Association Of Total Iron Binding Capacity With Coronary Artery Disease

BackgroundCoronary artery disease (CAD) can cause great damage to human health, and is the leading cause of death and disease burden of China and most other countries. Many risk factors for CAD such as hypertension, hyperlipemia and smoking have been identified. However, data showed that these traditional risk factors only account for50%of the CAD etiology, which indicates that other factors also play an important role in the incidence of CAD. The pathological basis of coronary heart disease is atherosclerosis. When body iron was overload, free Fe2+can produce hydroxyl radical (OH·) through Fenton and Haber-Weiss reaction. A number of studies have shown that body iron might involve in the process of atherosclerosis by promoting free radicals guiding lipid peroxidation and smooth muscle cell proliferation, and have an impact on the incidence of CAD. Total iron binding capacity (TIBC) reflects the levels of transferrin and is commonly assessed in clinical settings as an indicator of iron load. Besides, unlike other iron indicators, TIBC is not affected by the inflammation. At the same time, the gender difference for TIBC is not as great as that for other iron indicators. In recent years, several studies had been conducted to examine the association between TIBC and CAD, but the results were controversial, since positive, negative or no association was found between TIBC and the CAD risk. Thus, further exploration the relationship between them has important academic value and practical significance for the prevention and control of CAD.ObjectivesTo detect the association between TIBC and CAD risk.Methods1. A hospital-based case-control study was conducted with newly-diagnosed CAD patients. Healthy controls were recruited from the healthy persons who came to the Physical Examination Center for a medical checkup. The SOD2gene C47T polymorphism was analyzed by Pyrosequencing. The concentration of serum TIBC was measured by enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate Logistic regression models were performed to estimate the effect of TIBC on CAD risk. Stratified analysis was used to explore the impact of age and sex on the relationship between TIBC and CAD. Dose-response relation was investigated between TIBC and CAD risk by dividing TIBC concentration into quartiles.2. A Meta-analysis was performed with comprehensive search for relevant articles. Fixed or random effect pooled measure was selected on the basis of the results of homogeneity test. I2was used to evaluate the Heterogeneity among studies. Meta-regression and subgroup analysis were used to explore potential sources of between-study heterogeneity (age, sex, geographic location, publication year, sample size, study design and laboratory analysis method). An analysis of influence was carried out, which describes how robust the pooled estimator is to removal of individual studies. Publication bias was estimated using Egger’s test.Main results1. The case-control study:TIBC was found associated with decreased CAD risk both in univariate (OR=0.981,95%CI=0.975,0.986) and multivariate (OR=0.979,95%CI=0.972,0.986) adjusted logistic regressions. Stratified analysis showed that gender and age have no apparent impact on the association between TIBC and CAD risk. Results of quartiles analysis(second quartile:OR=0.963,95%CI=0.488,1.901; third quartile:OR=0.197,95%CI=0.099,0.393; highest quartile:OR=0.087,95CI=0.042,0.181) suggests there is a dose-response relationship between TIBC and CAD risk.2. The Meta-analysis:results of pooled analysis on SMD showed that TIBC is a protective factor for CAD risk (SMD=-0.231,95%CI=-0.454,-0.008,I2=88.4%). Results after sensitivity analysis also suggested a significant association was found between TIBC and reduced CAD risk. Univariate meta-regression showed that no covariates had a significant impact on between-study heterogeneity except for age. Influence analysis found no individual study has excessive influence on the pooled effect. No significant publication bias was detected for Egger’s test. Results of pooled measure on OR suggested that TIBC is significantly associated with reduced CAD risk, which were consistent with those of SMD analysis.Conclusions1. TIBC might be a protective factor for CAD.2. A does-response relationship was found between TIBC and CAD risk.