Effects of Surgical Removal of Uterine Fibroids on Atherosclerotic Cardiovascular Disease - PROJECT SUMMARY Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among females in the US, although nearly 80% of events are preventable. Identifying reproductive aged females at high-risk of ASCVD whom early prevention may benefit is crucial to reduce the national burden of disease. Uterine fibroids have been linked to an increased risk of ASCVD due to systemic inflammation and plaque formation. However, whether treatment for uterine fibroids impacts said risk has yet to be studied using rigorous epidemiologic methods, including the use of large, real-world datasets with long-term follow-up and causal inference methods. Concerningly, the most common surgical treatments for uterine fibroids, specifically hysterectomy and myomectomy, may affect risk of ASCVD. Undergoing a hysterectomy during reproductive-aged years may lead to early onset of menopause and increased risk of ASCVD due to the early cessation of estrogen's ASCVD protection, yet this has not been examined explicitly among a cohort of pre-menopausal females with uterine fibroids. No data exists on the long-term cardiovascular effects of myomectomy. The goal of this proposal is to apply methodologically rigorous designs and leverage large-scale administrative claims to address knowledge gaps regarding real-world ASCVD events associated with uterine fibroids and respective surgical management. In Aim 1, we will estimate the effect of surgical management for uterine fibroids on risk of ASCVD using a novel sequential target trial emulation approach. Target trial emulation avoids biases that are common flaws in observational studies by articulating the causal question of interest in the form of a hypothetical randomized trial and explicitly emulating each component of such trial using observational data. Given the methodological challenge that few individuals will undergo surgical management during a prespecified eligibility period, we will emulate a series of trials with short enrollment periods applying g-methods used to address changing surgical strategies over time. Overall, the proposed research will contribute to efforts in improving long-term health among females and promoting gynecological health for lifelong wellness. It will also provide crucial support in enabling an exceptional research trainee to prepare for a career as an academic investigator focusing on applying causal inference methods to reproductive and cardiovascular epidemiology.
