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

Author(s): Ceconi C, Fox KM, Remme WJ, Simoons ML, Deckers JW, Bertrand M, Parrinello G, Kluft C, Blann A, Cokkinos D, Ferrari R

Affiliation(s): University of Ferrara, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy. claudio.ceconi@unife.it

Publication date & source: 2009-05, Atherosclerosis., 204(1):273-5. Epub 2008 Sep 10.

Publication type: Multicenter Study; Randomized Controlled Trial

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-alpha), and a biomarker of thrombosis, D-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-alpha, 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-alpha (27.60-25.20 pg/mL; P<0.05) and D-dimer (0.24-0.18 microg/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-alpha, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen).