Impact of C-reactive protein on in-stent restenosis: a meta-analysis

Abstract

We sought to evaluate the impact of C-reactive protein (CRP) levels on in-stent restenosis after percutaneous coronary intervention.The plasma level of CRP is considered a risk predictor for cardiovascular diseases. However, the relationship between CRP and in-stent restenosis has been a matter of controversy. Meta-analysis reduces variability and better evaluates the correlation.We performed a systemic search for literature published in March 2008 and earlier, using MEDLINE(R), the Cochrane clinical trials database, and EMBASE(R). We also scanned relevant reference lists and hand-searched all review articles or abstracts from conference reports on this topic. Of the 245 studies that we initially searched, we chose 9 prospective observational studies (1,062 patients).Overall, CRP concentration was higher in patients who experienced in-stent restenosis. The weighted mean difference in CRP levels between the patients with in-stent restenosis and those without was 1.67, and the Z-score for overall effect was 2.12 (P=0.03). Our subgroup analysis that compared patients with stable and unstable angina showed a weighted mean difference in the CRP levels of 2.22 between the patients with and without in-stent restenosis, and the Z-score for overall effect was 2.23 (P=0.03) in 5 studies of unstable-angina patients. There was no significance in 4 studies of stable-angina patients.In spite of significant heterogeneity across the studies, our meta-analysis suggests that preprocedurally elevated levels of CRP are associated with greater in-stent restenosis after stenting and that this impact appears more prominent in unstable-angina patients.

Keywords: Angina pectoris/epidemiology; C-reactive protein/analysis/metabolism; angioplasty, transluminal, percutaneous coronary; biological markers/blood; clinical trials as topic; coronary artery disease/etiology/physiopathology; coronary restenosis/etiology/pathology/prevention & control; inflammation/complications; risk factors; stents/adverse effects.

Fig. 1 Flow diagram of the trial-selection process. BMSs = bare-metal stents; CRP = C-reactive protein; DESs = drug-eluting stents; ISR = in-stent restenosis; MACE = major adverse coronary event; RCTs = randomized controlled trials

Fig. 2 Comparison of CRP levels between ISR and no-ISR groups in the 9 included studies. CI = confidence interval; ISR = in-stent restenosis; WMD = weighted mean difference

Fig. 3 Comparison of C-reactive protein levels between ISR and no-ISR groups in the 4 included stable-angina studies. CI = confidence interval; ISR = in-stent restenosis; WMD = weighted mean difference

Fig. 4 Comparison of C-reactive protein levels between ISR and no-ISR groups in the 5 included unstable-angina studies. CI = confidence interval; ISR = in-stent restenosis; WMD = weighted mean difference

Fig. 5 Funnel plot of the meta-analysis. Comparison: ISR versus no-ISR. Outcome: ISR. ISR = in-stent restenosis; SE = standard error; WMD = weighted mean difference