropriately. Exhaustive lifestyle interventions should be used first with children before pharmacotherapy.18
Along with hypertension, dyslipidemia is a silent killer, tempting patients to become nonadherent. Counseling on adherence and lifestyle modifications must be frequent and emphatic.
Dr. Zanni is a psychologist and health-systems consultant based in Alexandria,Va. Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Bethesda, Md. Views expressed in this article are those of the authors and not those of any government agency.
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