Lipid Abnormalities

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

• Non-HDL cholesterol

  • Increasingly recognized as an important measure of the total quantity of apolipoprotein B–containing atherogenic lipid particles

  • Calculated as Total cholesterol – HDL cholesterol

  • Advantages of non-HDL cholesterol

    • Less sensitive to fasting status

    • Better predictor of cardiovascular risk compared to LDL cholesterol

• Lipoprotein(a)

  • A subfraction of LDL that is largely genetically determined

  • Has been recognized as a casual factor for atherosclerosis

  • May be useful to measure in patients with a strong family history or with early signs of early atherosclerotic cardiovascular disease (ASCVD)

• Assigning a "normal" range for serum lipids can be difficult because mean values vary across the world

  • In Western populations, cholesterol values are about 20% higher than in Asian populations and exceed 300 mg/dL (7.76 mmol/L) in nearly 5% of adults

  • About 10% of adults have LDL cholesterol levels > 200 mg/dL (5.17 mmol/L)

• Familial hypercholesterolemia

  • Genetic disorder

  • Rare in the homozygous state

  • Causes markedly high LDL levels and early cardiovascular disease (CVD)

Demographics

• 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

• No specific symptoms or signs

• Eruptive xanthomas

  • Characterized by red-yellow papules, especially on the buttocks

  • Caused by extremely high levels of chylomicrons or VLDL particles (triglyceride level > 1000 mg/dL or 10 mmol/L)

• Tendinous xanthomas

  • Caused by high LDL concentrations

  • Occur in certain tendinous areas (Achilles, patella, back of the hand)

  • Usually indicate one of the underlying genetic hyperlipidemias

• Lipemia retinalis

  • Characterized by cream-colored blood vessels in the fundus

  • Caused by extremely high triglyceride levels (> 2000 mg/dL or 20 mmol/L)

Differential Diagnosis

• See eTable 28–1