Pregnancy and cardiovascular health in caring for women with systemic lupus erythematosus - Project Summary Systemic lupus erythematosus (lupus) is a chronic, multisystem, autoimmune disease that disproportionately affects women (approximately 8 to 1), and it is typically diagnosed during the reproductive years. Preeclampsia, a serious pregnancy complication characterized by high blood pressure, is 3 times more common in women with lupus compared with other women, but there has been limited research into how medical management of lupus during pregnancy could prevent preeclampsia and other hypertensive disorders of pregnancy (HDP). Hydroxychloroquine (HCQ) is a lupus maintenance drug that women are recommended to continue during pregnancy, but for women with well-controlled lupus who are not taking HCQ prior to pregnancy, recommendations are less clear. HCQ helps manage lupus symptoms during pregnancy; it may also decrease the risk of HDP although the current literature is inconsistent, likely due to small sample size in prior studies. On the other hand, women who conceive with active lupus often need to change their treatments to drugs that are considered safe during pregnancy. There is limited evidence that suggests use of high dose corticosteroids may increase the risk of preeclampsia, but less is known about other drugs, such as azathioprine, or about the effects of different treatments on HDP more broadly. Of additional concern, in the general population, history of HDP has been associated with hypertensive-related outcomes, such as kidney and cardiovascular disease, postpartum and later in life. This relationship is of particular concern for women with lupus who are already at substantially higher risk of hypertensive-related outcomes during their reproductive years compared to the general population. Pregnancy itself may even increase the risk of these outcomes among women with lupus. Thus, pregnancy history may serve as an important marker to identify women with lupus at the greatest risk of hypertensive-related outcomes. We will address current gaps in knowledge through the following aims: 1) To what degree does HCQ decrease the risk of HDP among women with well-controlled lupus before pregnancy, 2) Which approaches to medical management of lupus decrease the risk of HDP among women with active lupus before pregnancy, and 3) To what degree does pregnancy history predict hypertensive-related outcomes, including kidney and cardiovascular disease, outside of pregnancy? We will address these aims using 17 years of data from Merative™ MarketScan® Research Databases, which will include around 4,700 pregnancies to women with lupus. The data include de-identified, individual-level enrollment records and inpatient, outpatient, and drug claims data for a cohort of privately insured individuals. The proposed work is directly aligned with the goals for this request for applications. Expected outcomes from the proposed work will 1) contribute evidence directly relevant to treatment decisions for women with lupus during pregnancy, and 2) provide insights into the role pregnancy history may play in identifying women with lupus at high risk for future hypertensive-related outcomes.
