PERTINENT--perindopril-thrombosis, inflammation, endothelial dysfunction and neurohormonal activation trial: a sub-study of the EUROPA study.
BACKGROUND
Markers of thrombosis, inflammation, endothelial dysfunction and neurohumoral activation such as fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A are reported to be linked to the increase of cardiovascular risk for atherosclerosis progression and events in patients with cardiovascular diseases.


METHODS
EUROPA is a double blind, placebo-controlled trial on 12,231 patients that evaluates the effect of an angiotensin converting enzyme inhibitor--perindopril--on prevention of cardiovascular events in patients with coronary artery disease. PERTINENT is a sub-study of EUROPA that evaluates (a) in Part A (300 patients): the influence of perindopril vs. placebo on fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A. In addition, NOS expression and induction of apoptosis on human umbilical vein endothelial cells and angiotensin converting enzyme levels are also studied; (b) in Part B (about 1200 patients): the predictive role of plasma levels of C-reactive protein and von Willebrand factor on the occurrence of cardiovascular events. To this end, matched case-control analyses are planned (patients with vs. patients without events). STATUS OF PERTINENT: Blood analyses are in progress in four specialised laboratories: (a) Gaubius Laboratory, Leiden, TNO-PG, The Netherlands; (b) University Department of Medicine, Birmingham, UK; (c) University of Pavia, Italy; (d) Fondazione Salvatore Maugeri, Cardiovascular Research Centre, Gussago, Italy.


CONCLUSIONS
The PERTINENT sub-study might help elucidating the phenomena contributing to the pathophysiology of cardiovascular events in patients with coronary artery disease and the role of perindopril in such context.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005060:Europe; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood*; D020913:Perindopril / Q000627:therapeutic use*; D012307:Risk Factors; D013927:Thrombosis / Q000517:prevention & control; D014471:Umbilical Veins / Q000166:cytology
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D018377:Neurotransmitter Agents; D020913:Perindopril