High HDL Cholesterol (Hyperalphalipoproteinemia) Clinical Presentation

Updated: Aug 06, 2019
  • Author: Basma Abdulhadi, MD; Chief Editor: George T Griffing, MD  more...
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Presentation

History

Hyperalphalipoproteinemia (HALP) has no specific symptoms. It is usually identified through the routine assessment of a lipid profile. Another member of a patient's family may have been found to have elevated high-density lipoprotein (HDL) cholesterol levels. Aside from its cardioprotective role, HALP is occasionally associated with the following symptoms and signs:

  • Juvenile corneal opacification

  • Multiple symmetric lipomatosis [31]

  • History related to secondary causes

    • History of alcohol abuse

    • Treatment with medications such as oral estrogens, statins, niacin (ie, nicotinic acid), phenytoin, or fibrates (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil) [11, 13]

    • History of vigorous, sustained aerobic exercise (eg, long-distance running)

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Physical

Patients with asymptomatic hyperalphalipoproteinemia (HALP) do not present with any significant physical findings. Rare patients may exhibit the following:

  • Juvenile corneal opacification - This is described in patients with marked HALP.

  • Multiple systemic lipomatosis - In rare cases, the development of multiple lipomas has been reported.

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Causes

Causes of hyperalphalipoproteinemia (HALP) may be primary or acquired (secondary). Primary factors can include familial syndromes of elevated high-density lipoprotein (HDL) cholesterol levels, which in some cases may be associated with a decreased risk for coronary artery disease .

  • Primary causes

    • Familial HALP - Familial HALP includes CETP deficiency, familial hepatic lipase deficiency, and primary HALP. A selective up-regulation of apo A-I production is one metabolic cause of familial HALP and leads to high plasma concentrations of HDL cholesterol, apo A-I, and lipoprotein A-I. It possibly may also result in protection from atherosclerotic coronary heart disease (CHD). [32, 33] Familial HALP can involve premature corneal opacity, reduced hepatic lipase activity, and reduced uptake of HDL by lymphocytes.

    • Primary HALP - This is a term used for familial elevated HDL cholesterol levels that are not due to CETP deficiency. Epidemiologic studies have suggested that this syndrome is associated with a decreased risk for coronary artery disease and with increased longevity.

    • CETP deficiency - This asymptomatic, hereditary syndrome is caused by low CETP levels. Decreased CETP activity slows the transport of cholesteryl esters from HDL to apo B–containing lipoproteins. The condition is frequently observed in Japanese Americans. Clinical features include marked elevations of plasma HDL cholesterol in homozygotes (usually >100 mg/dL) and probably lower rates of CHD. In heterozygotes, the HDL levels are only moderately elevated. CETP deficiency has not yet been demonstrated to be associated with a decreased risk for atherosclerotic cardiovascular disease, and some experts do not consider this condition protective against cardiovascular disease. [34]

    • LCAT overexpression - Rarely, HALP has been reported to be due to LCAT overexpression. The activity of LCAT is increased in blood plasma and is associated with high levels of HDL. Reduction in the fractional catabolic rate of HDL is considered to be the predominant mechanism by which LCAT overexpression modulates HDL concentrations. Such patients may have reduced risk of developing CHD.

    • Up-regulation of apo A-I production - Selective up-regulation of apo A-I production is another cause of familial HALP. Affected individuals have elevated HDL cholesterol and apo A-I levels. Additionally, many patients have a reduced risk of atherosclerotic CHD.

  • Secondary causes [11, 13]

    • Vigorous and sustained aerobic exercise (eg, long-distance running)

    • Regular, substantial alcohol consumption

    • Treatment with oral estrogens, particularly if not opposed by progestins

    • Treatment with statins

    • Treatment with nicotinic acid (niacin) at doses greater than 1 g/d

    • Treatment with phenytoin

    • Primary biliary cirrhosis

    • Treatment with fibrates (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)

A study by Wakabayashi indicated that LDL cholesterol differs in its sensitivity to alcohol from HDL cholesterol. Dividing subjects into three tertiles based on blood HDL cholesterol levels, the study found that in the first tertile group, HDL cholesterol seemed to have relatively low sensitivity to alcohol, while LDL cholesterol levels in this tertile were clearly lower in alcohol consumers than in nonconsumers. [35]  

A study by Jan et al found HDL cholesterol levels to be positively correlated with weekly exercise durations of both 2.5 hours or more and under 2.5 hours. The correlation in both exercise groups was found to be more significant in males than in females. [36]

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