|
|
||||||||||
|
J Am Coll Cardiol, 2004; 44:362-368, doi:10.1016/j.jacc.2004.03.065 © 2004 by the American College of Cardiology Foundation |


* Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Germany
Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Germany
Manuscript received November 7, 2003; revised manuscript received February 25, 2004, accepted March 16, 2004.
* Reprint requests and correspondence: Dr. Bernhard Schieffer, Department of Cardiology and Angiology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Schieffer.Bernhard{at}MH-Hannover.de
OBJECTIVES: We evaluated whether renin-angiotensin system (RAS) blockade attenuates cardiovascular events.
BACKGROUND: Because inflammation and enhanced thrombogenesis are hallmarks of atherosclerosis, we assessed whether RAS inhibition elicits anti-inflammatory and anti-aggregatory effects.
METHODS: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), metalloprotease 9 (MMP-9), and interleukin 10 (IL-10) were determined in patients with coronary artery disease (CAD) and arterial hypertension six to eight weeks after coronary angioplasty (low-density lipoprotein serum levels <150 mg/dl). Patients were randomized double-blind to either 20 mg enalapril (ENAL, n = 27) or 300 mg irbesartan (IRB, n = 21) for 3 months. Blood samples were drawn at baseline and at three months. Thromboxane A2-induced platelet aggregation was determined turbidimetrically; urine bicyclo-prostaglandin E2 (PGE2) and inflammatory markers were measured by enzyme-linked immunosorbent assay technique.
RESULTS: Both treatment regimens enhanced serum IL-10 levels (IRB p < 0.001, ENAL p < 0.03) and reduced serum MMP-9 protein (IRB p < 0.001, ENAL p < 0.05) and MMP-9 activity (IRB p < 0.005, ENAL p < 0.05). Only IRB reduced serum IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas ENAL did not (hsCRP p < 0.02 IRB vs. ENAL, p < 0.01 IRB vs. ENAL). Platelet aggregation was only reduced by IRB (p < 0.001, ENAL p < 0.06, IRB vs. ENAL p < 0.001) while urine PGE2 levels remained unchanged.
CONCLUSIONS: Angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) blockade reduced serum MMP-9 protein/activity to a similar extent, and only AT1 blockade reduced hsCRP, IL-6, and platelet aggregation in patients with CAD. Thus, AT1-blockade appears to exert stronger systemic anti-inflammatory and anti-aggregatory effects compared with ACE inhibition.
| ||||||||||||||||||||||||||||||||||
This article has been cited by other articles:
![]() |
A Williams, S Davies, A G Stuart, D G Wilson, and A G Fraser Medical treatment of Marfan syndrome: a time for change Heart, April 1, 2008; 94(4): 414 - 421. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. B. Matchar, D. C. McCrory, L. A. Orlando, M. R. Patel, U. D. Patel, M. B. Patwardhan, B. Powers, G. P. Samsa, and R. N. Gray Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension Ann Intern Med, January 1, 2008; 148(1): 16 - 29. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Li, Y. Doerffel, B. Hocher, and T. Unger Inflammation in the genesis of hypertension and its complications the role of angiotensin II Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3107 - 3109. [Full Text] [PDF] |
||||
![]() |
F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. A. Rodriguez-Granillo, S. de Winter, N. Bruining, J. M.R. Ligthart, H. M. Garcia-Garcia, M. Valgimigli, P. J. de Feyter, and on behalf of the EUROPA/PERSPECTIVE Investigators Effect of perindopril on coronary remodelling: insights from a multicentre, randomized study Eur. Heart J., October 1, 2007; 28(19): 2326 - 2331. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Sabatine, D. A. Morrow, K. A. Jablonski, M. M. Rice, J. W. Warnica, M. J. Domanski, J. Hsia, B. J. Gersh, N. Rifai, P. M Ridker, et al. Prognostic Significance of the Centers for Disease Control/American Heart Association High-Sensitivity C-Reactive Protein Cut Points for Cardiovascular and Other Outcomes in Patients With Stable Coronary Artery Disease Circulation, March 27, 2007; 115(12): 1528 - 1536. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Ruef, M. Browatzki, C. A. Pfeiffer, J. Schmidt, and R. Kranzhofer Angiotensin II promotes the inflammatory response to CD40 ligation via TRAF-2 Vascular Medicine, February 1, 2007; 12(1): 23 - 27. [Abstract] [PDF] |
||||
![]() |
F. Persson, P. Rossing, P. Hovind, C. D.A. Stehouwer, C. Schalkwijk, L. Tarnow, and H.-H. Parving Irbesartan Treatment Reduces Biomarkers of Inflammatory Activity in Patients With Type 2 Diabetes and Microalbuminuria: An IRMA 2 Substudy Diabetes, December 1, 2006; 55(12): 3550 - 3555. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. G. de Vinuesa, M. Goicoechea, J. Kanter, M. Puerta, V. Cachofeiro, V. Lahera, F. Gomez-Campdera, and J. Luno Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease: Effects of Angiotensin II Blockade J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S206 - S212. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Luther, J. V. Gainer, L. J. Murphey, C. Yu, D. E. Vaughan, J. D. Morrow, and N. J. Brown Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor-Dependent Mechanism Hypertension, December 1, 2006; 48(6): 1050 - 1057. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M Ridker, E. Danielson, N. Rifai, R. J. Glynn, and for the Val-MARC Investigators Valsartan, Blood Pressure Reduction, and C-Reactive Protein: Primary Report of the Val-MARC Trial Hypertension, July 1, 2006; 48(1): 73 - 79. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Lucas, R. Korol, and C. J. Pepine Inflammation in Atherosclerosis: Some Thoughts About Acute Coronary Syndromes Circulation, May 2, 2006; 113(17): e728 - e732. [Full Text] [PDF] |
||||
![]() |
P. Pauletto and M. Rattazzi Inflammation and hypertension: the search for a link Nephrol. Dial. Transplant., April 1, 2006; 21(4): 850 - 853. [Full Text] [PDF] |
||||
![]() |
C. J. Boos, R. A. Anderson, and G. Y.H. Lip Is atrial fibrillation an inflammatory disorder? Eur. Heart J., January 2, 2006; 27(2): 136 - 149. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. Grundy, J. I. Cleeman, S. R. Daniels, K. A. Donato, R. H. Eckel, B. A. Franklin, D. J. Gordon, R. M. Krauss, P. J. Savage, S. C. Smith Jr, et al. Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement Circulation, October 25, 2005; 112(17): 2735 - 2752. [Full Text] [PDF] |
||||
![]() |
A. G. Herman and S. Moncada Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis Eur. Heart J., October 1, 2005; 26(19): 1945 - 1955. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-J. Li and C.-H. Fang Effects of 4 Weeks of Atorvastatin Administration on the Antiinflammatory Cytokine Interleukin-10 in Patients with Unstable Angina Clin. Chem., September 1, 2005; 51(9): 1735 - 1738. [Full Text] [PDF] |
||||
![]() |
Z. T. Bloomgarden Second World Congress on the Insulin Resistance Syndrome: Hypertension, cardiovascular disease, and treatment approaches Diabetes Care, August 1, 2005; 28(8): 2073 - 2080. [Full Text] [PDF] |
||||
![]() |
A. H. Berg and P. E. Scherer Adipose Tissue, Inflammation, and Cardiovascular Disease Circ. Res., May 13, 2005; 96(9): 939 - 949. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Morawietz Beyond Blood Pressure: Endothelial Protection Against Hypercholesterolemia by Angiotensin II Type-1 Receptor Blockade Hypertension, February 1, 2005; 45(2): 185 - 186. [Full Text] [PDF] |
||||
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |