PROJECT SUMMARY Endometriosis burdens ~11% of women and cardiovascular disease (CVD) is the leading cause of mortality among US women. Women who have a history of endometriosis may be at increased risk of chronic diseases, including CVD due to higher levels of inflammation, greater risk of hypertension, and greater risk for hyperlipidemia. A few studies have shown higher risk of coronary heart disease and cerebrovascular disease for those with endometriosis; however, studies have been limited by short follow-up (<10 years) or small, cross-sectional design. In addition, prior studies have not incorporated information on endometriosis subtypes or reproductive history (i.e., infertility, adverse pregnancy outcomes), all of which may alter CVD risk. Thus, there are significant gaps in our knowledge regarding the complex association between endometriosis and CVD. The proposed research will leverage data from two existing cohorts—a well-phenotyped research cohort embedded within a large representative population cohort—to investigate the relationship between endometriosis and risk of clinical and subclinical CVD. Specifically, we will analyze data from the Utah Population Database (Population Cohort) and the NICHD ENDO study (Research Cohort). The Population Cohort comprises electronic health records and vital statistics of >80,000 women with endometriosis matched 1:5 by birth year and birthplace to women with no history of endometriosis and has up to 32 years of follow-up to allow for the development of clinical CVD. The Research Cohort comprises 506 women who were assessed for endometriosis between 2007 and 2009; 184 women were diagnosed with endometriosis. Participants in the NICHD ENDO study will be re-contacted and screened for CVD risk factors and subclinical CVD markers during a new clinical visit. Leveraging both the Population Cohort and the Research Cohort, we will determine whether women with a history of endometriosis have an increased risk of a composite CVD outcome, and components of composite CVD outcome, including incident cardiovascular events, chronic hypertension, metabolic syndrome, type 2 diabetes, dyslipidemia, and chronic kidney disease compared to women without a history of endometriosis (Aim 1). We will also determine if risk of composite CVD outcome and components of composite vary by endometriosis subtype (deep infiltrating, endometriomas, superficial) (Aim 2). Via our ENDO Follow-Up Study we will determine if endometriosis increases risk of subclinical CVD, measured by CVD risk scores, cardiac CT scans, and brain MRIs compared to those without endometriosis (Aim 3). Finally, we will determine if endometriosis mediates the relationship between young adult atherogenic profile and mid-life CVD (Aim 4). The proposed project provides an unprecedented opportunity to rigorously investigate endometriosis and risk for clinical and subclinical CVD, and the role that a woman’s underlying predisposition to CVD plays in the endometriosis–CVD link. Our study findings may help inform women’s professional health guidelines in the prevention, screening, early detection, and treatment of CVD risk factors among women with endometriosis.

PROJECT NARRATIVE Endometriosis is a common gynecologic condition that may increase a woman’s risk for cardiovascular disease later in life. Using data from the Utah Population Database and the NICHD ENDO study, we propose the largest and longest study on this topic to investigate the association between endometriosis and risk of clinical and subclinical cardiovascular disease, taking into account sociodemographic characteristics and reproductive history. Understanding these associations will help improve the identification of women who are at high risk for cardiovascular disease, which may allow for early interventions and ultimately reduce morbidity and mortality.