Maladie coronarienne chez la femme: Influence des hormones et du polymorphisme insertion/deletion du gene de l'enzyme de conversion de l'angiotensine

This thesis included data on different aspects of the coronary artery disease in women. Firstly, the genetic polymorphisms of angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (AT1R A1166C) were studied in a case-control study in postmenopausal women. Our data suggest an association between the ACE-DD genotype and acute coronary syndrome (ACS), particularly in hormone replacement therapy (HRT) users. The oligenic combination of ACE-DD and AGT M235T-TT genotypes was more frequent in women with ACS. Secondly, the influence of the menstrual cycle on the timing of ACS in premenopausal women was studied. Our data show that most of women presented their ACS during the menstrual phase where the 17beta-estradiol levels are lower. Also, the frequency of the ACE-DD genotype was significantly higher in women with ACS during the first six days. These data suggest that both an activated renin-angiotensin system and hormonal conditions during and immediately after the menstruation could contribute to ACS. Thirdly, an evaluation of endothelial function by brachial echocardiography (reactive hyperemia) in postmenopausal women without coronary disease was conducted. The results suggest that the ACE-DD genotype is related with lower endothelial function in comparison to ACE-II genotype. The AGT M235T and AT1R A1166C polymorphisms did not influence endothelial function. Our data suggest that HRT preserved endothelial function in ACE-DD postmenopausal women. Finally, symptomatology of women with ACS was evaluated by a structured questionnaire. More than 70% of women with ACS presented typical chest symptoms but presented frequently, both typical and atypical symptoms. Atypical chest symptoms were more frequent in premenopausal women compared to postmenopausal women using or not HRT. In conclusion, endothelial dysfunction and ACS in women in light to menstrual cycle and HRT may interact with the ACE gene.