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Elevated High-Density Lipoprotein Levels (HDL)

By Anne Carol Goldberg, MD, Professor of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine

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Elevated high-density lipoprotein (HDL) level is HDL cholesterol > 80 mg/dL (>2.1 mmol/L).

Elevated HDL cholesterol levels usually correlate with decreased cardiovascular risk; however, high HDL cholesterol levels caused by some genetic disorders may not protect against cardiovascular disease, probably because of accompanying lipid and metabolic abnormalities.

Primary causes of elevated HDL levels are single or multiple genetic mutations that result in overproduction or decreased clearance of HDL. Secondary causes of high HDL cholesterol include all of the following:

  • Chronic alcoholism without cirrhosis

  • Primary biliary cirrhosis

  • Hyperthyroidism

  • Drugs (eg, corticosteroids, insulin, phenytoin)

The unexpected finding of high HDL cholesterol in patients not taking lipid-lowering drugs should prompt a diagnostic evaluation for a secondary cause with measurements of AST, ALT, and thyroid-stimulating hormone; a negative evaluation suggests a possible primary cause.

Cholesteryl ester transfer protein (CETP) deficiency is a rare autosomal recessive disorder caused by a CETP gene mutation. CETP facilitates transfer of cholesterol esters from HDL to other lipoproteins, and CETP deficiency affects low-density lipoprotein (LDL) cholesterol and slows HDL clearance. Affected patients display no symptoms or signs but have HDL cholesterol > 150 mg/dL (> 3.9 mmol/L). Protection from cardiovascular disorders has not been proved. No treatment is necessary.

Familial hyperalphalipoproteinemia is an autosomal dominant condition caused by various unidentified and known genetic mutations, including those that cause apoprotein A-I overproduction and apoprotein C-III variants. The disorder is usually diagnosed incidentally when plasma HDL cholesterol levels are > 80 mg/dL. Affected patients have no other symptoms or signs. No treatment is necessary.