Coronary Artery Disease Metabolic Syndrome Accompanied The Survey And Its Influence On The Prognosis Of The Adiponectin Gene Single Nucleotide Polymorphisms

Objective:The coronary artery disease (CAD) population is prone to have more abnormal metabolic risk factors clustered. We investigated the prevalence of metabolic syndrome and glycometabolic status in CAD patients diagnosed by first percutaneous coronary angiography. Our aim was to determine which definition of metabolic syndrome was applicable for the CAD population. The correlation between adiponectin and metabolic risk factors of coronary heart disease in non-diabetes male patients was studied and the prognostic value of metabolic syndrome in patients with manifest CAD was assessed.Methods:A hospital-based population of 896 patients with an average age of 60 was investigated. They were divided into CAD group (655 cases) and non-CAD group (241 cases) according to the result of coronary angiography. Data of anthropometric parameters, blood pressure, fasting blood glucose, oral glucose tolerance test (OGTT) and lipid profiles were collected. Levels of serum adiponectin in 354 subjects were determined. Metabolic syndrome was defined by criteria of National Cholesterol Education Program Adult Treatment Panelâ…¢(ATPâ…¢), new International Diabetes Federal (IDF) and Chinese Diabetes Society (CDS), respectively. Patients' glucose metabolic status was assessed with World Health Organization (WHO) diagnostic criteria of diabetes mellitus in 1999. American Heart Association's grading standards for evaluating coronary artery stenosis and Gensini score were applied to assess the degree of coronary artery lesion. Partial correlation method was used to evaluate the relation between the levels of adiponectin and the abnormal metabolic risk factors. End point events were defined as hospitalization of all kinds vascular events and death of all causes. Cox regression was used to assess the prognostic value of metabolic syndrome and its individual components to the CAD patients.Result:The prevalence of metabolic syndrome in CAD population is 36.1%, 42.6% and 49.2% according to the criteria of ATPâ…¢, IDF and CDS, respectively. The definition of CDS was more effective than those of ATPâ…¢and IDF (P=0.000), Kappa consistency test showed that positive ratio according to the criteria of CDS was moderately coherent with the definition of ATPâ…¢and IDF. (Kappa value was 0.500 and 0.519, respectively, both P were 0.033).According to the WHO criteria, 305 cases (46.6%) were diagnosed as normal glucose tolerance (NGT), 152 (23.2%) cases as impaired glucose regulation (IGR), and 198 patients (30.2%) as diabetes mellitus(DM) in the CAD group. Among them 75 cases were newly defined as type 2 diabetes. The prevalence of abnormal glycometabolism in CAD group was higher than that in non-CAD group (53.4% vs 32.8%, P=0.000). Subjects were grouped into NGT (457 cases) and IGR (184 cases) and DM (229 cases) according to the different glucose metabolic status. The locations of the coronary artery lesions were similar among the three groups. The prevalence of multiple branches involvement was 40.3% in NGT group, as 54.3% in IGR group and 60.3% in DM group (P=0.000).Gensini score in IGR and DM group was higher than that in NGT group by Kruskal-wallis test [Gensini score :IGR 18(24), DM 20 (24.5) , NGT 10 (24) , P=0.000]. Subjects were subdivided into groups by the quartile value of fasting plasma glucose, postchallenge plasma glucose. It was showed that Gensini score was increasing by the levels of the fasting plasma glucose and postchallenge plasma glucose.The concentration of serum adiponectin was determined in 354 cases. The mean adiponectin levels of CAD group were 7.9(5.7-11.6)mg/L, which were lower than that of non-CAD group[10.0(7.0-13.5)mg/L, P=0.014]. Partial correlation analysis showed that the adiponectin levels were negatively correlated with the concentration of serum triglyceride, total cholesterol, postchallenge plasma glucose levels and body mass index (BMI) and positively correlated with high-density lipoprotein cholesterol (HDL-c) after age factor was adjusted. Logistic multivariable stepwise regression analysis demonstrated that levels of adiponectin were independently associated with the presence of coronary heart disease (OR 0.533).315 CAD patients were followed up for 13.9 month in average, among whom 55 cases had end point events. Only smoking and BMI and fasting plasma glucose were independent risk factors for the prognosis of the CAD patients by the Cox regression model. The presence of metabolic syndrome according to previous three definitions did not provide extra prognostic value in CAD population.Conclusions:The prevalence of metabolic syndrome in CAD population is higher than that in general asymptomatic people. The definition of IDF is more applicable than that of ATPâ…¢for Chinese population. We can find more abnormal glucose metabolism and central obesity by the definition of IDF. Abnormal glycometabolism is common in CAD population. Both prevalence of multiple branches involvement and stenosis extent of coronary artery in subjects with abnormal glucose metabolic state were greater than that in subjects with normal glucose tolerance. The levels of fasting plasma glucose and postchallenged plasma glucose are positively correlated with the degree of the stenosis in coronary artery. Adiponectin is the protective factor for the CAD patients. Smoking, BMI and fasting blood glucose can be used to predict the recurrent cardiovascular diseases events and metabolic syndrome can not provide extra prognostic value in CAD population. Objective:Adiponectin encoded by the AMP1 gene modulates insulin sensitivity and glucose homeostasis. We assessed the association of two single nucleoride polymorphisms (SNPs) at AMP1 gene (45T/G and 276G/T) with circulating adiponectin levels and cardiovascular risk factors in Chinese population.Methods:A total of 891 subjects age from 32-80 years were investigated with 592 patients attended the Cardiovascular Department of Zhong Shan Hospital and 299 healthy volunteers from the community study. Among them 438 cases were diagnosed coronary artery disease (CAD) who underwent coronary angiography. Data of anthropometric parameters, blood pressure, fasting blood glucose, oral glucose tolerance test (OGTT), lipid profiles and serum uric acid were collected. Levels of serum adiponectin in 267 subjects were determined. We used guanidine hydrochloride method for DNA extraction. Two single nucleoride polymorphisms (45T/G and 276G/T) were genotyped with TaqMan SNP allelic discrimination. A X~2 test was used to assessed whether the genotypes were in Hardy-Weinbeg equilibrium and to determine differences in genotype frequencies between CAD case and community healthy control subjects. The relationships of the two AMP1 gene variants with coronary artery disease risk factors and levels of serum adiponectin were analysed.Results:Difference in sex, smoking were observed between case and control subjects. The value of Body mass index (BMI), waist hip ratio (WHR), serum triglycerides, serum uric acid and plasma glucose were higher in CAD patients than those of community control subjects. Total serum cholesterol (TC), LDL cholesterol (LDL-c) and HDL cholesterol (HDL-c) were lower in CAD case than thoses of healthy control. The successfully rate of SNP276 allelic discrimination was 91.6%. All genotypes in both CAD case and community control subjects were in Hardy-Weinbeg equilibrium. Significant differences were observed at position +276 with T allelic being more frequent among CAD case (P=0.024). After age, sex and BMI corrected, the control subjects carried with genotype T/T+G/T had higher levels of LDL-c and serum uric acid than those with G/G. (P=0.014 and P=0.035). The CAD case T/T+G/T carders had higher levels of TC than G/G carriers (after age, sex, BMI and glucose metabolism status corrected, P=0.042), with higher levels of fasting blood glucose (P=0.055). The glucose metabolic status was not significantly associated with the distribution of genotype among CAD case subjects. The successfully rate of SNP45 allelic discrimination was 91.6%. Case and control subjects had similar genotype distribution at position +45. The CAD patients with SNP45 G/G had higher levels TC and LDL-c than those with T/G and T/T. The concentration of serum adiponectin was determined in 267 subjects. The mean adiponectin levels of CAD case subjects were 8.0(5.9-11.3)mg/L, which were lower than that of control subjects [15.1(10.6-20.2)mg/L] (P=0.000). The two AMP1 gene variants were not significantly associated with the levels of adiponectin.Conclusions:AMP1 gene polymorphism 276G/T was related with the risk factors of coronary artery disease such as dislipidemia and serum uric acid in our CAD population. CAD patients had lower levels of serum adiponectin which was not affected with the SNP276 and SNP45.