[Truncated thesis] Background & Aims- The determinants of atherosclerosis in elderly postmenopausal women are poorly understood. We do not know if the traditional coronary heart disease (CHD) risk factors remain important in this group. Despite the growing body of data relating to exogenous estrogen, we know very little about the relationship of endogenous estrogen with inflammation, CHD risk factors and subclinical atherosclerosis in elderly women. Genes that may play a role in post-menopausal cardiovascular disease (CVD)(ER-α and Apo E gene polymorphisms) have not been examined in this population for their effect on sub-clinical atherosclerosis and whether this effect is modified by the level of endogenous estrogen. We have examined the effect of established cardiovascular risk factors, endogenous estrogen and Apo E genotype on carotid artery atherosclerosis in a large group of women over the age of 70 years. In smaller sub-groups, we have examined the relationship between ER-α gene polymorphisms and atherosclerosis and the relationship between endogenous estrogen and CRP. Methods- We studied 1149 ambulatory elderly women who were recruited from the electoral role in Perth, Western Australia in 1998 and subsequently underwent carotid ultrasound assessment in 2001 according to a standardised protocol (for detection of focal plaque and measurement of intimal-medial thickness). The subjects had a mean age of 75 years (range 70 to 82 years) at baseline. We assessed the following variables in almost all subjects at baseline; time from menopause, FEI (molar ratio of plasma estradiol to sex hormone binding globulin (SHBG) x 1000), systolic and diastolic blood pressure, total cholesterol, LDL and HDL cholesterol, triglycerides, body mass index, glycated haemoglobin, homocysteine, apolipoprotein E (ApoE) genotype, history of smoking, diabetes, cardiovascular disease and medication use. Four hundred and thirty three women were analysed for estrogen receptor alpha (ERα) genotype and 100 underwent measurement of high sensitivity C-reactive protein.