Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease.
OBJECTIVE
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.
Schieffer
Bernhard
B
Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Germany. Schieffer.Berhard@MH-Hannover.de
Bünte
Christoph
C
Witte
Jana
J
Hoeper
Kirsten
K
Böger
Rainer H
RH
Schwedhelm
Edzard
E
Drexler
Helmut
H
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000473:pathology*; D015232:Dinoprostone / Q000097:blood; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D007249:Inflammation / Q000175:diagnosis; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D000077405:Irbesartan; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001713:Biphenyl Compounds; D015850:Interleukin-6; D013777:Tetrazoles; D016753:Interleukin-10; D013928:Thromboxane A2; D004656:Enalapril; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9; D000077405:Irbesartan; D015232:Dinoprostone