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Current Atherosclerosis Reports

, Volume 4, Issue 1, pp 19–25 | Cite as

Statins in homozygous familial hypercholesterolemia

  • A. D. Marais
  • D. J. Blom
  • J. C. Firth
Article

Abstract

Homozygous familial hypercholesterolemia is a rare disorder resulting in severe premature atherosclerosis. Drug therapy was previously viewed as inadequate for control of the dyslipidemia, so portacaval shunting, plasmapheresis, and liver transplantation were undertaken to treat this condition. Despite these drastic measures, additional cholesterol-lowering treatment may still be required. Furthermore, there is a need for pharmacologic control until additional measures can be undertaken. The statins, an evolving class of cholesterol-modifying drugs, represent a significant development in the treatment of homozygous familial hypercholesterolemia. The experience with statins in this condition is limited, but some insight into their utility has been gained from studies reviewed in this article. It is recommended that high doses of statins be used in combination with other lipid-modifying strategies for the best control of the dyslipidemia of homozygous familial hypercholesterolemia.

Keywords

Atorvastatin Probucol Homozygous Familial Hypercholesterolemia Homozygous Familial Hypercholesterolaemia Avasimibe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References and Recommended Reading

  1. 1.
    Endo A: The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res 1992, 33:1569–1582.PubMedGoogle Scholar
  2. 2.
    Yamamoto A, Sudo H, Endo A: Therapeutic effects of ML-236B in primary hypercholesterolaemia. Atherosclerosis 1980, 35:259–266.PubMedCrossRefGoogle Scholar
  3. 3.
    Uauy R, Vega GL, Grundy SM, Bilheimer DM: Lovastatin therapy in receptor-negative homozygous familial hypercholesterolaemia: lack of effect on low-density lipoprotein concentrations or turnover. J Pediatr 1988, 113:387–392.PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson GR, Ford J, Jenkinson M, Trayner I: Efficacy of mevinolin as adjuvant therapy for refractory familial hypercholesterolaemia. QJM 1986, 232:803–811.Google Scholar
  5. 5.
    Norman D, Sun X, Bourbon M, et al.: Characterization of a novel cellular defect in patients with phenotypic homozygous hypercholesterolaemia. J Clin Invest 1999, 104:619–628.PubMedGoogle Scholar
  6. 6.
    Garcia CK, Wilund K, Arca M, et al.: Autosomal recessive hypercholesterolaemia caused by mutations in a putatative LDL receptor adaptor protein. Science 2001, 292:1310–1312.CrossRefGoogle Scholar
  7. 7.
    Rubinsztein DC, Raal FJ, Seftel HC, et al.: Characterization of six patients who are double hetrozygotes for familial hypercholesterolaemia and familial defective Apo B-100. Arterioscler Thromb Vasc Biol 1993, 13:1076–1081.Google Scholar
  8. 8.
    Benlian P, de Gennes JL, Dairou F, et al.: Phenotypic expression in double heterozygotes for familial hypercholesterolaemia and familial defective apolipoprotein B-100. Hum Mutat 1996, 7:340–345.PubMedCrossRefGoogle Scholar
  9. 9.
    März W, Baumstark MW, Scharnagl H, et al.: Accumulation of “small dense” low density lipoproteins (LDL) in a homozygous patient with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL subfractions with the LDL receptor. J Clin Invest 1993, 92:2922–2933.PubMedCrossRefGoogle Scholar
  10. 10.
    Gallagher JJ, Myant NB: The affinity of low-density lipoproteins and of very-low-density lipoprotein remnants for the low-density lipoprotein receptor in homozygous familial defective apolipoprotein B-100. Atherosclerosis 1995, 115:263–272.PubMedCrossRefGoogle Scholar
  11. 11.
    Goldstein J, Hobbs HH, Brown MS: Familial hypercholesterolaemia. In The Metabolic and Molecular Basis of Inherited Disease. Edited by Scriver A, Beadet W, Sly S, Valle D. New York: McGraw-Hill; 1995:1981–2030.Google Scholar
  12. 12.
    Mahley RW, Ji Z: Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein. Eur J Lipid Res 1999, 40:1–16.Google Scholar
  13. 13.
    Watts GF, Cummings MH, Umpleby M, et al.: Simvastatin decreases the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in heterozygous familial hypercholesterolaemia:pathophysiological and therapeutic implications. Eur J Clin Invest 1995, 25:559–567.PubMedGoogle Scholar
  14. 14.
    Wetterau JR, Gregg RE, Harrity TW, et al.: An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science 1998, 282:751–754.PubMedCrossRefGoogle Scholar
  15. 15.
    Farnier M, Stein E, Megnien S, et al.: Efficacy and Safety of Implitapide, a Microsomal Triglyceride Transfer Protein Inhibitor in Patients with Primary Hypercholesterolemia. XIV International Symposium on Drugs Affecting Lipid Metabolism 2001. New York: Giovanni Lorenzini Medical Foundation; 2001:46.Google Scholar
  16. 16.
    Yamamoto A, Matsuzawa Y, Kishino B, Hayashi R, Kikkawa T: Effects of probucol on homozygous cases of familial hypercholesterolaemia. Atherosclerosis 1983, 48:157–166.PubMedCrossRefGoogle Scholar
  17. 17.
    Baker SG, Joffe BI, Mendelsohn D, Seftel HC: Treatment of homozygous familial hypercholesterolaemia with probucol. S Afr Med J 1982, 62:7–11.PubMedGoogle Scholar
  18. 18.
    Starzl TE, Chase P, Ahrens EH, et al.: Portocaval shunt in patients with familial hypercholesterolemia. Ann Surg 1983, 198:273–283.PubMedGoogle Scholar
  19. 19.
    Issa JS, Garrido A, Giannini SD, et al.: Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery. Arq Bras Cardiol 2000, 75:54–58.CrossRefGoogle Scholar
  20. 20.
    Grossman M, Raper SE, Kozarsky K, et al.: Sucessful ex vivo gene therapy directed to the liver in a patient with familial hypercholesterolaemia. Nature Genet 1994, 6:335–341.PubMedCrossRefGoogle Scholar
  21. 21.
    Marais AD, Wood L, Firth JC, Hall JM, Jacobs P: Plasma exchange for homozygous familial hypercholesterolaemia: the Cape Town experience. Transf Sci 1993, 14:239–247.CrossRefGoogle Scholar
  22. 22.
    Marais AD, Naoumova RP, Firth JC, et al.: Decreased production of low density lipoprotein by atorvastatin after apharesis in homozygous familial hypercholesterolaemia. J Lipid Res 1997, 38:2071–2078.PubMedGoogle Scholar
  23. 23.
    Marais AD, Firth JC, Bateman ME, et al.: Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 1997, 17:1527–1531.PubMedGoogle Scholar
  24. 24.
    Laue L, Hoeg JM, Barnes K, Loriaux L, Chrousos GH: The effects of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway. J Clin Endocrinol Metab 1987, 64:531–535.PubMedCrossRefGoogle Scholar
  25. 25.
    Feher MD, Webb JC, Patel DD, et al.: Cholesterol-lowering drug therapy in a patient with receptor-negative homozygous familial hypercholesterolaemia. Atherosclerosis 1993, 103:171–180.PubMedCrossRefGoogle Scholar
  26. 26.
    Raal FJ, Pilcher GJ, Illingworth DR, et al.: Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis 1997, 135:249–256.PubMedCrossRefGoogle Scholar
  27. 27.
    Tsimihodimos V, Miltiadous G, Elisaf M: Therapy with statins is effective in some patients with homozygous familial hypercholesterolaemia. Atherosclerosis 2000, 153:527.PubMedCrossRefGoogle Scholar
  28. 28.
    Raal FJ, Pappu AS, Illingworth DR, et al.: Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Atherosclerosis 2000, 150:421–428.PubMedCrossRefGoogle Scholar
  29. 29.
    Thiery J, Walli AK, Seidel D: Low-density lipoprotein plasmapharesis with and without lovastatin in the treatment of the homozygous form of familial hypercholesterolaemia. Eur J Pediatr 1990, 149:716–721.PubMedCrossRefGoogle Scholar
  30. 30.
    Palcoux JB, Meyer M, Jouanel P, et al.: Treatment of homozygous familial hypercholesterolaemia by plasma exchange and LDL-apharesis. Transf Sci 1993, 14:423–426.CrossRefGoogle Scholar
  31. 31.
    Ratanjee BD, Raal FJ, Firth JC, Marais AD: Atorvastatin lowers plasma cholesterol in homozygotes for familial hypercholesterolaemia after porto-systemia shunt operations and independently of serum bile acid concentration. Lipid Atherosclerosis Soc S Afr 1998, 23.Google Scholar
  32. 32.
    Klepack E, Raal FJ, Marais AD, Heinonen T: Effects Of Avasimibe in Patients with Severe Hypercholesterolemia.XIV International Symposium on Drugs Affecting Lipid Metabolism 2001. New York: Giovanni Lorenzini Medical Foundation; 2001:107.Google Scholar
  33. 33.
    Gylling H, Miettinen TA: Serum Plant Sterol Levels On and Off Statin Treatment and Stanol vs Sterol Ester Consumption in a Homozygous Form of Familial Hypercholesterolemia.XIV International Symposium on Drugs Affecting Lipid Metabolism 2001. New York: Giovanni Lorenzini Medical Foundation; 2001:31.Google Scholar
  34. 34.
    Seftel HC, Baker SG, Sandler MP, et al.: A host of hypercholesterolaemic homozygotes in South Africa. BMJ 1980, 281:633–636.PubMedCrossRefGoogle Scholar
  35. 35.
    Postiglion A, Montefusco S, Pauciullo P, Mancini M: Effects of atorvasatin in patients with homozygous familial hypercholesterolaemia. Atherosclerosis 1999, 147:423–424.CrossRefGoogle Scholar
  36. 36.
    Yamamoto A, Harada-Shiba M, Kawaguchi A, et al.: The effect of atorvastatin on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy. Atherosclerosis 2000, 153:89–98.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • A. D. Marais
    • 1
  • D. J. Blom
    • 1
  • J. C. Firth
    • 1
  1. 1.Lipid Clinic and Laboratory, Department of Internal MedicineUniversity of Cape Town Health Sciences FacultySouth Africa

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