Effect of ACE-inhibitors on Aortic Stiffness in Elderly Patients With Chronic Kidney Disease

Summary

The goal of this proposal is to investigate the potential for ACE-inhibitors (ACE-I)(drugs primarily used to treat hypertension or congestive heart failure) to prevent or delay cardiovascular disease (CVD) in older adults with chronic kidney disease (CKD) by examining their impact on aortic stiffness in people with stage 3 CKD in a randomized, controlled study.

Timeline

Start

2009-01

Primary completion

2009-12

Completion

2011-12

Publications

• Background Ryan TP, Sloand JA, Winters PC, Corsetti JP, Fisher SG. Chronic kidney disease prevalence and rate of diagnosis. Am J Med. 2007 Nov;120(11):981-6. doi: 10.1016/j.amjmed.2007.05.012.
• Background Foley RN, Parfrey PS. Cardiovascular disease and mortality in ESRD. J Nephrol. 1998 Sep-Oct;11(5):239-45.
• Background Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001 Oct;38(4):938-42. doi: 10.1161/hy1001.096358.
• Background Covic A, Haydar AA, Bhamra-Ariza P, Gusbeth-Tatomir P, Goldsmith DJ. Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients. J Nephrol. 2005 Jul-Aug;18(4):388-96.
• Background London GM, Marchais SJ, Guerin AP. Arterial stiffness and function in end-stage renal disease. Adv Chronic Kidney Dis. 2004 Apr;11(2):202-9. doi: 10.1053/j.arrt.2004.02.008.
• Background Wang MC, Tsai WC, Chen JY, Huang JJ. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am J Kidney Dis. 2005 Mar;45(3):494-501. doi: 10.1053/j.ajkd.2004.11.011.
• Background Kundhal K, Lok CE. Clinical epidemiology of cardiovascular disease in chronic kidney disease. Nephron Clin Pract. 2005;101(2):c47-52. doi: 10.1159/000086221. Epub 2005 Jun 7.
• Background Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, Jeppesen J. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006 Feb 7;113(5):664-70. doi: 10.1161/CIRCULATIONAHA.105.579342.
• Background London GM, Guerin AP, Marchais SJ, Pannier B, Safar ME, Day M, Metivier F. Cardiac and arterial interactions in end-stage renal disease. Kidney Int. 1996 Aug;50(2):600-8. doi: 10.1038/ki.1996.355.
• Background Shinohara K, Shoji T, Tsujimoto Y, Kimoto E, Tahara H, Koyama H, Emoto M, Ishimura E, Miki T, Tabata T, Nishizawa Y. Arterial stiffness in predialysis patients with uremia. Kidney Int. 2004 Mar;65(3):936-43. doi: 10.1111/j.1523-1755.2004.00468.x.
• Background Safar ME, London GM, Plante GE. Arterial stiffness and kidney function. Hypertension. 2004 Feb;43(2):163-8. doi: 10.1161/01.HYP.0000114571.75762.b0. Epub 2004 Jan 19.
• Background Dao HH, Essalihi R, Bouvet C, Moreau P. Evolution and modulation of age-related medial elastocalcinosis: impact on large artery stiffness and isolated systolic hypertension. Cardiovasc Res. 2005 May 1;66(2):307-17. doi: 10.1016/j.cardiores.2005.01.012.
• Background Ferrari AU, Radaelli A, Centola M. Invited review: aging and the cardiovascular system. J Appl Physiol (1985). 2003 Dec;95(6):2591-7. doi: 10.1152/japplphysiol.00601.2003.
• Background Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, Vasan RS, Levy D. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension. 2004 Jun;43(6):1239-45. doi: 10.1161/01.HYP.0000128420.01881.aa. Epub 2004 May 3.
• Background Sawabe M, Takahashi R, Matsushita S, Ozawa T, Arai T, Hamamatsu A, Nakahara K, Chida K, Yamanouchi H, Murayama S, Tanaka N. Aortic pulse wave velocity and the degree of atherosclerosis in the elderly: a pathological study based on 304 autopsy cases. Atherosclerosis. 2005 Apr;179(2):345-51. doi: 10.1016/j.atherosclerosis.2004.09.023. Epub 2004 Dec 13.
• Background London GM, Marchais SJ, Guerin AP, Pannier B. Arterial stiffness: pathophysiology and clinical impact. Clin Exp Hypertens. 2004 Oct-Nov;26(7-8):689-99. doi: 10.1081/ceh-200031982.
• Background London GM, Marchais SJ, Guerin AP, Metivier F. Arteriosclerosis, vascular calcifications and cardiovascular disease in uremia. Curr Opin Nephrol Hypertens. 2005 Nov;14(6):525-31. doi: 10.1097/01.mnh.0000168336.67499.c0.
• Background Touyz RM. The role of angiotensin II in regulating vascular structural and functional changes in hypertension. Curr Hypertens Rep. 2003 Apr;5(2):155-64. doi: 10.1007/s11906-003-0073-2.
• Background Unger T. Pharmacological properties of angiotensin II antagonists: examining all the therapeutic implications. J Renin Angiotensin Aldosterone Syst. 2001 Sep;2 Suppl 2:S4-7. doi: 10.3317/jraas.2001.030.
• Background Matsuda H, Hayashi K, Saruta T. Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease. J Hum Hypertens. 2003 Apr;17(4):271-6. doi: 10.1038/sj.jhh.1001543.
• Background Chrysant SG. Vascular remodeling: the role of angiotensin-converting enzyme inhibitors. Am Heart J. 1998 Feb;135(2 Pt 2):S21-30. doi: 10.1053/hj.1998.v135.86971.
• Background Bertrand ME. Provision of cardiovascular protection by ACE inhibitors: a review of recent trials. Curr Med Res Opin. 2004 Oct;20(10):1559-69. doi: 10.1185/030079904X4185.
• Background Fields LE, Burt VL, Cutler JA, Hughes J, Roccella EJ, Sorlie P. The burden of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension. 2004 Oct;44(4):398-404. doi: 10.1161/01.HYP.0000142248.54761.56. Epub 2004 Aug 23.
• Background Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D'Agostino RB, Levy D. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002 Feb 27;287(8):1003-10. doi: 10.1001/jama.287.8.1003.
• Background Franklin SS, Gustin W 4th, Wong ND, Larson MG, Weber MA, Kannel WB, Levy D. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation. 1997 Jul 1;96(1):308-15. doi: 10.1161/01.cir.96.1.308.
• Background Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005 Jul 27;294(4):466-72. doi: 10.1001/jama.294.4.466.
• Background Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998 Jun 13;351(9118):1755-62. doi: 10.1016/s0140-6736(98)04311-6.
• Background Darne B, Girerd X, Safar M, Cambien F, Guize L. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality. Hypertension. 1989 Apr;13(4):392-400. doi: 10.1161/01.hyp.13.4.392.
• Background Mitchell GF, Lacourciere Y, Ouellet JP, Izzo JL Jr, Neutel J, Kerwin LJ, Block AJ, Pfeffer MA. Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Circulation. 2003 Sep 30;108(13):1592-8. doi: 10.1161/01.CIR.0000093435.04334.1F. Epub 2003 Sep 15.
• Background Hallan S, Asberg A, Lindberg M, Johnsen H. Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. Am J Kidney Dis. 2004 Jul;44(1):84-93. doi: 10.1053/j.ajkd.2004.03.027.
• Background Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun;67(6):2089-100. doi: 10.1111/j.1523-1755.2005.00365.x.
• Background McEniery CM, Yasmin, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR; ACCT Investigators. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol. 2005 Nov 1;46(9):1753-60. doi: 10.1016/j.jacc.2005.07.037. Epub 2005 Oct 10.
• Background Mitchell GF, Izzo JL Jr, Lacourciere Y, Ouellet JP, Neutel J, Qian C, Kerwin LJ, Block AJ, Pfeffer MA. Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension: results of the conduit hemodynamics of omapatrilat international research study. Circulation. 2002 Jun 25;105(25):2955-61. doi: 10.1161/01.cir.0000020500.77568.3c.
• Background Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000 Mar 13;160(5):685-93. doi: 10.1001/archinte.160.5.685.
• Background Djamali A, Sadowski E, Muehrer R, et al. Losartan Improves Renal Medullary Oxygenation and Oxidative Stress in Patients with Chronic Allograft Nephropathy. J.Am.Soc.Nephrol. 15 (Abstract Issue):SA-PO1026, 2004

Drugs

Indications