Abstract 14112: Reproductive Risk Factors and Pulmonary Arterial Hypertension in Women

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease that affects women more often than men. The female predominance has increased over time; recent U.S. cohorts demonstrate a female:male ratio of nearly 4:1. The role of women-specific risk, such as reproductive exposures, is poorly understood in the pathophysiology of PAH. Hypothesis/Goals: We hypothesize that reproductive exposures influence the development and/or severity of PAH in women. We sought to investigate the role of reproductive factors and contribution of exogenous estrogen exposures to PAH onset and severity. Methods: Using reproductive history/exposure questionnaires from 390 women with PAH, enrolled in both the PAH Biobank and United States Pulmonary Hypertension Scientific Registry, we conducted linear regression analyses to assess the association between individual disease severity variables, as well as REVEAL Lite 2.0 scores, and patient reported reproductive variables as the predictors (Table 1). We adjusted for potential confounders including age, race, BMI, and PAH sub-group (idiopathic, heritable, or associated). Results: We found that younger menopause age, less than or equal to 40 years old, associates with a lower cardiac index (CI) at diagnosis [β -0.57, p 0.02]. The association persisted when controlling for use of hormone replacement therapy (HRT). There was a trend toward lower CI in those with menopause age of 41 to 50 years old, but not statistically significant [p 0.10]. Ever use of HRT was associated with a higher pulmonary vascular resistance [β 1.6, p 0.05] and lower CI [β -0.28, p 0.01] at diagnosis. Conclusion: Premature menopause (age less than 40 years) and ever use of HRT associate with worse hemodynamics at diagnosis in women with PAH, including lower cardiac index. Further investigations into reproductive exposures may offer an opportunity for more comprehensive risk factor screening and modification by physicians treating PAH patients.