Ischemic stroke is a major cause of death and disability among postmenopausal women. One of the risk factors of ischemic stroke is diet, including dietary fat intake. It has been established that intake of trans and saturated fatty acids are positively associated with coronary heart disease, whereas monounsaturated and polyunsaturated fatty acids are inversely associated. Despite the expectation that these associations would be consistent for ischemic stroke, this has not been the case in studies using participant reported measures of fatty acid intake. Rather, studies using biomarkers of fatty acid intake, such as serum, have had more success in finding the expected associations. This dissertation attempts to explain these inconsistent results through two aims. The first aim was to estimate the correlations between individual serum fatty acids and fatty acid intakes, which may partially explain previous inconsistent results from studies using different fatty acid assessment methods. The participants were 925 women from the Women's Health Initiative Observational Study (WHI-OS) of postmenopausal US women. Serum fatty acid composition was determined from a fasting serum sample collected at enrollment. Fatty acid intakes were measured using a 122-item food frequency questionnaire also at enrollment. Individual fatty acids with the highest Spearman rank correlations between serum and dietary intake were docosapentaenoic (DHA), eicosapentaenoic (EPA), and 18:1t fatty acid. Serum saturated, monounsaturated, and n6 polyunsaturated fatty acids were not correlated with the corresponding intake measures. This work highlights the need for further research to find suitable biomarkers for intakes of individual fatty acids. The second aim was to estimate the association between individual serum fatty acids and incidence of ischemic stroke and ischemic stroke subtypes. We conducted a case-control study nested in the WHI-OS. Incident ischemic stroke cases were centrally adjudicated, classified by etiologic subtype, and matched (1:1) to controls for a total of 964 case-control pairs. Serum linelaidic, palmitic, and oleic acids were associated with higher incidence of ischemic stroke, while serum EPA, docosapentaenoic (DPA), DHA, and arachidonic acids were associated with lower incidence. These associations were generally consistent for atherothrombotic and lacunar, but not cardioembolic, stroke. This work highlights the importance of individual fatty acids in the development of particular subtypes of ischemic stroke. This dissertation brings to attention the areas for future research. First, there is a need to find suitable biomarkers for individual fatty acid intakes. Second, future studies should explore the associations between individual fatty acids and disease, not only focusing on fatty acid groups. Third, the heterogeneous etiology of ischemic stroke suggests that ischemic stroke subtypes should be examined separately. Lastly, public health initiatives to increase the intake of DHA and EPA and reduce intake of 18:1t may reduce the incidence of ischemic stroke among postmenopausal US women.Doctor of Philosoph
