Key result
High-risk hypertensive pregnancy trajectories linked to ~89% higher cardiovascular mortality risk.
Why the study?
Hypertensive disorders of pregnancy are linked to maternal CVD mortality with risk varying by subtype, but the contribution of shared familial factors given this heterogeneity is unclear.
Does a history of hypertensive disorders of pregnancy increase cardiovascular disease mortality in women, and how much do shared familial factors contribute?
Cohort (n=1,106,658)
Does a history of hypertensive disorders of pregnancy increase cardiovascular disease mortality in women, and how much do shared familial factors contribute?
High-risk hypertensive disorders of pregnancy are associated with significantly elevated cardiovascular mortality driven primarily by individual-specific factors rather than shared familial genetics or early-life environment.
High-risk HDP trajectories may support enhanced CVD surveillance; extends associations via sibling analyses isolating individual over familial risks.
Hypertensive disorders of pregnancy (HDP) are associated with increased maternal cardiovascular disease (CVD) mortality, with risks varying by HDP subtypes and subsequent pregnancy outcomes. The contribution of shared familial factors given this heterogeneity is unclear. We conducted a population-based study using Norwegian registries (1967-2020) including 1 106 658 women with complete pregnancy histories, of whom 628 345 had at least one full sibling. Women with HDP were classified into low-risk (gestational hypertension or term pre-eclampsia followed by no HDPs) and high-risk (all other patterns) trajectories. CVD mortality before age 70 was assessed using population-level and sibling-based models: sibling-comparison (discordant-sisters), sibling-spillover (by sister's HDP history), and negative-control models (by sister-in-law's HDP history). CVD mortality among women with HDP varied by trajectory (population-level adjusted hazard ratios [aHR]low-risk 1.03 [95% confidence intervals, 0.89-1.20]; aHRhigh-risk 1.89 [1.74-2.06]). These differences persisted when compared to sisters without HDP (sibling-comparison aHRlow-risk 0.66 [0.44-1.01]; aHRhigh-risk 1.51 [1.16-1.97]). Women without HDP had slightly elevated CVD mortality if sisters had HDP (sibling-spillover aHRlow-risk 1.28 [1.03-1.60]; aHRhigh-risk 1.25 [1.06-1.49]), but not if sisters-in-law had HDP (negative-control aHRlow-risk 1.10 [0.85-1.40]; aHRhigh-risk 1.01 [0.83-1.22]). Individual-specific factors drive the CVD mortality heterogeneity among women with HDP. Shared familial factors modestly elevate CVD mortality in women without HDP.
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Singh et al. (2025) conducted a cohort in Hypertensive disorders of pregnancy (n=1,106,658). High-risk hypertensive disorders of pregnancy vs. Women without hypertensive disorders of pregnancy was evaluated on Cardiovascular disease mortality before age 70 (aHR 1.89, 95% CI 1.74-2.06). High-risk hypertensive disorders of pregnancy trajectories were associated with an 89% increased risk of cardiovascular disease mortality compared to women without HDP (aHR 1.89).
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