Rare genetic disorders, including Tangier disease and LCAT (lecithin:cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients but the effect on outcome is unknown. Reductase inhibitors and fibric acid derivatives exert lesser effects. Aggressive LDL reduction is indicated.
In the presence of hypertriglyceridemia, HDL cholesterol is low because of exchange of cholesteryl esters from HDL into triglyceride-rich lipoproteins. Treatment of the hypertriglyceridemia increases the HDL-C level.
Before primary disorders can be diagnosed, secondary causes of the phenotype must be considered. The more common conditions are summarized in Table 35–2. The lipoprotein abnormality usually resolves if the underlying disorder can be treated successfully. These secondary disorders can also aggravate a primary genetic disorder.
Dietary measures are initiated first—unless the patient has evident coronary or peripheral vascular disease—and may obviate the need for drugs. Patients with the familial hypercholesterolemias always require drug therapy in addition to diet. Cholesterol and saturated and trans-fats are the principal factors that increase LDL.
Total fat, sucrose, and especially fructose increase 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 conclusion 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 7%, and cholesterol to less than 200 mg/d. Reductions in serum cholesterol range from 10% to 20% on this regimen. Use of complex carbohydrates 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 triglycerides.
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 containing ethyl esters of omega-3 fatty acids. 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 (combined) daily. It is important to select preparations free of mercury and other contaminants. 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 essential fatty acids), and fat-soluble vitamins should be given.