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Relationship Between Endogenous Androgens And Coronary Artery Disease,Plasma Level Of Pro-inflammation Cytokines

Posted on:2005-08-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:D S XiaFull Text:PDF
GTID:1104360125452443Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Background: There exists a striking gender difference in coronary artery disease. Male sex is an independent risk factor for coronary heart disease after controlling other coronary heart disease risk factors. The evidence to support the perception that the gender differences in the prevalence of coronary artery disease are due to higher androgens concentration in men is lacking. The protective effect of estrogen on development of coronary heart disease in women has been confirmed in clinical and experimental studies. However, little attention has been paid to the role of androgens in the pathogenesis of coronary heart disease in men. Inflammation plays a central pathogenic role in the initiation and progression of atherosclerosis and its clinical consequence. Pro-inflammation cytokines are mediator of cellular inflammation and promote local inflammation in the arterial wall. Plasma cytokines were viewed as predictors of coronary heart disease. The link between androgens and inflammation cytokines remain unknown. Objects: To investigate the relationship between endogenous androgens and coronary artery disease, coronary heart disease risk factors as well as plasma pro-inflammation cytokines interleukine-1B (IL-1B), interleukine-6(IL-6), tumor necrosis factor-a (TNF-a), interferon- y (IFN-r) as well as the expression of CD11b/CD18 on leukocyte in men.Methods: 104 male patients with coronary heart disease determined by angiography and 96 male control subjects without coronary heart disease were included in this study. Plasma concentration of free testosterone (FT), total testosterone (TT), dehydroepiandrosterone(DHEA), dehydroepiandrosterone sulfate ester(DHEAS), estradiol(E2) and sex hormone binding globulin(SHBG) were measures by radio-immunoassay. Serum IL-1b , IL-6, TNF- a and IFN-r were detected with enzyme linked immune absorption assay(ELISA). The expression of CD116/CD18 on leukocyte was assessed by flow cytometry. Results: Men with proven CHD had significantly lower levels of FT, TT, DHEA, DHEAS,TT/E2 and CHBG than controls (p<0.05 or 0.01), and higher levels of logarithmically transformed IL-1B(lgIL-1B), IL-6, TNF-a, IFN-r as well as the expression of CD116/CD18 on leukocyte than controls (p<0.05 or 0.01) after adjusting for age. No obvious difference in E2 was found between the two groups(p>0.05). FT, TT, DHEA, DHEAS, TT/E2 and SHBG were found to be inversely associated with coronary artery disease severity score, body mass index(BMI), waist-to-hip ratio(WHR), total cholesterol, logarithmicallytransformed triglyceride, low-density lipoprotein cholesterol, fasting plasma glucose and insulin (p<0.05 or 0.01), and positively associated with high-density lipoprotein cholesterol and insulin sensitivity index (p<0.05 or 0.01). Age was positively related to SHBG (p<0.05), and negatively related to FT, TT, DHEA, DHEAS, TT/E2 (p<0.05 or 0.01). Systolic blood pressure was inversely association with FT, TT (p<0.05). No significant correlation was found between FT, TT, DHEA, DHEAS, TT/E2 , SHBG and diastolic blood pressure, nature logarithmically transformed lipoprotein(a). FT, TT, DHEA, TT/E2, SHBG were markedly associated with 1gIL-1B, IL-6, TNF-a, IFN-r and the expression of CD116/CD18(p<0.05 or 0.01). DHEAS was negatively related to IFN-r and the expression of CD116/CD18(p< 0.01). E2 was also negatively related to 1gIL-1B, IL-6, TNF-a(p<0.01).The multivariate logistic regressional analysis result demonstrated that BMI, total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure were independently and positively related to the occurrence of CHD, and FT, insulin sensitivity index were independently and negatively associated with occurrence of CHD(all p<0.01). With stepwise multiple regression analysis, insulin sensitivity index, FT, high-density lipoprotein cholesterol showed significant independent negative association with coronary artery disease severity score(all p<0.01), and age, systolic blood pressure, total cholesterol indicated significant independent positive co...
Keywords/Search Tags:Androgens, Coronary artery disease, Risk factors, Cytokines, CD11b, CD18
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