Observational studies have long suggested that women who experience hypertensive disorders of pregnancy (HDP) face a greater risk of cardiovascular disease (CVD) later in life. A new genetic epidemiological study has explored whether this association is causal, using Mendelian randomization (MR) to investigate the genetic underpinnings of this risk. The findings suggest a genetic predisposition to HDP is associated with an increased risk for several major cardiovascular events.¹

This genetic epidemiological study employed two-sample and one-sample MR analyses to assess causality.¹ The researchers used genetic instruments from the largest genome-wide association study (GWAS) on HDP to date, which included 20,064 preeclampsia cases and 11,027 gestational hypertension cases.

Two-sample MR analyses were conducted using summary-level data from the FinnGen project and other large consortia. A complementary one-sample MR analysis was performed using individual-level data from 202,876 White British women from the UK Biobank. The primary outcomes investigated were ischaemic heart disease (IHD), myocardial infarction (MI), stroke, ischaemic stroke, atrial fibrillation (AF), and heart failure (HF).

In the two-sample MR analyses, a higher genetic predisposition to preeclampsia was associated with a greater risk of IHD (odds ratio [OR] 1.20; 95% CI 1.06–1.35), MI (OR 1.29; 95% CI 1.13–1.47), stroke (OR 1.23; 95% CI 1.12–1.35), ischaemic stroke (OR 1.21; 95% CI 1.10–1.33), AF (OR 1.13; 95% CI 1.01–1.25), and HF (OR 1.11; 95% CI 1.04–1.20).¹

Similarly, a higher genetic predisposition to gestational hypertension was associated with an increased risk of IHD (OR 1.21; 95% CI 1.10–1.33), MI (OR 1.26; 95% CI 1.16–1.36), stroke (OR 1.30; 95% CI 1.23–1.37), ischaemic stroke (OR 1.24; 95% CI 1.17–1.32), AF (OR 1.29; 95% CI 1.17–1.42), and HF (OR 1.09; 95% CI 1.03–1.15).¹ The results from the one-sample analyses were broadly consistent with these findings.

The study provides genetic evidence supporting a causal link between HDP and the subsequent development of CVD. These findings reinforce the importance of recognising a history of preeclampsia or gestational hypertension as a significant risk factor for future cardiovascular events. The authors concluded that the results highlight the need for enhanced cardiovascular surveillance in this patient population.¹

While the study establishes a causal link, the authors suggest that further interventional studies are required to determine the optimal timing and format for this heightened cardiovascular surveillance in women with a history of HDP.

This study was funded by the Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond, the Lundbeck Foundation, the Leducq Foundation, and the Research Fund at Sygeforsikringen Danmark.

References

1. Nielsen ST, Luo J, Tybjærg-Hansen A, et al. Preeclampsia, gestational hypertension, and cardiovascular disease risk: a genetic epidemiological study. Eur Heart J 2025;46(41):4316–4325. https://doi.org/10.1093/eurheartj/ehaf565

2. Inversetti A, Pivato CA, Cristodoro M, et al. Update on long-term cardiovascular risk after pre-eclampsia: a systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes 2024;10:4–13. https://doi.org/10.1093/ehjqcco/qcad065

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