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 (CVD) later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and individual HDP subtypes as sex-specific risk factors for AFib. Methods A population-based retrospective cohort study of 771,521 nulliparous women discharged for obstetrical delivery of their first live or stillborn singleton infant between 2002-2017 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 (csHRs) and 95% confidence intervals (CIs) for associations between history of any HDP–and its six subtypes–and AFib before death, as well as all- cause mortality without a prior AFib diagnosis. Results Approximately 8% of subjects 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 2,483 (0.3%) incident AFib diagnoses and 2,951 (0.4%) deaths. History of any HDP was associated with an increased csHazard of both incident AFib and death without a prior AFib diagnosis [adjusted csHRs (95% CIs): 1.45 (1.28-1.64) and 1.31 (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 also observed, whereby both HDP severity, and presence of pre-pregnancy chronic hypertension, were associated with higher rates of both outcomes. Conclusions People exposed to HDP in their first delivery have a significantly increased csHazard 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. Given the substantial morbidity and mortality burden of AFib in women, these findings underscore the critical importance of considering history of HDP in risk calculation/stratification for both arrhythmic and non-arrhythmic CVDs; improving population-based surveillance of traditional and female-specific CVD risk factors; and developing targeted prevention strategies aimed at reducing the occurrence and burden of HDP. Clinical Perspective What is new? In this population-based retrospective cohort study of 771,521 nulliparous women, a history of hypertensive disorders of pregnancy (HDP) significantly increased the cause-specific hazard of incident atrial fibrillation (AFib) compared to women without HDP, even after adjustment for confounders, and this association was observed in relatively young women (median follow-up: 7 years postpartum). Associations suggestive of a ‘dose-response’ relationships were observed, whereby subjects with more severe de novo HDP diagnoses, as well as those with pre-pregnancy chronic hypertension, had higher cause-specific rates of AFib, with the highest rate observed in subjects exposed to chronic hypertension in pregnancy. What are the clinical implications? These findings suggest that women with a history of any HDP–especially those with pre-pregnancy chronic hypertension–may benefit from closer monitoring for the early detection of AFib. Enhanced population-based surveillance of, and targeted strategies to prevent, HDP as a female-specific cardiovascular risk factor are needed to mitigate intermediate- and long-term cardiovascular disease risk associated with these adverse pregnancy conditions.

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