Secondary Hyperlipoproteinemia

SECONDARY HYPERLIPOPROTEINEMIA

Before primary disorders can be diagnosed, secondary causes of the phenotype must be considered. The more common conditions are summarized in Table 35–3. The lipoprotein abnormality usu-ally resolves if the underlying disorder can be treated successfully.

DIETARY MANAGEMENT OF HYPERLIPOPROTEINEMIA

Dietary measures are initiated first—unless the patient has evident coronary or peripheral vascular disease—and may obviate the need for drugs. Patients with familial hypercholesterolemia or familial combined hyperlipidemia always require drug therapy. Cholesterol and saturated and trans-fats are the principal factors that increase LDL, whereas total fat, alcohol, and excess calories increase triglycerides.

Sucrose and fructose raise VLDL. Alcohol can cause significant hypertriglyceridemia by increasing hepatic secretion of VLDL. Synthesis and secretion of VLDL are increased by excess calories. During weight loss, LDL and VLDL levels may be much lower than can be maintained during neutral caloric balance. The con-clusion that diet suffices for management can be made only after weight has stabilized for at least 1 month.

General recommendations include limiting total calories from fat to 20–25% of daily intake, saturated fats to less than 8%, and cholesterol to less than 200 mg/d. Reductions in serum cholesterol range from 10% to 20% on this regimen. Use of complex carbo-hydrates and fiber is recommended, and cis-monounsaturated fats should predominate. Weight reduction, caloric restriction, and avoidance of alcohol are especially important for patients with elevated VLDL and IDL.

The effect of dietary fats on hypertriglyceridemia is dependent on the disposition of double bonds in the fatty acids. Omega-3 fatty acids found in fish oils, but not those from plant sources, activate peroxisome proliferator-activated receptor-alpha (PPAR-α) and can induce profound reduction of triglycerides in some patients. They also have anti-inflammatory and antiarrhythmic activities. Omega-3 fatty acids are available over the counter as triglycerides from marine sources or as a prescription medication (Lovaza) containing ethyl esters of omega-3 fatty acids. The rec-ommended dose of Lovaza is 4 g/d. It is necessary to determine the content of docosahexaenoic acid and eicosapentaenoic acid in over-the-counter preparations. Appropriate amounts should be taken to provide up to 3–4 g of these fatty acids daily. It is impor-tant to select preparations free of mercury and other contami-nants. The omega-6 fatty acids present in vegetable oils may cause triglycerides to increase.

Patients with primary chylomicronemia and some with mixed lipemia must consume a diet severely restricted in total fat (10–20 g/d, of which 5 g should be vegetable oils rich in essen-tial fatty acids), and fat-soluble vitamins should be given.

Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Supplementation with folic acid plus other B vita-mins is indicated in severe homocysteinemia.

BASIC & CLINICAL PHARMACOLOGY OF DRUGS USED IN HYPERLIPIDEMIA

The decision to use drug therapy for hyperlipidemia is based on the specific metabolic defect and its potential for causing athero-sclerosis or pancreatitis. Suggested regimens for the principal lipoprotein disorders are presented in Table 35–2. Diet should be continued to achieve the full potential of the drug regimen. These drugs should be avoided in pregnant and lactating women and those likely to become pregnant. All drugs that alter plasma lipo-protein concentrations may require adjustment of doses of warfa-rin and indandione anticoagulants. Children with heterozygous familial hypercholesterolemia may be treated with a resin or reductase inhibitor, usually after 7 or 8 years of age, when myeli-nation of the central nervous system is essentially complete. The decision to treat a child should be based on the level of LDL, other risk factors, the family history, and the child’s age. Drugs are rarely indicated before age 16 in the absence of multiple risk factors or compound genetic dyslipidemias.