Hypertensive disorders of pregnancy and risk of cardiovascular disease: A Mendelian Randomisation study in the UK Biobank

Background 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 of women and men from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). The rationale for including men and nulligravidae was to study genetic liability to HDPs and CVD risk without experiencing the underlying phenotype. We applied Mendelian Randomisation analysis using inverse variance weighted regression in our primary analysis. Results We included 264,160 women (mean age 56.4 [SD 8.0]) and 223,043 men (mean age 56.7 [8.2]) with available genetic data. Genetically proxied pre-eclampsia/eclampsia was related to higher risk of CVD with odds ratios of 1.20 (1.01, 1.43) and 1.29 (1.08, 1.53) in women and men, respectively. For genetically proxied gestational hypertension, odds ratios for CVD were 1.22 (1.10, 1.36) and 1.28 (1.16, 1.42) in women and men, respectively. Furthermore, genetically proxied HDPs were associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis in both women and men. Conclusions Genetic liability to HDPs including pre-eclampsia/eclampsia and gestational hypertension is associated with higher CVD risk, implying biological mechanisms relating to these disorders are causally related to CVD risk in both women and men.