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Key Features

Essentials of Diagnosis

  • Elevated serum total cholesterol or low-density lipoprotein (LDL) cholesterol, low serum high-density lipoprotein (HDL) cholesterol, or elevated serum triglycerides

  • Usually asymptomatic

  • In severe cases associated with metabolic abnormalities, superficial lipid deposition occurs

General Considerations

  • Cholesterol and triglycerides are the two main circulating lipids

  • Elevated levels of LDL cholesterol are associated with increased risk of atherosclerotic heart disease

  • High levels of HDL cholesterol are associated with lower risk of atherosclerotic heart disease

  • The exact mechanism by which LDL and HDL affect atherosclerosis is not fully delineated

  • Familial genetic disorders are an uncommon, but often lethal, cause of elevated cholesterol

  • Familial genetic disorders should be considered in patients who have onset of atherosclerosis in their 20s or 30s


  • More common in men than women before age 50

  • More common in women than men after age 50

  • More common in whites and Hispanics than among blacks

Clinical Findings

Symptoms and Signs

  • Usually asymptomatic

  • Extremely high levels of chylomicrons or very low-density lipoprotein (VLDL) particles are associated with eruptive xanthomas

  • Very high LDL levels are associated with tendinous xanthomas

  • Very high triglycerides (> 2000 mg/dL) are associated with lipemia retinalis (cream-colored vessels in the fundus)

Differential Diagnosis

eTable 28–1.Secondary causes of lipid abnormalities.

  • Idiopathic

  • Hypothyroidism

  • Nephrotic syndrome

  • Chronic kidney disease

  • Obstructive liver disease

  • Diabetes mellitus

  • Anorexia nervosa

  • Cushing syndrome

  • Familial, eg, familial hypercholesterolemia

  • Drugs

    • Oral contraceptives

    • Thiazides (short-term effect)

    • β-Blockers (short-term effect)

    • Corticosteroids

    • Cyclosporine


  • Alcohol

  • Obesity

  • Metabolic syndrome (insulin resistance, low HDL)

  • Diabetes mellitus

  • Chronic kidney disease

  • Lipodystrophy, eg, protease inhibitors

  • Pregnancy

  • Familial

  • Drugs

    • Oral contraceptives

    • Isotretinoin

    • Thiazides (short-term effect)

    • β-Blockers (short-term effect)

    • Corticosteroids

    • Bile-acid binding resins


  • Screen for lipid disorders in

    • Patients with coronary heart disease (CHD), diabetes mellitus, peripheral vascular disease, aortic aneurysm, cerebrovascular disease, chronic renal insufficiency, ...

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