Abstract TH977: Endometriosis and Early-Onset Cardiovascular Disease: Effect Modification by Systemic Inflammation and Age at Menarche

Introduction: Endometriosis, a chronic gynecological condition, has been increasingly associated with increased cardiovascular disease (CVD) risk. However, the mechanisms underlying this relationship remain poorly understood. Identifying biological factors that modify this relationship may help clarify underlying pathways and highlight women at higher cardiovascular risk. Hypothesis: We hypothesized that systemic inflammation and age at menarche will modify the association between endometriosis and early-onset CVD through shared hormonal and inflammatory pathways. Methods: We analyzed data from 5,546 women aged 20–54 years in the National Health and Nutrition Examination Survey (1999–2006). Endometriosis and early-onset cardiovascular disease (i.e., CVD before age 55) were based on self-reported physician diagnoses. Early-onset CVD included congestive heart failure, coronary heart disease, angina, myocardial infarction, or stroke. Systemic inflammation was defined using laboratory measures for serum C-reactive protein (CRP, mg/dL), and categorized as low/moderate (≤0.3 mg/dL) or elevated (>0.3 mg/dL). Age at menarche (mean 12.6 ± 0.03 years) was classified as early (≤11 years), normal (12–13 years), or late (≥14 years). Multivariable survey-weighted logistic regression were used to assess associations and effect modification by CRP and age at menarche, adjusting for age, race/ethnicity, smoking status, education, hypertension, diabetes, body mass index, and insurance status. Results: Of the 5,546 women, 379 (9.0%) reported endometriosis diagnosis, 170 (3.1%) early-onset CVD and 2665 (41.7%) had elevated CRP (≥3 mg/L). Endometriosis was associated with approximately two-fold higher odds of early-onset CVD (aOR = 2.1, 95% CI: 1.3-3.4). The association was stronger among women with elevated CRP (aOR = 2.9, 95% CI: 1.7-5.0) than among those with low/moderate CRP (aOR 1.1, 95% CI: 0.5-2.3; interaction P = 0.03). Similarly, the association between endometriosis and early-onset CVD was strongest among women with early menarche (aOR = 2.9, 95% CI: 1.2-6.8) but was not significant among those with normal (aOR = 1.8, 95% CI: 0.8-4.1) and late menarche (aOR = 1.4, 95% CI: 0.5-4.0; interaction P = 0.66). Conclusion: In this nationally representative sample of U.S. women, endometriosis was associated with higher odds of early-onset CVD, with stronger effects among women with elevated CRP and earlier menarche, underscoring their potential mechanistic role.