A Mendelian randomisation study suggests how pregnancy hypertensive disorders increase the longer term risk of cardiovascular diseases
In women who develop pregnancy hypertensive disorders such as preeclampsia or gestational hypertension, there is an increased future risk of cardiovascular disease according to the findings of a Mendelian randomisation study by UK and Dutch researchers.
Hypertensive disorders during pregnancy affect 8% to 10% of all pregnant women and can lead to serious complications including mortality. In fact, one systematic analysis revealed how 14% of maternal deaths were due to hypertensive disorders. Moreover, observational evidence suggests that having a pregnancy-related hypertensive disorder increases the risk of cardiovascular events in later life. Despite this finding, observational data cannot be used to determine a causal relationship due to potential confounding. One study design that can determine whether such a relationship is causal is Mendelian randomisation (MR). This approach uses the genetic risk of disease as a proxy for the disease itself and can be used to mitigate the effect of confounding, as the MR estimate can be used to interpret the effect of the exposure, in this case pregnancy-related hypertensive diseases, on the outcome of interest (cardiovascular disease).
In the current study, researchers used estimates of genetic association obtained from genome-wide association data, to examine the association between gestational hypertension and preeclampsia and the risk of subsequently developing coronary artery disease, ischaemic stroke, heart failure and atrial fibrillation. The team also employed mediation analysis based on multivariable MR, to consider the impact of potential mediators e.g., body mass index, systolic blood pressure etc, on any identified associations.
Pregnancy hypertensive disorders and future cardiovascular risk
For any genetically predicted hypertensive disorder, there was an elevated risk of developing coronary artery disease (Odds ratio, OR = 1.24, 95% CI 1.08 – 1.43, p = 0.02). The risk was also elevated when considering gestational hypertension (OR = 1.08, p = 0.04), preeclampsia or eclampsia (OR = 1.06, p = 0.03) and ischaemic stroke (OR = 1.27, P < 0.001). However, the risks were non-significant for both gestational hypertension and preeclampsia and there were also non-significant for both heart failure and atrial fibrillation.
In the mediation analysis, there was a partial attenuation of the overall risk for CAD after adjusting for systolic blood pressure (adjusted OR = 1.10 vs 1.24) and the presence of type 2 diabetes (adjusted OR = 1.16 vs 1.24).
The authors concluded that given their findings, the presence of pregnancy-related hypertensive disorders should be considered as risk factors for cardiovascular disease.
Rayes B et al. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. JAMA Netw Open. 2023