| Objectives: Serum bilirubin was used as a nontraditional risk factors for coronary artery disease(CAD),there are growing epidemiological evidences that lower serum bilirubin levels associated with increased risk of developing CAD. The conclusion which about serum bilirubin remains controversial, and the study of serum bilirubin and prognosis of CAD without report. Heme oxygenase-1(HO-1) is a rate-limiting enzyme which plays an important regulatory role in the synthesis and catabolism of bilirubin. Although lots of researches on the relation between HO-1 and CAD, the results are not conclusive. The aim of this study was to investigate the association of serum bilirubin with the prognosis of CAD. And a meta-analysis was performed to assess the association of the HO-1 gene polymorphism with CAD risk. Methods : A total of 450 patients receiving PCI and stent implantation for CAD from Jan. 2012 to May. 2013 in First Affiliated Hospital of Xinjiang Medical University with clinical follow-up. To explore the relationship of CAD and fasting serum bilirubin(FSB), biochemical laboratory data and traditional risk factors of CAD. Studies on the CAD and restenosis(RS) after coronary stenting in relation to HO-1 gene polymorphisms were searched in the PubMed/MEDLINE, Web of Science, EMBASE, CNKI database. The statistical tests were performed using Stata12.0. Results: The 432 patients with CAD who were receiving PCI and stent implantation were enrolled for our study and all patients were median followed up for 2.17±0.67 years(range 15–41 months) when termination of follow-up time was in April 2015. All the patients were divided into three groups based on their fasting serum bilirubin(FSB) mean level: high FSB group(High group; serum bilirubin ≥12.00 μmol/L; n=152), intermediate FSB group(intermediate group; 8.54< serum bilirubin <11.99 μmol/L; n=134), and low FSB group(Low group; serum bilirubin≤8.53 μmol/L; n=146). During the follow-up period of up to 3.4 years, major adverse cardiac events(MACE) occurred in 27.31 % of patients(18 cardiac deaths, 25 myocardial infarction, 29 ischemia-driven target-vessel revascularization, 46 rehospitalization due to unstable angina pectoris or heart failure). The coronary severity scores and the number of coronary artery stenosis statistically significant difference among the three groups(P=0.034 and P=0.023). Multivariate Cox regression analysis showed that decreased FSB was an predictor of MACE in CAD patients(RR=0.858, 95%CI 0.813-0.906, P=0.001). Kaplan–Meier survival analysis suggested that patients with low FSB tended to have a decreased MACE-free survival(log rank test, χ2=34.65, P=0.001). Nineteen studies, involving 9,586 patients with CAD and 11,278 controls were included in the meta-analysis. Through the heterogeneity test and sensitivity analysis of the data, a rigorous and stable relationship was found between the HO-1(GT)n repeat length polymorphism with CAD and RS risk. we also find a significant association of HO-1T(-413)A single-nucleotide polymorphism with CAD risk. Conclusion: Baseline levels of FSB is associated with the severity of CAD and can predict cardiovascular events, independent of other prognostic markers in CAD patients. Our study indicated that both HO-1(GT)n repeat length polymorphism and HO-1T(-413)A single-nucleotide polymorphism are associated with decreased risk of CAD.(GT)n repeats polymorphism but not T(-413) was associated with RS after PCI. |
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