PROJECT SUMMARY Coronary artery disease (CAD) is the leading cause of death and disability among women in the United States. It became apparent in the 1980s that the decline of cardiovascular mortality in men was not accompanied by the same rate of decline in women. The reasons for these differences may relate to worsening of the overall CAD risk profile for aging in women compared to men, which may be further potentiated by sex-based disparities in cardiovascular care: women have been both under-evaluated for CAD and under-treated for modifiable risk factors. In addition, female sex-specific conditions, such as hypertensive pregnancy disorders (HPD), together with menopause and hormone therapy, may contribute to those differences. Approximately 6%-8% of pregnancies are affected by HPD, which remains a leading cause of both maternal and fetal morbidity and mortality worldwide. HPD cover a spectrum of conditions, most notably preeclampsia, a pregnancy-specific hypertensive disorder further characterized by systemic endothelial dysfunction and proteinuria. Our overarching hypothesis is that a history of HPD in general, and preeclampsia in particular, represents a unique risk factor that is independent of traditional risk factors for future coronary artery disease (CAD) events, including myocardial infarction, coronary artery bypass grafting and percutaneous coronary intervention (Aim 1); is associated with more severe atherosclerotic disease at CAD event (Aim 2); and is related to increasing cardiovascular morbidity and death among women with CAD (Aim 3). There are no studies to date of the association between a history of HPD/preeclampsia and CAD that confirm both exposure and outcome based on accepted clinical criteria, and that stratify the outcome based on the severity of exposure while controlling for known risk factors occurring before, during, and after the affected pregnancies. This proposal will cover current gaps in knowledge by testing these associations using the unique population-based records-linkage system of the Rochester Epidemiology Project (REP). We will include all female residents of Olmsted County, Minnesota who were identified through existing cohorts and REP-based sources, and who had an incident CAD event from 2002-2017, supplemented with cohorts of incident heart failure and atrial fibrillation that will be used to ascertain subsequent cardiovascular outcomes. We will perform extensive medical record reviews to confirm the diagnoses of HPD by using validated criteria for the retrospective diagnoses of HPD. The results of the proposed research may open new venues for early detection, prevention, diagnosis, and treatment of CAD in women.
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