Abstract Body: Introduction:
Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal/perinatal mortality. In recent work, a genetic risk score improved prediction of HDPs beyond standard clinical risk factors, but the extent to which cardiovascular health (CVH) modifies HDP genetic risk is unknown.
Hypothesis:
First-trimester CVH can offset genetic risk for HDPs.
Methods:
We examined genotyped participants of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (nuMoM2b). Individual HDP genetic risk was calculated using a validated polygenic score. A composite first-trimester CVH score was adapted from the Life’s Essential 8 model; cholesterol was incorporated in a subset (47%) with available first-trimester values. Genetic risk and CVH were each grouped as low (bottom quintile), intermediate (Q2-4), and high (top quintile). Logistic regression tested the joint association of CVH and genetic risk with HDP, adjusted for age and sociodemographic covariates.
Results:
Among 5,446 participants (mean age 27.5 years), 1,339 (24.6%) developed HDP (344 [6.3%] preeclampsia, 995 [18.3%] gestational hypertension [GH]). Higher genetic risk and lower CVH were additively associated with risk of HDP (Figure 1A-B) with no significant interaction (P[interaction] >0.05). HDP incidence ranged from 11% (low genetic risk, favorable CVH) to 37% (high genetic risk, unfavorable CVH) (Figure 1C). Favorable vs. unfavorable CVH was associated with 35-62% lower risk of HDPs across genetic risk groups. Findings were broadly consistent when examining preeclampsia and GH separately and when incorporating cholesterol (i.e., using a complete Life’s Essential 8 score). Among CVH components, nonideal BMI, blood pressure, and diet conferred highest population attributable HDP risk (25%, 14%, and 12%, respectively).
Conclusion:
Higher genetic risk and lower first trimester CVH were additively associated with risk of developing HDP. Favorable CVH in early pregnancy may partially offset a higher genetic risk for HDP.