Early Cardiovascular Health May Offset Genetic Risk for Hypertensive Disorders in Pregnancy: Study

A new study published in the Journal of the American College of Cardiology showed that genetic risk and better cardiovascular health (CVH) in the first trimester were independently and additively linked to a reduced risk of hypertensive disorders of pregnancy (HDP) in first-time mothers. Further favorable early pregnancy CVH may help counterbalance high genetic risk.

Preeclampsia/eclampsia and prenatal hypertension are two examples of HDPs, which are linked to long-term maternal cardiovascular disease and are a major source of morbidity and death in both the mother and the fetus. HDPs are linked to both poor cardiovascular health (CVH) and high genetic risk. However, it is uncertain if early pregnancy CVH status alters genetic risk for HDP. Thus, to examine the independent and combined relationships between genetic risk and first-trimester CVH with the development of HDP, Vineetha Mathew and team conducted this study.

The nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) was a prospective observational cohort that recruited nulliparous people with singleton pregnancies at 8 clinical locations in the US between 2010 and 2013. This research looked at genotyped participants from this study. A validated genetic risk score for HDP was used to quantify genetic risk. A CVH score for the first trimester was derived using the American Heart Association's Life's Essential 8 model. CVH and genetic risk were classified as high (top quintile), moderate (quintile 2-4), or low (lowest quintile). The creation of HDP was the main result. 

The median first-trimester CVH score for 7,499 individuals (mean age 27.0 years) was 77.1 (Q1-Q3: 67.1-85.7). In all, 1,032 individuals (13.8%) experienced an HDP, with 487 [6.5%] experiencing preeclampsia and 545 [7.3%] experiencing gestational hypertension.

HDP was independently and additively correlated with both CVH and genetic risk. Regarding the risk of HDPs, there was no discernible interaction between genetic risk and CVH (Pinteraction > 0.05). From 4.5% (low genetic risk, high CVH) to 25.7% (high genetic risk, low CVH), the incidence of HDP varied.

Across all genetic risk strata, high CVH was linked to a 53%–74% reduced risk of HDP than low CVH. When preeclampsia/eclampsia and gestational hypertension were examined independently, the results were similar. Overall, pregnancy-related genetic risk for hypertensive disorders may be reduced by early cardiovascular health screening. High genetic risk for HDP may be reduced by favorable CVH in the early stages of pregnancy.

Reference:

Mathew, V., Khan, R. R., Jowell, A. R., Yan, Q., Pe’er, I., Truong, B., Natarajan, P., Yee, L. M., Khan, S. S., Sharma, G., Patel, A. P., Cho, S. M. J., Pabon, M. A., McNeil, R. B., Spencer, J., Silver, R. M., Levine, L. D., Grobman, W. A., Catov, J. M., … Honigberg, M. C. (2025). Genetic risk and first-trimester cardiovascular health predict hypertensive disorders of pregnancy in nulliparous women. Journal of the American College of Cardiology, 85(14), 1488–1500. https://doi.org/10.1016/j.jacc.2025.02.015