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Statins in homozygous familial hypercholesterolemia

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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.

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References and Recommended Reading

  1. Endo A: The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res 1992, 33:1569–1582.

    PubMed  CAS  Google Scholar 

  2. Yamamoto A, Sudo H, Endo A: Therapeutic effects of ML-236B in primary hypercholesterolaemia. Atherosclerosis 1980, 35:259–266.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. Yamamoto A, Matsuzawa Y, Kishino B, Hayashi R, Kikkawa T: Effects of probucol on homozygous cases of familial hypercholesterolaemia. Atherosclerosis 1983, 48:157–166.

    Article  PubMed  CAS  Google Scholar 

  17. Baker SG, Joffe BI, Mendelsohn D, Seftel HC: Treatment of homozygous familial hypercholesterolaemia with probucol. S Afr Med J 1982, 62:7–11.

    PubMed  CAS  Google Scholar 

  18. Starzl TE, Chase P, Ahrens EH, et al.: Portocaval shunt in patients with familial hypercholesterolemia. Ann Surg 1983, 198:273–283.

    PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  26. Raal FJ, Pilcher GJ, Illingworth DR, et al.: Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis 1997, 135:249–256.

    Article  PubMed  CAS  Google Scholar 

  27. Tsimihodimos V, Miltiadous G, Elisaf M: Therapy with statins is effective in some patients with homozygous familial hypercholesterolaemia. Atherosclerosis 2000, 153:527.

    Article  PubMed  CAS  Google Scholar 

  28. Raal FJ, Pappu AS, Illingworth DR, et al.: Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Atherosclerosis 2000, 150:421–428.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

  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. 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. Seftel HC, Baker SG, Sandler MP, et al.: A host of hypercholesterolaemic homozygotes in South Africa. BMJ 1980, 281:633–636.

    Article  PubMed  CAS  Google Scholar 

  35. Postiglion A, Montefusco S, Pauciullo P, Mancini M: Effects of atorvasatin in patients with homozygous familial hypercholesterolaemia. Atherosclerosis 1999, 147:423–424.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Lipid Clinic and Laboratory, Department of Internal Medicine, University of Cape Town Health Sciences Faculty, Anzio Road, Observatory 7925, South Africa

    A. D. Marais MB, ChB, FCP(SA), D. J. Blom MB, ChB, FCP(SA) & J. C. Firth MB, ChB, DCH

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  1. A. D. Marais MB, ChB, FCP(SA)
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  2. D. J. Blom MB, ChB, FCP(SA)
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  3. J. C. Firth MB, ChB, DCH
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Marais, A.D., Blom, D.J. & Firth, J.C. Statins in homozygous familial hypercholesterolemia. Curr Atheroscler Rep 4, 19–25 (2002). https://doi.org/10.1007/s11883-002-0058-7

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