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ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis : Results from the PERTINENT study

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Author: Ceconi, C. · Fox, K.M. · Remme, W.J. · Simoons, M.L. · Deckers, J.W. · Bertrand, M. · Parrinello, G. · Kluft, C. · Blann, A. · Cokkinos, D. · Ferrari, R.
Type:article
Date:2009
Institution: TNO Kwaliteit van Leven
Source:Atherosclerosis, 1, 204, 273-275
Identifier: 241499
doi: doi:10.1016/j.atherosclerosis.2008.08.042
Keywords: Health · Biomedical Research · ACE inhibition · Coronary artery disease · Inflammation · Perindopril · Thrombosis · biological marker · C reactive protein · D dimer · dipeptidyl carboxypeptidase inhibitor · fibrinogen · perindopril · placebo · tumor necrosis factor alpha · article · atherosclerosis · clinical trial · controlled clinical trial · controlled study · coronary artery disease · drug effect · drug efficacy · drug response · endothelial dysfunction · human · inflammation · major clinical study · prediction · priority journal · prognosis · survival · thrombosis · treatment duration · treatment outcome · treatment response · Angiotensin-Converting Enzyme Inhibitors · Biological Markers · C-Reactive Protein · Cardiovascular Diseases · Coronary Artery Disease · Coronary Thrombosis · Double-Blind Method · Europe · Fibrin Fibrinogen Degradation Products · Fibrinogen · Humans · Inflammation · Inflammation Mediators · Kaplan-Meiers Estimate · Perindopril · Proportional Hazards Models · Risk Assessment · Risk Factors · Time Factors · Treatment Outcome · Tumor Necrosis Factor-alpha

Abstract

The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-α), and a biomarker of thrombosis, d-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-α, and d-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-α (27.60-25.20 pg/mL; P < 0.05) and d-dimer (0.24-0.18 μg/mL; P < 0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P = 0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (d-dimer) and the proinflammatory cytokine TNF-α, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen). © 2008.