While stroke is a leading cause of death and disability for both women and men, women experience a disproportionate amount of the stroke-related disease burden including a higher lifetime risk of stroke, more deaths from stroke, and worse outcomes following stroke compared with men. The objective of my thesis is to advance our understanding of the sex-specific contribution of various ischemic stroke risk factors, to examine the hormone-related biologic basis for sex differences in ischemic stroke, and to apply the new insights gained to the creation of a sex-specific stroke risk score for postmenopausal women. First, using data from the Reasons for Geographic and Racial Differences in Stroke Study, a large national prospective cohort study, I investigated whether there are sex differences in the association between two major modifiable stroke risk factors, hypertension and impaired glucose metabolism, and incident ischemic stroke. Next, using a sub cohort of the Women’s Health Initiative Study, another longitudinal cohort study, I investigated the association between low sex hormone binding globulin (SHBG) and incident ischemic stroke in a racially and ethnically diverse group of postmenopausal women, independent of other stroke risk factors. Finally, I tested the potential of SHBG and other sex-specific risk factors to improve prediction of stroke when added to previously validated risk factors. My findings demonstrated notable sex differences in stroke risk associated with modifiable risk factors, particularly hypertension and fasting blood glucose; these associations were stronger in women than men and suggest a potential need for sex-specific guidelines. Further, among postmenopausal women, there was an elevated risk of ischemic stroke associated with low SHBG, a sex hormone and steroid transporter that serves as a marker of cardiometabolic health. Addition of SHBG to traditional Framingham stroke risk factors, though, did not significantly improve overall prediction of stroke. Future work should include investigation of sex-specific genetic variability and stroke risk as well as potential guidelines that incorporate sex-specific weighting of major risk factors.
