Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease
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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 (PGE(2)) 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 PGE(2) 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.
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Several medications prescribed for other metabolic risk factors, including statins, nicotinic acid, fibrates, ACE inhibitors, and thiazolidinediones, have been reported to lower CRP levels.
“treat other metabolic risk factors have been reported to reduce CRP levels (eg, statins, nicotinic acid, fibrates, ACE inhibitors, thiazolidinediones). 186 -188”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [187]
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- Authors
- Schieffer, B., Bünte, C., Witte, J., Hoeper, K., Böger, R. H., Schwedhelm, E., & Drexler, H.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Schieffer, Bernhard
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 44
- Issue
- 2
- Pages
- 362-368
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2038844856
- Cited by
- 239
- References
- 45
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 10 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 9 · 2015: 6 · 2014: 7 · 2013: 11 · 2012: 16
- FWCI
- 16.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Keywords
- renin-angiotensin system blockade, angiotensin II type 1 receptor antagonism, angiotensin-converting enzyme inhibition, irbesartan, enalapril, coronary artery disease, hypertension, inflammation, platelet aggregation, thrombus formation, C-reactive protein, interleukin-6, IL-10, MMP-9, thromboxane A2, prostaglandin E2, atherosclerosis, coronary angioplasty
- MeSH terms
- Irbesartan, Angiotensin-Converting Enzyme Inhibitors, Biphenyl Compounds, C-Reactive Protein, Coronary Artery Disease, Double-Blind Method, Enalapril, Female, Humans, Hypertension, Inflammation, Male, Middle Aged, Platelet Aggregation, Tetrazoles, Thromboxane A2, Dinoprostone, Biomarkers, Interleukin-6, Interleukin-10, Matrix Metalloproteinase 9, Angiotensin II Type 1 Receptor Blockers
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