Key result
Genetic liability to pre-eclampsia and gestational hypertension is linked to ~20% higher CVD risk.
Why the study?
Observational studies show hypertensive disorders of pregnancy are related to adverse maternal cardiovascular risk profiles later in life, but causal genetic associations are unclear.
Is genetic liability to hypertensive disorders of pregnancy associated with increased cardiovascular disease risk?
Observational (n=221,155)
Is genetic liability to hypertensive disorders of pregnancy associated with increased cardiovascular disease risk?
Odds Ratio: 1.2 (95% CI 1.02–1.41)
Genetic liability to hypertensive disorders of pregnancy is causally related to higher cardiovascular disease risk, suggesting shared biological mechanisms rather than just the pregnancy phenotype itself.
May support closer CVD monitoring after hypertensive pregnancy disorders; leaves open causality and clinical actionability.
OBJECTIVE: Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events. METHODS: We obtained genetic associations with HDPs from a genome-wide association study and used individual participant data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype. RESULTS: Our primary analysis included 221 155 ever pregnant women (mean age 56.8 (SD 7.9) years) with available genetic data. ORs for CVD were 1.20 (1.02 to 1.41) and 1.24 (1.12 to 1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings with those of nulligravidae and men. CONCLUSIONS: Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.
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Tschiderer et al. (2023) conducted an observational in Hypertensive disorders of pregnancy and cardiovascular disease risk (n=221,155). Genetic liability to pre-eclampsia/eclampsia and gestational hypertension was evaluated on CVD events (defined as myocardial infarction or stroke) (OR 1.20, 95% CI 1.02 to 1.41). Genetic liability to pre-eclampsia/eclampsia and gestational hypertension was associated with increased risk of cardiovascular disease (OR 1.20; 95% CI 1.02-1.41 and OR 1.24; 95% CI 1.12-1.38).
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