Low HDL Cholesterol (Hypoalphalipoproteinemia) Clinical Presentation

Updated: Nov 03, 2016
  • Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI; Chief Editor: George T Griffing, MD  more...
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Persons with low high-density lipoprotein (HDL) cholesterol levels, except those patients with a deficiency syndrome, have no symptoms specific to the condition. However, they may have a history of premature atherosclerosis, as well as a history consistent with coronary heart disease (CHD), peripheral artery disease, or other such conditions.

  • Premature atherosclerosis

    • CHD - A history of angina or myocardial infarction (MI) in a person below age 60 years, a history of premature heart disease in a patient's siblings and first-degree relatives, sequelae of MI

    • Congestive heart failure

    • Peripheral vascular disease - A history of claudication

  • Cerebrovascular disease

    • History of stroke

    • History of transient ischemic attack

    • History of carotid endarterectomy

  • Xanthomas (tendinous, cutaneous)

  • History consistent with secondary causes

    • Cigarette smoking

    • Physical inactivity

    • Hypertriglyceridemia

    • Renal disease

    • Obesity

    • Medications

    • Androgens

    • Progestins

    • Probucol

    • High-dose thiazides

    • High-dose beta blockers

  • Corneal opacification



Persons with the common low high-density lipoprotein (HDL) syndromes have no specific physical findings. If atherosclerosis is present, the examination may reveal findings consistent with the affected arterial bed. These may include the following:

  • Tendon xanthomas

  • Cutaneous xanthomas

  • Findings of ischemic coronary heart disease or peripheral vascular disease

    • S4 gallop consistent with ischemic left ventricular dysfunction

    • Signs of congestive heart failure, such as a raised jugular distension, crackles at the lung bases, edema, and hepatomegaly

    • Arrhythmias

  • Corneal opacification



Hypoalphalipoproteinemia (HA) may be caused by familial or primary and secondary disorders that are associated with low plasma levels of high-density lipoprotein (HDL) cholesterol.

  • Familial or primary causes - Decreased or absent synthesis of apo A-I due to a gene defect is the cause of apo A-I/apo C-III and apo A-I/apo C-III/apo A-IV deficiency. However, the etiology of the low levels of HDL is unclear for most of the remaining familial HAs. Increased catabolism, decreased synthesis, and altered equilibration of HDL between intravascular and extravascular spaces have all been suggested as underlying causes of low plasma HDL levels. Whatever the cause, these disorders are associated with altered HDL composition and altered equilibration of cholesterol, among the various lipoprotein classes.

    • Familial apo A-I deficiency and structural mutations

    • Familial lecithin-cholesterol acetyltransferase (LCAT) deficiency

    • Tangier disease

    • Miscellaneous

      • Familial HDL deficiency

      • Familial apo A-I and apo C-III deficiency (formerly known as apo A-I absence)

      • Familial deficiency of apo A-I and apo C-III

      • Fish eye disease (partial LCAT deficiency)

      • Familial HA

      • Apo A-I variants (apo A-I Milano, apo A-I Marburg, apo A-I Giessen, apo A-I Munster)

  • Secondary causes

    • Obesity

    • Physical inactivity

    • Type 2 diabetes

    • Cigarette smoking

    • End-stage renal disease

    • Hypertriglyceridemia

    • Probucol

    • Androgens

    • Progestins

    • High-dose thiazide diuretics

    • High-dose beta blockers

    • Very low-fat diet

    • Dysglobulinemia

    • Severe liver disease

    • Malabsorption

    • Malnutrition

    • Severe inflammatory disease

  • Miscellaneous - Data in the literature suggest that some cases of HA involve an increase in thromboxane B2 together with an increased risk of atherosclerosis. Satta and colleagues described a 32-year-old man who revealed clinical and biochemical features strongly indicative of this pathology (see Histologic Findings). [24]