Hypertensive disease in pregnancy is a matter of concern for healthcare providers, as it may compromise the mother's and child's health and life. The findings of earlier research, drawn heavily from observational studies, suggest that hypertensive disorders may also be a risk factor for future cardiovascular disease (CVD) in the mother. A new paper provides more substantial proof that such associations are real.
Study: Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. Image Credit: ALPA PROD / Shutterstock
Hypertensive disorders of pregnancy (HDP) affect almost a tenth of all pregnancies. They are involved in nearly one in seven maternal deaths, making them the second-largest cause of global maternal morbidity. They include three conditions – gestational hypertension, pre-eclampsia/eclampsia, and chronic hypertension exacerbated by either of the above two.
The risk of future CVD in women with HDP has been reported to be 2.5 times higher, according to observational research, while prospective data indicates an increased risk of atherosclerosis in these women in the future. However, observational studies are notorious for the presence of confounding factors that may lead to invalid associations. As a result, the present study was conducted.
The current study, published in JAMA Network Open Cardiology, used Mendelian randomization (MR) to conduct a genome-wide association study (GWAS) on the relationship between these diseases to the risk of multiple CVD in the future. MR uses the genetic risk for a disease as a substitute for the actual disease itself, thus avoiding confounding factors and minimizing the risk of reverse causation since genetic factors are randomly assigned at the time of gamete formation.
The data was drawn from several European studies, and the outcomes included coronary artery disease (CAD), ischemic stroke, heart failure, and atrial fibrillation (AF).
What did the study show?
The results of the MR study showed that HDPs with a genetic constituent was linked to a 25% higher chance of developing future CAD. This included both gestational hypertension and pre-eclampsia, with a risk increase by 8% and 6%, respectively.
This effect was in part caused by the associated systolic hypertension or diabetes, which are both traditional risk factors for future CVD. When adjusted for these conditions, the direct risk due to the HDP in either condition continued to be raised by 10% and 16%, respectively.
This shows that irrespective of the presence of either systolic hypertension or gestational diabetes, there exists an independent source of CVD risk in women with HDP.
The risk of an ischemic stroke was 27% higher in women with genetically predicted HDPs. However, heart failure did not show such associations, nor did AF.
The power of MR is exploited in this study, to draw associations that could be potentially causal in nature. The study thus adds to the evidence supporting identifying these factors as increasing the risk for future CVD in mothers with HDP. The greatest strength was observed with global HDP exposure rather than for gestational hypertension or pre-eclampsia/eclampsia. This could be due to the existence of pre-existing hypertension in a subset of mothers, which could point to the presence of an underlying biological mechanism that affects the risk of CVD.
What are the implications?
The study's findings indicate that HDPs with a genetic predisposition are associated with a higher risk of CAD and ischemic stroke. However, this increase is only partly due to other cardiometabolic factors. This would suggest that HDPs should be considered risk factors for CVD.
The partial mediation of CVD risk by systolic hypertension and gestational diabetes provides targets for preventive intervention but also suggests research areas to identify the mechanism for the residual risk of CVD in HDP patients.
Endothelial dysfunction has been implicated in HDP, which might account for the residual risk of CVD via persistent endothelial damage after pregnancy that promotes atherosclerotic plaques. In addition, the endothelial injury process itself might persist after pregnancy, once activated, albeit on a subclinical level, leading to continuing endothelial damage.
Professional guidelines emphasize early screening and timely treatment of postpartum CVD or its risk factors. However, this should be supplemented by active investigations of the impact of primary prevention of CVD in women with HDP. For instance, would the risk be less if anti-hypertensive therapies were continued after childbirth?
Notably, less than 60% of women with HDP are actually followed up postpartum. Moreover, the study presents evidence that some risks are due to modifiable risk factors, namely, systolic hypertension and gestational diabetes. Therefore, these should be targeted in future studies.
This study provides genetic evidence that HDPs are associated with an increased risk of coronary artery disease and stroke, which is partly mediated by cardiometabolic factors. In light of this, HDPs should be classified as cardiovascular disease risk factors.