eMedicine Specialties > Endocrinology > Metabolic Disorders

High HDL Cholesterol (Hyperalphalipoproteinemia): Differential Diagnoses & Workup

Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI, Director, Suncoast Cardiovascular Center; Chair, Cardiology Division and Cath Labs, Department of Medicine, Bayfront Medical Center; Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine
Coauthor(s): Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Contributor Information and Disclosures

Updated: Oct 17, 2008

Differential Diagnoses

Primary Biliary Cirrhosis

Other Problems to Be Considered

Longevity syndrome
Familial hyperalphalipoproteinemia (HALP)
Primary HALP
CETP deficiency
LCAT overexpression
Frequent and vigorous sustained aerobic exercise
Heavy alcohol consumption
Use of oral unopposed estrogens
Use of high-dose nicotinic acid
Use of phenytoin
Treatment with fibrates (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)
Treatment with statins
Juvenile corneal opacification
Multiple systemic lipomatosis

Workup

Laboratory Studies

  • Plasma fasting lipid profile
    • Plasma fasting lipid profile measures low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, and triglyceride levels.
    • Lipids in plasma and in isolated lipoprotein fractions are quantified by enzymatic methods. HDL cholesterol levels are determined using a phosphotungstic/magnesium chloride reagent to precipitate the apo B–containing lipoproteins; cholesterol is enzymatically measured in the supernatant. LDL cholesterol levels are calculated using the Friedewald formula or may be measured directly using enzymatic methods.
  • Plasma HDL apolipoproteins
    • Studies of HDL apolipoproteins are not routinely performed clinically, but they may be useful research assays. Some clinicians use ratios of apo A-I to apo B-100 for risk assessment, but these measurements are quite expensive and have proven to be no more accurate than the measurement of the ratio of total cholesterol to HDL cholesterol. Measurement of apo C, apo D, and apo E concentrations is not clinically useful.
    • Apo A lipoproteins include apo A-I, apo A-II, and apo A-IV.
    • Apo C lipoproteins include apo C-I, apo C-II, and apo C-III.
  • Other apolipoproteins include apo D and apo E.

Imaging Studies

  • Whether or not imaging studies are appropriate depends on the clinical manifestations associated with hyperalphalipoproteinemia (HALP), if any.
  • Patients with corneal opacification may require ophthalmoscopic examination and corneal or intraocular imaging.

Other Tests

  • Studies to assess CTEP or hepatic lipase activity are not routinely performed clinically, but they may be useful research assays.
  • Density ultracentrifugation can be used to isolate and measure high-density lipoprotein (HDL) levels directly.
  • Nuclear magnetic resonance measurements of HDL levels are used in some specialized laboratories.
  • HDL2 and HDL3 subfraction measurements can also be performed in the specialized laboratories involved in research studies.

Procedures

  • No procedures are usually required.

Histologic Findings

In rare cases of hyperalphalipoproteinemia in which patients have multiple lipomatosis syndrome, histologic examinations may be performed on biopsy specimens. The findings are usually consistent with lipoma.

More on High HDL Cholesterol (Hyperalphalipoproteinemia)

Overview: High HDL Cholesterol (Hyperalphalipoproteinemia)
Differential Diagnoses & Workup: High HDL Cholesterol (Hyperalphalipoproteinemia)
Treatment & Medication: High HDL Cholesterol (Hyperalphalipoproteinemia)
Follow-up: High HDL Cholesterol (Hyperalphalipoproteinemia)
References
Further Reading
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References

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  2. Ron D, Aviram M, Brook JG. High density lipoprotein in octogenarians. Biochem Med. Oct 1983;30(2):253-60. [Medline].

  3. Yamashita S, Maruyama T, Hirano K, et al. Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia. Atherosclerosis. 2000;152(2):271-85. [Medline].

  4. Miller M. Raising an isolated low HDL-C level: why, how, and when?. Cleve Clin J Med. Jun 2003;70(6):553-60. [Medline].

  5. Kakafika A, Athyros VG, Tziomalos K, et al. High density lipoprotein cholesterol and statin trials. Curr Med Chem. 2008;15(22):2265-70. [Medline].

  6. Bermúdez V, Cano R, Cano C, et al. Pharmacologic management of isolated low high-density lipoprotein syndrome. Am J Ther. Jul-Aug 2008;15(4):377-88. [Medline].

  7. Mendoza S, Lutmer RF, Glueck CJ. Composition of HDL-2 and HDL-3 in familial hyperalphalipoproteinemia. Atherosclerosis. Oct 1976;25(1):131-6. [Medline].

  8. Sich D, Saïdi Y, Giral P, et al. Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity. Metabolism. Aug 1998;47(8):965-73. [Medline].

  9. Arai T, Tsukada T, Murase T, et al. Particle size analysis of high density lipoproteins in patients with genetic cholesteryl ester transfer protein deficiency. Clin Chim Acta. 2000;301(1-2):103-17. [Medline].

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  14. Márquez Contreras E, Casado Martínez JJ, Sánchez Ramos JL, et al. [Prevalence of hyperalphalipoproteinemia in the general population]. Med Clin (Barc). May 8 1993;100(18):699-701. [Medline].

  15. Kucharska-Newton AM, Rosamond WD, Mink PJ, et al. HDL-cholesterol and incidence of breast cancer in the ARIC cohort study. Ann Epidemiol. Sep 2008;18(9):671-7. [Medline].

  16. Deiana L, Pes GM, Carru C, et al. Extremely high HDL levels in a patient with multiple symmetric lipomatosis. Clin Chim Acta. Dec 31 1993;223(1-2):143-7. [Medline].

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  21. Gehrisch S, Kostka H, Tiebel M, et al. Mutations of the human hepatic lipase gene in patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in patients with familial combined hyperlipidemia. J Mol Med. 1999;77(10):728-34. [Medline].

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Keywords

High HDL cholesterol, cholesterol, HDL cholesterol, hyperalphalipoproteinemia, high-density lipoprotein, HDL, low-density lipoprotein, LDL, hypoalphalipoproteinemia, triglycerides, HALP, elevated high-density lipoprotein cholesterol, cholesterol levels, cholesterol level, cholesterol blood, longevity syndrome, familial hyperalphalipoproteinemia, FHALP, hyperlipoproteinemia, hypercholesterolemia, cholesteryl ester transfer protein, CETP, CETP deficiency, high cholesterol, cardioprotection, good cholesterol, heart disease risk, heart disease prevention, CAD prevention, CHD prevention, atherosclerosis prevention, heart disease, CAD, coronary artery disease, coronary heart disease, atherosclerosis

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Contributor Information and Disclosures

Author

Vibhuti N Singh, MD, MPH, FACC, FSCAI, Director, Suncoast Cardiovascular Center; Chair, Cardiology Division and Cath Labs, Department of Medicine, Bayfront Medical Center; Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine
Vibhuti N Singh, MD, MPH, FACC, FSCAI is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, and Florida Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Ghassem Pourmotabbed, MD†, Former Associate Professor, Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Tennessee School of Medicine and Health Science Center
Ghassem Pourmotabbed, MD† is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics
Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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