Assessing the Risk of Atrial Fibrillation in Women with a History of Hypertensive Disorders of Pregnancy

Abstract

Cardiovascular disease (CVD) is the leading global cause of death and disability in women. Hypertension is an especially important risk factor for cardiovascular-related morbidity and mortality in women, who have additional sex-specific risk for CVD associated with hypertensive disorders of pregnancy (HDP). Despite robust evidence of a pathophysiologic relationship between chronic hypertension (HTN) and atrial fibrillation (AFib)– the most common sustained arrhythmia– there is limited and mixed evidence about the relationship between HDP and incident AFib. The primary aim of this thesis was to advance our understanding of the relationship between exposure to HDP in a first singleton delivery and incident AFib using population-based, linked, administrative data sources. However, several conceptual/methodological factors required consideration prior to undertaking this work, which were additionally addressed in three preliminary studies: a methodological guidance article, a systematic review of administrative case-finding definitions for HDP, and a population-based descriptive study of HDP prevalence in Ontario that tested/compared estimates generated using three different case-identification strategies. Most validated case-finding definitions identify HDP from administrative databases with high specificity (≥98%); however, their median sensitivity varies widely (3%-91%). Gestational hypertension was the most prevalent HDP subtype in primiparous Ontario women who delivered a live/stillborn singleton infant between 2002-2017 (~5%). However, the prevalence of any HDP is likely underestimated when these conditions are identified only using information from obstetrical discharge abstracts. Finally, people with a history of gestational hypertension, preeclampsia, or HTN in pregnancy in their first singleton delivery have a 1.5-2.2 times increased cause-specific hazard of incident AFib compared to their unexposed counterparts. Additional studies that account for the time-varying nature of HDP and relevant confounders are needed to further elucidate these associations. HDP can serve as an important warning sign for future CVD– including AFib– even before traditional risk factors become clinically apparent. Thesis findings highlight the critical need for (a) improved population-based surveillance of traditional and female-specific risk factors for CVD, (b) prevention strategies designed to reduce both the occurrence and severity of HDP, and (c) the consideration of reproductive and gynecologic history in CVD risk calculation and stratification– especially in younger women.