A Study Of The Usage Of Statins In A Community Heart Failure Population

Summary

Inflammation and fibrosis may be important contributors to worsening heart failure. As well as lowering cholesterol, statins are also known to reduce inflammatory markers such as C-reactive protein which are elevated in severe heart failure. Therefore, this project will evaluate the benefit, if any, of statins on markers of heart structure and function, on inflammatory markers and markers of fibrosis in patients with normal cholesterol.

Timeline

Start

2003-05

Primary completion

2005-11

Completion

2008-01

Publications

• Background Cleland JG, Swedberg K, Poole-Wilson PA. Successes and failures of current treatment of heart failure. Lancet. 1998 Aug;352 Suppl 1:SI19-28. doi: 10.1016/s0140-6736(98)90015-0. No abstract available.
• Background Clearfield MB. Statins: balancing benefits, efficacy and safety. Expert Opin Pharmacother. 2002 May;3(5):469-77. doi: 10.1517/14656566.3.5.469.
• Background Braunstein JB, Cheng A, Cohn G, Aggarwal M, Nass CM, Blumenthal RS. Lipid disorders: justification of methods and goals of treatment. Chest. 2001 Sep;120(3):979-88. doi: 10.1378/chest.120.3.979.
• Background Krum H, McMurray JJ. Statins and chronic heart failure: do we need a large-scale outcome trial? J Am Coll Cardiol. 2002 May 15;39(10):1567-73. doi: 10.1016/s0735-1097(02)01827-2.
• Background Kjekshus J. Debate: Statins should be used in patients with heart failure. Curr Control Trials Cardiovasc Med. 2001;2(6):268-270. doi: 10.1186/cvm-2-6-268.
• Background Kronmal RA, Cain KC, Ye Z, Omenn GS. Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993 May 10;153(9):1065-73.
• Background Tavazzi L, Tognoni G, Franzosi MG, Latini R, Maggioni AP, Marchioli R, Nicolosi GL, Porcu M; GISSI-HF Investigators. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004 Aug;6(5):635-41. doi: 10.1016/j.ejheart.2004.03.001.
• Background Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis. Lancet. 2000 Sep 9;356(9233):930-3. doi: 10.1016/S0140-6736(00)02690-8.
• Background Alonso-Martinez JL, Llorente-Diez B, Echegaray-Agara M, Olaz-Preciado F, Urbieta-Echezarreta M, Gonzalez-Arencibia C. C-reactive protein as a predictor of improvement and readmission in heart failure. Eur J Heart Fail. 2002 Jun;4(3):331-6. doi: 10.1016/s1388-9842(02)00021-1.
• Background Gullestad L, Kjekshus J, Damas JK, Ueland T, Yndestad A, Aukrust P. Agents targeting inflammation in heart failure. Expert Opin Investig Drugs. 2005 May;14(5):557-66. doi: 10.1517/13543784.14.5.557.
• Background Riesen WF, Engler H, Risch M, Korte W, Noseda G. Short-term effects of atorvastatin on C-reactive protein. Eur Heart J. 2002 May;23(10):794-9. doi: 10.1053/euhj.2001.2967.
• Background Weber KT, Sun Y, Tyagi SC, Cleutjens JP. Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. J Mol Cell Cardiol. 1994 Mar;26(3):279-92. doi: 10.1006/jmcc.1994.1036.
• Background Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999 Jan;79(1):215-62. doi: 10.1152/physrev.1999.79.1.215.
• Background Bujak M, Ren G, Kweon HJ, Dobaczewski M, Reddy A, Taffet G, Wang XF, Frangogiannis NG. Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling. Circulation. 2007 Nov 6;116(19):2127-38. doi: 10.1161/CIRCULATIONAHA.107.704197. Epub 2007 Oct 22.
• Background Querejeta R, Lopez B, Gonzalez A, Sanchez E, Larman M, Martinez Ubago JL, Diez J. Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation. 2004 Sep 7;110(10):1263-8. doi: 10.1161/01.CIR.0000140973.60992.9A. Epub 2004 Aug 16.
• Background Martos R, Baugh J, Ledwidge M, O'Loughlin C, Conlon C, Patle A, Donnelly SC, McDonald K. Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation. 2007 Feb 20;115(7):888-95. doi: 10.1161/CIRCULATIONAHA.106.638569. Epub 2007 Feb 5.
• Background Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000 Nov 28;102(22):2700-6. doi: 10.1161/01.cir.102.22.2700.
• Background Kapoun AM, Liang F, O'Young G, Damm DL, Quon D, White RT, Munson K, Lam A, Schreiner GF, Protter AA. B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation. Circ Res. 2004 Mar 5;94(4):453-61. doi: 10.1161/01.RES.0000117070.86556.9F. Epub 2004 Jan 15.
• Abulhul E, McDonald K, Martos R, Phelan D, Spiers JP, Hennessy M, Baugh J, Watson C, O'Loughlin C, Ledwidge M. Long-term statin therapy in patients with systolic heart failure and normal cholesterol: effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide. Clin Ther. 2012 Jan;34(1):91-100. doi: 10.1016/j.clinthera.2011.11.002. Epub 2011 Dec 9.

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