Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Low HDL Cholesterol (Hypoalphalipoproteinemia) Medication

  • Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI; Chief Editor: George T Griffing, MD  more...
 
Updated: Jun 19, 2013
 

Medication Summary

Currently, clinical trial results suggest that raising high-density lipoprotein (HDL) levels reduces risk. However, the evidence does not support a recommendation of therapy for hypoalphalipoproteinemia (HA). Additionally, drugs available for cholesterol management do not raise HDL cholesterol levels as much as desired. However, physicians should pay reasonable attention to low HDL cholesterol levels and their management.

According to NCEP ATP III guidelines, the primary goal of therapy is to lower low-density lipoprotein (LDL) cholesterol levels.[2, 3, 4, 5] Once the LDL target has been reached, emphasize therapeutic lifestyle changes, such as weight management and increased exercise, especially if the patient has a metabolic syndrome.

If triglyceride (TG) levels are lower than 200 mg/dL (ie, isolated HA), drugs for raising HDL (eg, fibrates, nicotinic acid) can be considered. Statins have only a modest effect. Treatment for isolated low HDL cholesterol levels is reserved mostly for individuals with established coronary heart disease (CHD) and for patients with risk factors for CHD.

Next

Antilipemic agents

Class Summary

These medications usually lower low-density lipoprotein (LDL) cholesterol levels. In addition, they sometimes lower triglyceride (TG) levels and may modestly elevate high-density lipoprotein (HDL) cholesterol levels. Antilipemic agents may be of value to patients with hypoalphalipoproteinemia (HA).

Niacin, nicotinic acid (Niacor, Nicobid, Nicolar, Niaspan)

 

Source of niacin used in tissue respiration, lipid metabolism, and glycogenolysis. Nicotinic acid has lipid-lowering properties, but nicotinamide and niacinamide do not.

Gemfibrozil (Lopid)

 

Fibric acid antilipemic agent that effectively reduces serum TGs and favorably alters lipoprotein levels; the mechanism of action is unknown, but gemfibrozil may inhibit lipolysis, the secretion of VLDL, and hepatic fatty acid uptake.

Fenofibrate (Tricor)

 

Fibric acid antilipemic agent that lowers LDL cholesterol more effectively than do older fibrates (ie, clofibrate, gemfibrozil). Fenofibrate is primarily indicated for TG reduction and for use in mixed dyslipidemia. This agent increases plasma catabolism and the clearance of TG-rich particles by lipoprotein lipase induction and the suppression of the hepatic production of apo C-III through the activation of PPARs. Fenofibrate activates acetyl-CoA and other enzymes, increasing fatty acid oxidation. TG production is also decreased via the inhibition of acetyl-CoA carboxylase and fatty acid synthase. Clinically, a marked reduction in plasma TGs and VLDL is observed, as is an increase in HDL cholesterol levels.

Previous
Next

HMG-CoA reductase inhibitors

Class Summary

Statins are used to lower LDL cholesterol, but they also modestly raise HDL cholesterol.

Atorvastatin (Lipitor)

 

Selective competitive inhibition of HMG-CoA reductase decreases cholesterol synthesis and increases cholesterol metabolism. Atorvastatin may modestly elevate HDL cholesterol levels. Clinically, reduced levels of circulating total cholesterol, LDL cholesterol, and serum TGs are observed.

Simvastatin (Zocor)

 

Inhibits HMG-CoA reductase, which, in turn, inhibits cholesterol synthesis and increases cholesterol metabolism.

Pravastatin (Pravachol)

 

Competitively inhibits HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol synthesis. Before initiating therapy, place patients on a cholesterol-lowering diet for 3-6 mo, and continue the diet indefinitely.

Lovastatin (Mevacor)

 

Competitively inhibits HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol synthesis. Before initiating therapy, place patients on a cholesterol-lowering diet for 3-6 mo, and continue the diet indefinitely.

Fluvastatin (Lescol)

 

Synthetically prepared HMG-CoA reductase inhibitor with some similarities to lovastatin, simvastatin, and pravastatin. However, fluvastatin is structurally distinct and has a different biopharmaceutical profile (eg, no active metabolites, extensive protein binding, minimal CSF penetration).

Rosuvastatin (Crestor)

 

Competitively inhibits HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol synthesis.

Pitavastatin (Livalo)

 

HMG-CoA reductase inhibitor (statin) indicated for primary or mixed hyperlipidemia. In clinical trials, 2 mg/d reduced total cholesterol and LDL cholesterol similar to atorvastatin 10 mg/d and simvastatin 20 mg/d.

Previous
 
 
Contributor Information and Disclosures
Author

Vibhuti N Singh, MD, MPH, FACC, FSCAI Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine; Director, Cardiology Division and Cardiac Catheterization Lab, Chair, Department of Medicine, Bayfront Medical Center, Bayfront Cardiovascular Associates; President, Suncoast Cardiovascular Research

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, Florida Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Ghassem Pourmotabbed, MD, MD 

Ghassem Pourmotabbed, MD, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Endocrine Society

Disclosure: Nothing to disclose.

References
  1. Yamakawa-Kobayashi K, Yanagi H, Fukayama H, et al. Frequent occurrence of hypoalphalipoproteinemia due to mutant apolipoprotein A-I gene in the population: a population-based survey. Hum Mol Genet. 1999 Feb. 8(2):331-6. [Medline]. [Full Text].

  2. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001 May 16. 285(19):2486-97. [Medline].

  3. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). May 2001. Available at http://www.nhlbi.nih.gov/guidelines/cholesterol/.

  4. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13. 110(2):227-39. [Medline]. [Full Text].

  5. Singh VN. New ATP III lipid guidelines update for patients at high risk for cardiovascular events. Medscape Reference Feature Series - Lipid Newsletter. Jul 21, 2005. series 1(9):[Full Text].

  6. Dioguardi N, Vergani C. [Familial alpha lipoprotein deficiency. Tangier disease, familial hypoalphalipoproteinemia and familial deficiency of lecithin cholesterol acyltransferase deficiency]. Minerva Med. 1983 Mar 24. 74(12):585-94. [Medline].

  7. Sorrenson B, Suetani RJ, Bickley VM, George PM, Williams MJ, Scott RS, et al. An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalipoproteinemia pedigree with three ABCA1 mutations. Biochem Biophys Res Commun. 2011 Jun 10. 409(3):400-5. [Medline].

  8. Chien KL, Chen MF, Hsu HC, et al. Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population. Clin Chim Acta. 2008 Feb. 388(1-2):78-83. [Medline].

  9. van den Bogaard B, Holleboom AG, Duivenvoorden R, Hutten BA, Kastelein JJ, Hovingh GK, et al. Patients with low HDL-cholesterol caused by mutations in LCAT have increased arterial stiffness. Atherosclerosis. 2012 Dec. 225(2):481-5. [Medline].

  10. Savel J, Lafitte M, Pucheu Y, Pradeau V, Tabarin A, Couffinhal T. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship--a review of LCAT deficiency. Vasc Health Risk Manag. 2012. 8:357-61. [Medline]. [Full Text].

  11. Asztalos BF, Schaefer EJ, Horvath KV, et al. Role of LCAT in HDL remodeling: investigation of LCAT deficiency states. J Lipid Res. 2007 Mar. 48(3):592-9. [Medline]. [Full Text].

  12. Tietjen I, Hovingh GK, Singaraja R, Radomski C, McEwen J, Chan E, et al. Increased self-reported risk of coronary artery disease in Caucasians with extremely low HDL cholesterol due to mutations in ABCA1, APOA1, and LCAT. Biochim Biophys Acta. 2011 Aug 19. [Medline].

  13. Santamarina-Fojo S, Hoeg JM, Assmann G. Lecithin cholesterol acyltransferase deficiency and fish eye disease. Scriver CR, Sly WS, Childs B, et al, eds. Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. vol 2: 2817-33.

  14. Asada S, Kuroda M, Aoyagi Y, Bujo H, Tanaka S, Konno S, et al. Disturbed apolipoprotein A-I-containing lipoproteins in fish-eye disease are improved by the lecithin:cholesterol acyltransferase produced by gene-transduced adipocytes in vitro. Mol Genet Metab. 2011 Feb. 102(2):229-31. [Medline].

  15. Uehara Y, Tsuboi Y, Zhang B, et al. POPC/apoA-I discs as a potent lipoprotein modulator in Tangier disease. Atherosclerosis. 2008 Mar. 197(1):283-9. [Medline].

  16. Assmann G, von Eckardstein A, Brewer HB Jr. Familial analphalipoproteinemia: Tangier disease. Scriver CR, Sly WS, Childs B, et al, eds. Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. Vol 2: 2937-60.

  17. Herbert PN, Assmann G, Gotto AM Jr, et al. Familial lipoprotein deficiency (abetalipoproteinemia and Tangier disease). Stanbury JB, Wyngaarden JB, Fredrickson DS, et al, eds. The Metabolic Basis of Inherited Disease. New York, NY: McGraw-Hill; 1982.

  18. Brites FD, Bonavita CD, De Geitere C, et al. Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels. Atherosclerosis. 2000 Sep. 152(1):181-92. [Medline].

  19. Satta MA, Scoppola A, Melina D, et al. [The relationship between high-density lipoproteins, thromboxane B2 and arteriosclerosis in a case of primary hypoalphalipoproteinemia]. Minerva Med. 1989 Dec. 80(12):1345-9. [Medline].

  20. DeLong DM, DeLong ER, Wood PD, et al. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol. The Lipid Research Clinics Prevalence Study. JAMA. 1986 Nov 7. 256(17):2372-7. [Medline].

  21. Ordovas JM, Schaefer EJ, Salem D, et al. Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. N Engl J Med. 1986 Mar 13. 314(11):671-7. [Medline].

  22. Frohlich J, Westerlund J, Sparks D, et al. Familial hypoalphalipoproteinemias. Clin Invest Med. 1990 Aug. 13(4):202-10. [Medline].

  23. Godin DV, Garnett ME, Hoag G, et al. Erythrocyte abnormalities in a hypoalphalipoproteinemia syndrome resembling fish eye disease. Eur J Haematol. 1988 Aug. 41(2):176-81. [Medline].

  24. Rader DJ, deGoma EM. Approach to the patient with extremely low HDL-cholesterol. J Clin Endocrinol Metab. 2012 Oct. 97(10):3399-407. [Medline]. [Full Text].

  25. Barkowski RS, Frishman WH. HDL metabolism and CETP inhibition. Cardiol Rev. 2008 May-Jun. 16(3):154-62. [Medline].

  26. Barter PJ, Brewer HB Jr, Chapman MJ, et al. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003 Feb 1. 23(2):160-7. [Medline]. [Full Text].

  27. de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 2002 May 7. 105(18):2159-65. [Medline]. [Full Text].

  28. Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5. 290(17):2292-300. [Medline]. [Full Text].

  29. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998 Aug 19. 280(7):605-13. [Medline]. [Full Text].

  30. Lamon-Fava S, Postfai B, Diffenderfer M, et al. Role of the estrogen and progestin in hormonal replacement therapy on apolipoprotein A-I kinetics in postmenopausal women. Arterioscler Thromb Vasc Biol. 2006 Feb. 26(2):385-91. [Medline]. [Full Text].

  31. Eslick GD, Howe PR, Smith C, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2008 Sep 5. [Medline].

  32. Vega GL, Grundy SM. Comparison of lovastatin and gemfibrozil in normolipidemic patients with hypoalphalipoproteinemia. JAMA. 1989 Dec 8. 262(22):3148-53. [Medline].

  33. HDL-Atherosclerosis Treatment Study (HATS). Cardiosource: American College of Cardiology. Available at http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=486. Accessed: 2/10/09.

  34. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 (ARBITER 2). Cardiosource: American College of Cardiology. Available at http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=1144. Accessed: 2/10/09.

  35. Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007 Nov 22. 357(21):2109-22. [Medline]. [Full Text].

  36. Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis inpatients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5. 290(17):2292-300. [Medline]. [Full Text].

  37. Parolini C, Marchesi M, Lorenzon P, et al. Dose-related effects of repeated ETC-216 (recombinant apolipoprotein A-I Milano/1-palmitoyl-2-oleoyl phosphatidylcholine complexes) administrations on rabbit lipid-rich soft plaques: in vivo assessment by intravascular ultrasound and magnetic resonance imaging. J Am Coll Cardiol. 2008 Mar 18. 51(11):1098-103. [Medline].

  38. Ibanez B, Vilahur G, Cimmino G, et al. Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J Am Coll Cardiol. 2008 Mar 18. 51(11):1104-9. [Medline].

  39. Ahumada Ayala M, Jimenez Villanueva C, Cardoso Saldana G, et al. [Hypoalphalipoproteinemia and atherosclerosis. Genetic and biochemical profile of 10 families]. Arch Inst Cardiol Mex. 1989 Jan-Feb. 59(1):9-18. [Medline].

  40. Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011 Dec 15. 365(24):2255-67. [Medline].

  41. Daum U, Leren TP, Langer C, et al. Multiple dysfunctions of two apolipoprotein A-I variants, apoA- I(R160L)Oslo and apoA-I(P165R), that are associated with hypoalphalipoproteinemia in heterozygous carriers. J Lipid Res. 1999 Mar. 40(3):486-94. [Medline]. [Full Text].

  42. Dioguardi N. [Familial hypoalphalipoproteinemia. Vergani's disease]. Minerva Med. 1983 Nov 16. 74(44):2659-64. [Medline].

  43. Hersberger M, von Eckardstein A. Low high-density lipoprotein cholesterol: physiological background, clinical importance and drug treatment. Drugs. 2003. 63(18):1907-45. [Medline].

  44. Jones PJ, Ntanios FY, Raeini-Sarjaz M, et al. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr. 1999 Jun. 69(6):1144-50. [Medline].

  45. Kort EN, Ballinger DG, Ding W, et al. Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23. Am J Hum Genet. 2000 Jun. 66(6):1845-56. [Medline]. [Full Text].

  46. Meco JF, Pinto X, Quintana E, et al. [Efficacy of hygienic and dietary therapy in coronary patients with isolated hypoalphalipoproteinemia]. An Med Interna. 1999 Dec. 16(12):620-5. [Medline].

  47. Mingpeng S, Zongli W. The protective role of high-density lipoproteins in atherosclerosis. Exp Gerontol. 1999. 34(4):539-48. [Medline].

  48. Mora S, Buring JE, Ridker PM, Cui Y. Association of high-density lipoprotein cholesterol with incident cardiovascular events in women, by low-density lipoprotein cholesterol and apolipoprotein b100 levels: a cohort study. Ann Intern Med. 2011 Dec 6. 155(11):742-50. [Medline]. [Full Text].

  49. Mott S, Yu L, Marcil M, et al. Decreased cellular cholesterol efflux is a common cause of familial hypoalphalipoproteinemia: role of the ABCA1 gene mutations. Atherosclerosis. 2000 Oct. 152(2):457-68. [Medline].

  50. Rader DJ. High-density lipoproteins as an emerging therapeutic target for atherosclerosis. JAMA. 2003 Nov 5. 290(17):2322-4. [Medline].

  51. Saku K, Zhang B, Shirai K, et al. Hyperinsulinemic hypoalphalipoproteinemia as a new indicator for coronary heart disease. J Am Coll Cardiol. 1999 Nov 1. 34(5):1443-51. [Medline].

  52. Schaefer EJ. Clinical, biochemical, and genetic features in familial disorders of high density lipoprotein deficiency. Arteriosclerosis. 1984 Jul-Aug. 4(4):303-22. [Medline].

  53. Singh VN. Need for more aggressive statin use in various ethnic groups: Latino, Asian, and African American populations. Medscape Reference Feature Series - Lipid Newsletter. Oct 20, 2005. series 1(12):[Full Text].

  54. Singh VN. The USDA "Food Pyramid" needs to go on a diet. Pinellas County Medical Society (PICOMESO) Journal. 2004. 43(4):3, 18-19.

  55. Tall AR. Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. J Clin Invest. 1990 Aug. 86(2):379-84. [Medline]. [Full Text].

  56. Third JL, Montag J, Flynn M, et al. Primary and familial hypoalphalipoproteinemia. Metabolism. 1984 Feb. 33(2):136-46. [Medline].

  57. Zema MJ. Gemfibrozil, nicotinic acid and combination therapy in patients with isolated hypoalphalipoproteinemia: a randomized, open-label, crossover study. J Am Coll Cardiol. 2000. 35(3):640-6. [Medline].

 
Previous
Next
 
Table. Hypoalphalipoproteinemia
Variant Molecular Defect Inheritance Metabolic Defect Lipoprotein Abnormality Clinical Features Premature Atherosclerosis
Familial apo A-I Apo deficiency Autosomal codominant Absent apo A-1 biosynthesis HDL < 5 mg/dL; TGs normal Planar xanthomas, corneal opacities Yes
Familial apo A-I structural mutations Abnormal apo A-I Autosomal dominant Rapid apo A-1 catabolism HDL 15-30 mg/dL; TGs increased Often none; sometimes corneal opacities No
Familial LCAT LCAT deficiency (complete) Autosomal



recessive



Rapid HDL catabolism HDL < 10 mg/dL; TGs increased Corneal opacities, anemia, proteinuria, renal insufficiency No
Fish-eye disease LCAT deficiency (partial) Autosomal recessive Rapid HDL catabolism HDL < 10 mg/dL; TGs increased Corneal opacities No
Tangier disease Unknown Autosomal codominant Very rapid HDL catabolism HDL < 5 mg/dL; TGs usually increased Corneal opacities, enlarged orange tonsils, hepatosplenomegaly, peripheral neuropathy No to yes
Familial HA Unknown Autosomal dominant Usually rapid HDL catabolism HDL 15-35 mg/dL; TGs normal Often none; sometimes corneal opacities No to yes
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.