Abstract
BACKGROUND AND AIMS: Observational studies show that women with hypertensive disorders of pregnancy have greater risk of cardiovascular disease later in life. Whether these associations reflect causal pathways is uncertain. This study used genetic epidemiology to explore the causal relevance of preeclampsia and gestational hypertension on cardiovascular disease.
METHODS: Two-sample Mendelian randomization (MR) analyses were conducted using summary-level data from FinnGen and from the to date largest consortia for each outcome. One-sample MR analyses were performed using individual-level data from 202 876 White British women from the UK Biobank. Genetic instruments for preeclampsia and gestational hypertension were from the most updated genome-wide association study (n = 20 064 preeclampsia cases; n = 703 117 controls; n = 11 027 gestational hypertension cases; n = 412 788 controls).
RESULTS: In two-sample MR analyses, higher genetic predisposition to preeclampsia was associated with greater risk of ischaemic heart disease [odds ratio 1.20 (95% confidence interval 1.06-1.35)], myocardial infarction [1.29 (1.13-1.47)], stroke [1.23 (1.12-1.35)], ischaemic stroke [1.21 (1.10-1.33)], atrial fibrillation [1.13 (1.01-1.25)], and heart failure [1.11 (1.04-1.20)]. For higher genetic predisposition to gestational hypertension, corresponding odds ratios were 1.21 (1.10-1.33), 1.26 (1.16-1.36), 1.30 (1.23-1.37), 1.24 (1.17-1.32), 1.29 (1.17-1.42), and 1.09 (1.03-1.15). The MR-Egger results did not suggest pleiotropy. One-sample analyses were broadly consistent with the main findings.
CONCLUSIONS: Genetic predisposition to hypertensive disorders of pregnancy was associated with greater risk of cardiovascular disease later in life, highlighting the importance of enhanced cardiovascular surveillance in this population.