Are adverse pregnancy outcomes associated with the accelerated development of cardiovascular events in parous women with systemic lupus erythematosus? A population-based study

Abstract

Background: Women between 35-44 years with systemic lupus erythematosus (SLE) have a 50-fold increase risk of cardiovascular events (CVE) despite a paucity of traditional cardiovascular risk factors. Studies to determine the cause for the high prevalence of CVE are flawed by the inclusion of older male patients who have an abundance of cardiovascular risk factors; therefore, these studies have produced conflicting results. In the general population, maternal-placental syndrome (MPS) is associated with a two-fold increase risk of myocardial infarction. A quarter of pregnancies in women with SLE are complicated by MPS and 31% will have a preterm delivery. Hypothesis: MPS and preterm deliveries are associated with accelerated CVE seen in women with SLE. Methods: Utilising linked Swedish population registries between 1973-2011, parous women with SLE were included in the analysis. Outcome of interest was CVE – defined as coronary artery disease, stroke and peripheral vascular disease or death from any those conditions. Exposures of interest were: (i) MPS which comprised hypertensive disorders of pregnancy, small-for-gestational age, placental abruption or stillbirth; (ii) preterm delivery. Hazard of developing CVE was estimated using Cox proportional hazards; survival expressed utilising Kaplan-Meier curves. Results: Over the 38-year interval 3,977 parous women with SLE were included. Those who had CVE and primary cardiovascular deaths had more SLE-related comorbidities and cardiovascular risk factors. Despite adjustment, those with MPS still had a 2-fold increase risk of primary cardiovascular death. (adjusted odds ratio (adjOR) 2.2; 95% confidence interval (CI) 1.1-4.2). MPS was associated with a 1.6- fold increase (adjusted hazards ratio (adjHR) 1.6; 95% CI 1.3-2.1) and, when MPS was combined with delivery pre-34 weeks’, the risk was two-fold increased (adjHR 2.0; 95% CI 1.4-2.8). Pre-34-week delivery was associated with a 1.8-fold increase in CVE (adjHR 1.8l; 95% CI 1.3-2.5). Median age of parous women with SLE developing CVE was only 50 (IQR 41-57) years. Both MPS and delivery pre-34 weeks were associated with accelerated development of CVE compared to the women who had uncomplicated term deliveries. Conclusion: MPS and delivery prior to 34 weeks’ were associated with an increased risk and accelerated development of CVE in parous women with SLE.