Risk of Incident Atrial Fibrillation in Women With a History of Hypertensive Disorders of Pregnancy: A Population-Based Retrospective Cohort Study

Abstract

Background: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality and are associated with acute cardiac events in the peripartum period, as well as cardiovascular disease later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and its subtypes as sex-specific risk factors for AFib.

Methods: A population-based retrospective cohort study was conducted, including 771 521 nulliparous women discharged for obstetrical delivery of their first live or stillborn singleton infant between 2002 and 2017 in Ontario, Canada. Data were obtained from record-level, coded, and linked population-based administrative databases housed at ICES. Using competing risks Cox proportional hazards regression, we estimated crude and multivariable-adjusted cause-specific hazard ratios and 95% CIs for associations between history of any HDP (and its 6 subtypes), and AFib before death, as well as all-cause mortality without a previous AFib diagnosis.

Results: Approximately 8% of women were diagnosed with HDP during the 16-year exposure accrual period. The total person-time of follow-up was 7 380 304 person-years, during which there were 2483 (0.3%) incident AFib diagnoses and 2951 (0.4%) deaths. History of any HDP was associated with an increased cause-specific hazard ratios of incident AFib and death without a previous AFib diagnosis (adjusted cause-specific hazard ratios, 1.45 [95% CI, 1.28-1.64] and 1.31 [95% CI, 1.16-1.47], respectively). These associations were observed in relatively young women (median time to event, 7 years postpartum). Associations suggestive of a dose-response relationship were observed, with more severe HDP subtypes and prepregnancy chronic hypertension associated with a 1.5 to 2.2 times higher cause-specific rate of AFib, and a 1.4 to 2.1 times higher cause-specific rate of death compared with no hypertension in pregnancy.

Conclusions: Women exposed to HDP in their first delivery have a significantly increased cause-specific hazard ratios of incident AFib compared to their unexposed counterparts, with higher rates observed in subjects exposed to more severe de novo HDP diagnoses as well as chronic hypertension in pregnancy. These findings underscore the need to consider HDP history in risk calculation/stratification for arrhythmic and nonarrhythmic cardiovascular diseases, improve surveillance of traditional and female-specific cardiovascular disease risk factors, and develop targeted prevention strategies to reduce the occurrence and burden of HDP.

Keywords: atrial fibrillation; epidemiology; hypertension; preeclampsia; pregnancy; retrospective cohort.

Figure 1.

Flow diagram illustrating the selection of study subjects.

Figure 2.

Summary of the study methodology. AFib indicates atrial fibrillation; f/u, follow-up; GH, gestational hypertension; HDP, hypertensive disorders of pregnancy; HTN, hypertension; OSA, obstructive sleep apnea; and PCOS, polycystic ovarian syndrome.

Figure 3.

Proportion of study subjects (per 1000 deliveries) diagnosed with a hypertensive disorder of pregnancy during the exposure accrual period of the study, by subtype. For each hypertensive disorders of pregnancy subtype, the numerator included the total number of subjects diagnosed with that specific subtype during the study period, and the denominator included the total number of study subjects.

Figure 4.

Cause-specific cumulative incidence curves for atrial fibrillation (outcome) and all-cause mortality (competing risk) stratified by hypertensive disorder of pregnancy exposure status (first obstetrical delivery).

Figure 5.

Case-specific adjusted hazard rations for atrial fibrillation and all-cause mortality. Cause-specific multivariable adjusted hazard ratios and accompanying 95% CIs (log-scale) for atrial fibrillation (A) and all-cause mortality (B) by any hypertensive disorder of pregnancy and each subtype. Hazard ratios adjusted for maternal age at delivery, diabetes, polycystic ovary syndrome, sleep apnea, smoking, kidney disease, obesity, chronic immune-mediated conditions, and Ontario Marginalization Index material resources dimension (quintiles).