Dyslipidemia: Definition and Pathophysiology

Definition

• Dyslipidemia is defined as abnormal levels of lipids in the blood
• Elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides
• Low levels of high-density lipoprotein (HDL) cholesterol

Pathophysiology

• Cholesterol, triglycerides, and phospholipids are transported in blood as lipoprotein complexes
• Elevated total and LDL cholesterol, and reduced HDL cholesterol, are associated with coronary heart disease (CHD)
• Risk factors, such as oxidized LDL, mechanical injury to the endothelium, and excessive homocysteine, lead to endothelial dysfunction and atherosclerosis
• Eventual clinical outcomes may include angina, myocardial infarction, arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death

Types of Dyslipidemia

• Primary or genetic lipoprotein disorders are classified into six categories:
  • I (chylomicrons)
  • IIa (LDL) - "Isolated hypercholesterolemia" or "Familial hypercholesterolemia"
  • IIb (LDL + VLDL) - "Combined hyperlipidemia"
  • III (intermediate-density lipoprotein - IDL)
  • IV (VLDL) - "Familial hypertriglyceridemia"
  • V (VLDL + chylomicrons)
• Secondary forms of hyperlipidemia may be caused by certain drug classes, such as progestins, thiazide diuretics, glucocorticoids, β-blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, and sirolimus

Clinical Presentation

• Most patients are asymptomatic for many years
• Symptomatic patients may complain of chest pain, palpitations, sweating, anxiety, shortness of breath, abdominal pain, or loss of consciousness or difficulty with speech or movement
• Familial hypercholesterolemia is characterized by a selective elevation in plasma LDL and deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas)

Diagnosis

• A fasting (12 hours or longer) lipoprotein profile, including total cholesterol, LDL, HDL, and triglycerides, should be measured in all adults 20 years or older at least once every 5 years
• A complete history and physical examination should assess cardiovascular risk factors, family history, and secondary causes of dyslipidemia
• Diabetes mellitus and the metabolic syndrome are considered CHD risk equivalents
• Metabolic syndrome is characterized by abdominal obesity, atherogenic dyslipidemia, increased blood pressure, insulin resistance, and prothrombotic and proinflammatory states

Treatment

• The goals of treatment are to lower total and LDL cholesterol and reduce the risk of first or recurrent events, such as myocardial infarction, angina, heart failure, ischemic stroke, and peripheral arterial disease
• The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) recommends a fasting lipoprotein profile and risk factor assessment for initial classification of adults
• Major risk factors include age, family history of premature CHD, cigarette smoking, hypertension, and low HDL cholesterol