Pregnancy Loss and Cardiovascular Disease: A Nationwide Cohort Study

Objectives: To examine how pregnancy loss influences the risk of cardiovascular disease later in life. Design: Prospective historical cohort study. Setting: Danish nationwide health registries. Participants: All Danish women with a recorded pregnancy from 1977 to 2017. Main outcome measures: Venous thromboembolism, myocardial infarction, or ischemic stroke. Results: In this two-part study, part one evaluated the 20-year absolute risk of cardiovascular disease from age 40 among 596,699 women with a full registered reproductive history. Adjusting for calendar year, diabetes, autoimmune disease, live births, and education, the absolute risk of an outcome after 0 and ≥4 pregnancy losses, respectably was: venous thromboembolism 3.0% (95% CI 2.8 to 3.2%) and 5.0% (3.4 to 6.8%); myocardial infarction 1.5% (1.4 to 1.6%) and 2.4% (1.4 to 3.6%); ischemic stroke 2.0% (1.9 to 2.1%) and 2.6% (1.5 to 3.6%). Prior stillbirth increased the absolute risk of later venous thromboembolism by 1.1% (0.2 to 2.3%); myocardial infarction by 1.1% (0.3 to 2.0%). In study part two, we included 966,490 women from first pregnancy in a time-dependent Cox regression model. Adjusted for confounders, each additional pregnancy loss increased the hazard ratio of venous thromboembolism 1.10 (95% CI 1.07 to 1.13); myocardial infarction 1.12 (1.07 to 1.18); and ischemic stroke 1.10 (1.06 to 1.14). Stillbirth was strongly associated with myocardial infarction before age 40, adjusted hazard ratio of 4.60 (2.65 to 8.00). Conclusion: Pregnancy loss was associated with later venous thromboembolism, myocardial infarction, and ischemic stroke. The absolute and relative risk of outcomes increased in a dose-response manner with increasing numbers of prior pregnancy losses. Stillbirth was strongly associated with myocardial infarction before age 40.