Effect of angiotensin-converting enzyme inhibition on C-reactive protein levels: the ramipril C-reactive pRotein randomized evaluation (4R) trial results.
BACKGROUND
Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk and may represent a target for treating and/or monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme inhibitors on CRP levels has not been adequately studied.


METHODS
A total of 264 men and women, with CRP levels of 2 mg/L or greater and no history of cardiovascular disease, were enrolled in a 12-week randomized, double-blind, placebo-controlled study. Participants were randomly assigned to receive 10 mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome measure was the change in CRP levels from baseline to 12 weeks in the ramipril- versus placebo treated patients.


RESULTS
The mean (+/- SD) age was 53+/-9 years (60% men). Baseline demographics were similar between the volunteers allocated to receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84 mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP values over 12 weeks was --13.2% (95% CI --22.3% to --3.2% ) in the placebo group compared with --21.1% (95% CI --29.9% to --11.2%) in the ramipril group (P nonsignificant), indicating no significant reduction in the primary end point of the trial.


CONCLUSIONS
A 12-week ramipril treatment protocol for healthy middle-aged volunteers did not lower CRP levels compared with placebo. However, because of the inherent variability of CRP levels, a much larger study is required to exclude a small treatment effect.
Verma
Subodh
S
Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto.
Lonn
Eva M
EM
Nanji
Alykhan
A
Browne
Kevin
K
Ward
Richard
R
Robertson
Annette
A
Conradson
Heather
H
Hildebrand
Kathy
K
Brant
Rollin
R
Anderson
Todd J
TJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000187:drug effects*; D016001:Confidence Intervals; D003324:Coronary Artery Disease / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002097:C-Reactive Protein; D017257:Ramipril