Erythrocyte-bound Apolipoprotein B After Withdrawal of Statin Therapy

Summary

Background: preliminary data have shown that erythrocyte-bound apolipoprotein B (ery-apoB) may be protective against atherosclerosis. However, statins may have an effect on ery-apoB. Objective: to investigate the effect of statins on ery-apoB levels. Study design: a non-randomized intervention study. Ery-apoB will be measured twice in volunteers who are on statin therapy for medical reasons. After a baseline measurement of ery-apoB volunteers will discontinue their statin use for a period of six weeks followed by a second measurement of ery-apoB. Consecutively subjects will start with their original statin therapy again. Study population: patients on statin therapy aged 18 years or older. Intervention: temporary discontinuation of statin therapy for a period of six weeks. Main study endpoints: changes in ery-apoB levels. Risks, burden and benefits on participation: volunteers will visit the outpatient clinic twice, the second visit will be exactly six weeks after the first visit. The volunteers' general practitioner and medical specialist (internist or cardiologist) will be informed about their participation. Subjects have to fast for 10 hours before every visit and venous blood samples will be drawn on both visits (a total of 36ml of blood). Subjects will discontinue their usual statin therapy for a period of six weeks. No major risks are involved with temporary discontinuation of statin therapy in stable chronic cardiovascular disease. Volunteers will receive 25 euro's in total for participation. Participation serves to further investigate the relation of statins and potentially beneficial binding of apoB on erythrocytes.

Timeline

Start

2012-07

Primary completion

2013-03

Completion

2013-03

Publications

• Background Bovenberg SA, Alipour A, Elte JW, Rietveld AP, Janssen JW, van de Geijn GJ, Njo TN, van Mechelen R, Hervas SM, Cabezas MC. Cell-mediated lipoprotein transport: a novel anti-atherogenic concept. Atheroscler Suppl. 2010 Jun;11(1):25-9. doi: 10.1016/j.atherosclerosissup.2010.04.003. Epub 2010 Apr 27.
• Background Hui DY, Harmony JA. Interaction of plasma lipoproteins with erythrocytes. I. Alteration of erythrocyte morphology. Biochim Biophys Acta. 1979 Feb 2;550(3):407-24. doi: 10.1016/0005-2736(79)90145-7.
• Background Hui DY, Noel JG, Harmony JA. Binding of plasma low density lipoproteins to erythrocytes. Biochim Biophys Acta. 1981 Jun 23;664(3):513-26. doi: 10.1016/0005-2760(81)90129-6.
• Background Bovenberg SA, Klop B, Alipour A, Martinez-Hervas S, Westzaan A, van de Geijn GJ, Janssen HW, Njo T, Birnie E, van Mechelen R, Rietveld AP, Elte JW, Castro Cabezas M. Erythrocyte-associated apolipoprotein B and its relationship with clinical and subclinical atherosclerosis. Eur J Clin Invest. 2012 Apr;42(4):365-70. doi: 10.1111/j.1365-2362.2011.02591.x. Epub 2011 Sep 13.
• Background Molgaard J, von Schenck H, Olsson AG. Effects of simvastatin on plasma lipid, lipoprotein and apolipoprotein concentrations in hypercholesterolaemia. Eur Heart J. 1988 May;9(5):541-51. doi: 10.1093/oxfordjournals.eurheartj.a062541.
• Background Bard JM, Luc G, Douste-Blazy P, Drouin P, Ziegler O, Jacotot B, Dachet C, De Gennes JL, Fruchart JC. Effect of simvastatin on plasma lipids, apolipoproteins and lipoprotein particles in patients with primary hypercholesterolaemia. Eur J Clin Pharmacol. 1989;37(6):545-50. doi: 10.1007/BF00562541.
• Background Klop B, Elte JW, Cabezas MC. [Cholesterol homeostasis and enterohepatic connection: new insights in cholesterol absorption]. Ned Tijdschr Geneeskd. 2011;155:A2503. Dutch.
• Background Poli A. Atorvastatin: pharmacological characteristics and lipid-lowering effects. Drugs. 2007;67 Suppl 1:3-15. doi: 10.2165/00003495-200767001-00002.
• Background Alipour A, van Oostrom AJ, Izraeljan A, Verseyden C, Collins JM, Frayn KN, Plokker TW, Elte JW, Castro Cabezas M. Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):792-7. doi: 10.1161/ATVBAHA.107.159749. Epub 2008 Jan 24.
• Background Jukema JW. [The availability of only one statin is inadequate]. Ned Tijdschr Geneeskd. 2005 Dec 10;149(50):2773-4. Dutch.
• Background Garcia MJ, Reinoso RF, Sanchez Navarro A, Prous JR. Clinical pharmacokinetics of statins. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):457-81.
• Background Pineda A, Cubeddu LX. Statin rebound or withdrawal syndrome: does it exist? Curr Atheroscler Rep. 2011 Feb;13(1):23-30. doi: 10.1007/s11883-010-0148-x.
• Background Janssen SP, Smulders YM, Gerdes VE, Visseren FL. [Muscle problems due to statins: underestimated]. Ned Tijdschr Geneeskd. 2010;154:A1684. Dutch.
• Background Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004816. doi: 10.1002/14651858.CD004816.pub4.
• de Vries MA, Alipour A, Klop B, van de Geijn GJ, Janssen HW, Njo TL, van der Meulen N, Rietveld AP, Liem AH, Westerman EM, de Herder WW, Cabezas MC. Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls. Metabolism. 2015 Feb;64(2):213-7. doi: 10.1016/j.metabol.2014.10.011. Epub 2014 Oct 16.

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