Key result
Family history of adverse pregnancy outcomes linked to ~39% higher MACE risk in unaffected sisters.
Why the study?
Does familial predisposition to adverse pregnancy outcomes increase the risk of major adverse cardiac events in women?
Cohort (n=1,218,505)
Does familial predisposition to adverse pregnancy outcomes increase the risk of major adverse cardiac events in women?
Sisters of women with adverse pregnancy outcomes have an increased risk of cardiovascular disease, highlighting a shared familial susceptibility that may warrant targeted preventive measures.
BACKGROUND AND AIMS: Adverse pregnancy outcomes (APOs) are recognized as significant female-specific risk factors for cardiovascular disease (CVD). A potential shared familial susceptibility between APOs and CVD has been proposed, but not thoroughly explored. This study employs a quasi-experimental family comparison design to investigate shared familial predisposition between APOs and CVD, by assessing risk of CVD in APO-exposed women and their APO-free sisters. METHODS: Nationwide population-based cohort study encompassing primiparous women, without prior CVD, with registered singleton births in the Swedish Medical Birth Register between 1992 and 2019, grouped into: women with ≥1 APO (165 628), APO-free sisters (60 769), and unrelated APO-free comparator women (992 108). All study participants were followed longitudinally, through linkage with national health registers, from delivery until 2021, for primary endpoint major adverse cardiac events, and its individual components: ischaemic heart disease, heart failure, and cerebrovascular events. RESULTS: Over a median follow-up of 14 years, APO-exposed women exhibited increased rates of CVDs compared with APO-free comparators. Adverse pregnancy outcome-free sisters exhibited elevated adjusted hazard ratios (aHRs) of major adverse cardiac event {aHR 1.39 [95% confidence interval (CI) 1.13-1.71]}, heart failure [aHR 1.65 (95% CI 1.14-2.39)], and cerebrovascular events [aHR 1.37 (1.04-1.72)] compared with the APO-free comparators, while no significant increase in ischaemic heart disease was observed. Within-family analysis revealed lower CVD rates in APO-free sisters compared with their APO-exposed counterparts, except for no significant difference in cerebrovascular events. CONCLUSIONS: Sisters of women with APOs face a moderately increased risk of CVD, suggesting a genetic and/or environmental influence on the association between APOs and CVDs. These findings underscore the need for evaluating the effectiveness of targeted preventive measures in women with APOs and their sisters.
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Mantel et al. (2024) conducted a cohort in Cardiovascular disease risk (n=1,218,505). Familial predisposition to adverse pregnancy outcomes (APO-free sisters) vs. Unrelated APO-free comparator women was evaluated on Major adverse cardiac events (aHR 1.39, 95% CI 1.13-1.71). APO-free sisters of women with adverse pregnancy outcomes had a higher risk of major adverse cardiac events compared with unrelated APO-free women (aHR 1.39; 95% CI 1.13-1.71).
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