- Hypercholesterolemia, elevated low-density lipoprotein, and low high-density lipoprotein (HDL) are unequivocally linked to increased risk for coronary heart disease (CHD) and cerebrovascular morbidity and mortality; low-density lipoprotein (LDL) is the primary target.
- Multiple genetic abnormalities and environmental factors are involved in clinical lipid abnormalities and routinely used clinical laboratory measurements do not define the underlying abnormalities.
- Initial therapy for any lipoprotein disorder is therapeutic lifestyle changes with restricted intake of total and saturated fat and cholesterol and a modest increase in polyunsaturated fat intake along with a program of regular exercise and weight reduction if needed.
- If therapy is insufficient after therapeutic lifestyle changes, lipid-lowering agents should be chosen based on the specific lipoprotein disorder presentation and the severity of the lipid abnormality.
- Considering compliance, adverse effects, and effectiveness, statins are the drugs of choice for patients with hypercholesterolemia because they are the most potent form of monotherapy and are cost-effective in patients with known coronary artery disease (CAD) or multiple risk factors and in high-risk primary prevention patients.
- Patients not responding to statin monotherapy may be treated with combination therapy for hypercholesterolemia, but should be monitored closely because of an increased risk for adverse effects and drug interactions.
- Hypertriglyceridemia usually responds well to niacin, gemfibrozil, and fenofibrate; high-dose niacin should be used cautiously in diabetics because of worsening glycemic control. Statins lower triglycerides to a variable extent depending on baseline triglyceride concentration and statin potency.
- Low HDL-C is addressed with lifestyle modifications such as smoking cessation and increased exercise; niacin and gemfibrozil and fenofibrate can significantly increase HDL-C as well.
- Lipid-lowering therapy is generally considered to be cost-effective, particularly in secondary intervention and high-risk patients.
- Reductions in elevated total cholesterol and LDL-C reduce CHD mortality and total mortality; increasing HDL may reduce CHD events as well. Aggressive treatment of hypercholesterolemia results in fewer patients progressing to myocardial infarction, angina, and stroke, and reduces the need for interventions such as coronary artery bypass graft and percutaneous transluminal coronary angioplasty.
- Lomitapide and mipomersen have been recently approved for the treatment of homozygous familial hypercholesterolemia. Both have novel mechanisms of action to lower total and LDL cholesterol.
On completion of the chapter, the reader will be able to:
Describe the prevalence of lipid abnormalities (total cholesterol, low-density lipoprotein [LDL] cholesterol, and high-density lipoprotein [HDL] cholesterol) in the United States and trends in lipid concentrations over time and among various racial groups.
Describe how dietary fat and endogenous lipoprotein metabolism are interrelated and the major metabolic pathways for lipoprotein and apolipoprotein synthesis and catabolism.
Outline the pathogenesis of atherosclerotic plaque formation focusing on the roles of adhesion molecules, cytokines, LDL, oxidized LDL, HDL and the triglyceride-rich particles, and very-low-density lipoprotein (VLDL).
List the major lipoprotein disorders associated with abnormalities of chylomicrons, VLDL, LDL, and HDL and relate them to the risk of cardiovascular disease.
Describe the role of lipoprotein analysis in the initial evaluation and long-term management of patients with lipid disorders, and list ...