Hyperlipidemia: Diagnosis and Treatment
The patient's medical and lifestyle history must be taken into account when assessing the lipid profile. Ideally, the patient should be in a steady state (no significant weight change or acute illness). Medications should be noted, since some drugs may interfere with lipid metabolism. Improvement of the conditions listed above that lead to hyperlipidemia may also improve the lipid profile.
Patients must fast for at least 12 hours before blood sampling, because chylomicron clearance can take up to 10 hours. However, a fasted sample is not required for simple cholesterol screening.
Laboratory testing of the lipid profile measures total plasma cholesterol, HDL, and triglycerides directly. VLDL cholesterol levels are calculated by dividing the triglyceride value by 5. LDL cholesterol is calculated by subtracting HDL cholesterol and VLDL cholesterol from total cholesterol. When triglycerides are above 400 mg/dL, LDL calculation is inaccurate, and specialized laboratory tests measuring direct LDL are indicated.
Classification of Lipid Concentrations
Total cholesterol. According to NCEP guidelines, total cholesterol concentrations below 200 mg/dL are "desirable." A borderline high concentration is 200 to 239 mg/dL, and hypercholesterolemia is defined as greater than 240 mg/dL. However, epidemiological evidence suggests that stricter standards may be appropriate. Risk of cardiac events decreases as total cholesterol levels fall until plateauing at a total cholesterol of approximately 150 mg/dL. For children, total cholesterol should be less than 180 mg/dL.
Triglyceride. Normal triglyceride concentration is less than 150 mg/dL. Borderline is 150 to 199 mg/dL, and high is 200 to 499 mg/dL. Concentrations of 500 mg/dL or higher are considered very high.
HDL cholesterol. Concentrations of 60 mg/dL or higher are optimal. In general, an HDL concentration below 40 mg/dL is considered a major risk factor for coronary heart disease (CHD), although women's risk of CHD increases marginally with HDL cholesterol < 50.3 However, HDL is often interpreted in the context of total cholesterol and LDL concentrations, and may be less significant when LDL is low.
LDL cholesterol. According to the NCEP, LDL cholesterol concentrations below 100mg/dL are considered optimal. A range of 100 to129 mg/dL is near optimal. Borderline is 130 to 159 mg/dL. High is 160 to189 mg/dL. However, increasing evidence supports stricter standards, including reductions below 70 mg/dL for very high-risk patients. Studies of hunter-gatherer populations and normal neonates have modified the concept of "normal" cholesterol levels.4 Normal human LDL cholesterol concentration may be as low as 50 to 70 mg/dL, approximately half the US adult population mean. Coronary heart disease risk decreases as LDL cholesterol concentration decreases, reaching a nadir at approximately 40 mg/dL.5 NCEP classification and treatment guidelines have changed to reflect revised normal values and risk estimates.
The mainstay of treatment for hyperlipidemia is dietary and lifestyle modification, followed by drug therapy, as necessary. Hyperlipidemia should not be considered refractory to dietary treatment if the therapeutic regimen included animal products or more than minimal amounts of vegetable oils. Such diets do not lower LDL cholesterol concentrations as effectively as high-fiber, low-fat diets that exclude animal products (see Nutritional Considerations).
Regular exercise can improve lipid concentrations. Low to moderate amounts of physical activity such as walking lower triglyceride concentrations by an average of 10 mg/dL, while raising HDL by 5 mg/dL/ (these numbers are means drawn from large groups). More strenuous activity may have greater effects.6
Patients with familial hypercholesterolemia typically require medication starting in early childhood.
HMG CoA reductase inhibitors (statins) decrease cholesterol production in the liver, and are first-line agents in the treatment of elevated LDL cholesterol. Statins also have important effects on cardiovascular risk aside from their ability to reduce lipid concentrations, and may be indicated for high-risk patients even when lipid targets can be achieved without drug therapy. Potential side effects include myopathy and increased liver enzymes. Some statins may also lower HDL to a below-goal level.
Bile acid sequestrants (eg, cholestyramine, colestipol) are second-line agents for the treatment of elevated LDL cholesterol. These medications can produce gastrointestinal distress, constipation, and impaired absorption of other drugs.
Fibrates (eg, gemfibrozil, fenofibrate) are used as first-line treatment for elevated triglyceride concentrations and may be prescribed in combination with the above drug classes. Gallstones, dyspepsia, and myopathy may occur. Myopathy risk may be particularly high when fibrates are combined with statins.
Nicotinic acid (niacin) is a second-line therapy for all lipid disorders. Niacin is often combined with statins, but is also effective as a single agent. Its use is often limited by skin itching or burning. Other side effects include GI distress, hepatotoxicity, hyperglycemia, and gout.
Ezetimibe and colesevelam decrease GI cholesterol absorption, and have emerged as a favored second-line therapy due to their effectiveness, safety, and lack of side effects. They lower LDL and often raise HDL, and are particularly effective when combined with statins (often achieving lipid targets at lower statin doses). Ezetimibe has emerged as the more effective drug.
Hyperlipidemia: Nutritional Considerations >>