Association Of Serum Midkine With Coronary Heart Disease And Its Risk Factors

Background:Coronary heart disease (CHD) is a common disease that threatening life and health and comes out to be one of the main causes of adults'death. It's morbility and mortality rates are increasing year by year, and the morbidity age becomes much younger gradually. The mechanism and the pathogenesis of CHD are extremely complex. More and more biomarkers have emerged as useful tools for defining myocardial damage, but helpless in judging the stricture in the vessels of CHD. Midkine (MK) is a heparin-binding growth factor, whose gene expression changes along with the individual growth. Midkine shows a high expression in the period of embryonic, which reduces gradually after birth, and is limited to special tissues in adults. Midkine is involved in diverse biological phenomena, eg, neural survival, vascularization, carcinogenesis, and tissue repair. Recent studies discovered that Midkine also participated in regulating the rennin-angiotensin system in mice. The expression of Midkine mRNA elevates in mice after myocardial ischemia. Midkine played a protective role against ischemia/reperfusion injury in the heart, most likely through a prevention of apoptotic reaction and cardiac remodeling was significantly and dose-dependently attenuated by midkine treatment. However, the relationship between animal study and clinical research in this field was still unknown. We ought to make it clear whether the serum Midkine is higher in patients with CHD and arises with severity of coronary atherosclerosis.Objective:To evaluate the clinical significance of serum Midkine in patients with CHD. To see whether serum midkine correlates with CHD, severity of coronary atherosclerosis or other established cardiovascular risk factors.Methods:The levels of serum Midkine were detected using enzyme-linked immunosorbent assay(ELISA) in 50 healthy cases and 126 patients with CHD who were diagnosed by coronary angiography(CAG). Patients with angina pectoris in the CHD were further divided into subgroups according to the number of diseased coronary branches and Gensini's score. Serum Midkine, total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C), fasting plasma glucose(FPG), creatine kinase(CK), creatine kinase MB(CK-MB), high-sensitivity C-reactive protein(hs-CRP) were evaluated. Blood pressure and body mass index (BMI) were measured. Age, sex, smoking status and prior medical histories including hypertension, diabetes mellitus of all patients were obtained. Midkine were compared statistically among the subgroups, and correlation coefficient of Midkine with other conventional risk factors of CHD was calculated. Measurement data which follows the normal distribution were described with mean±sd and T-test was used to compare the difference between two groups and the difference among three or more groups were compared with ANOVA. The Pearson method was also employed for the correlation analysis. In addition, the logistic correlation analysis was used for evaluating the relation between CHD and its risk factor. All the data were analyzed by SPSS 17.0 and P<0.05 was supposed to be statistically significant.Results:1) Level of serum Midkine in patients with CHD was significantly higher than that in controls (292.55±15.53 pg/ml vs 284.48±12.4 pg/ml , P<0.05). Levels of serum Midkine were 287.30±16.56 pg/ml in patients with AMI and 296.50±13.55 pg/ml in patients with angina pectoris. No significant difference was found in levels of serum Midkine between AMI and controls, while Midkine levels in patients with angina pectoris were significantly higher than that in healthy controls and patients with AMI (p<0.05). 2) Serum Midkine levels in double diseased coronary branches subgroup (297.92±10.02 pg/ml) and three diseased coronary branches subgroup (308.73±7.89 pg/ml) were significantly higher than that in controls (284.48±12.4 pg/ml)and single diseased coronary branch subgroup(289.03±13.56 pg/ml) (P<0.05), but no significant statistical difference was found between levels of serum Midkine of double diseased coronary branches subgroup and three diseased coronary branches subgroup (P>0.05). Serum midkine levels in 20≤Gensini's score <40 subgroup and Gensini's score≥40 subgroup were significantly higher than that in controls and Gensini's score<20 subgroup(P<0.05), but no significant statistical difference was found between levels of serum Midkineof 20≤Gensini's score <40 subgroup and Gensini's score≥40 subgroup (P>0.05). 3) The positive correlation was observed between serum midkine and BMI. There was no correlation between serum Midkine and sex, age, blood pressure, smoking status, hypertension, diabetes mellitus, TG, TC, LDL-C, HDL-C, CK or hs-CRP.Conclusion: Levels of serum midkine in patients with CHD significantly arise, mainly because of the increasing of serum midkine in patients with angina pectoris. Serum midkine has a positive correlation with the pathological severity of coronary atherosclerosis. Statistics do show a positive correlation between serum midkine and BMI, out of the established cardiovascular risk factors.