GENETICALLY PREDICTED BLOOD PRESSURE AND RISK OF INCIDENT HYPERTENSION AT 2 TO 7 YEARS POSTPARTUM

Therapeutic Area

ASCD/CVD in Women

Background

Pregnancy represents a “stress test” that can unmask heightened risk of early onset maternal cardiovascular disease. Hypertensive disorders of pregnancy (HDP; preeclampsia/eclampsia and gestational hypertension) are associated with earlier development of chronic hypertension, which represents a key mediator for future cardiovascular disease. Whether genetic risk for high blood pressure (BP) can stratify risk of new-onset hypertension after pregnancy, beyond other factors such as HDP history and clinical characteristics, is unclear.

Methods

The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) is a prospective observational cohort that enrolled nulliparous individuals with singleton pregnancies between 2010-2013 at eight U.S. clinical centers. The present analysis included genotyped uMoM2b participants without pre-gestational chronic hypertension who completed a follow-up assessment at 2-7 years postpartum. Genetic BP risk was calculated using a genome-wide polygenic score and categorized as low (bottom quintile), intermediate (quintiles 2-4) or high (top quintile). The primary outcome was development of stage 1+ hypertension (≥130/80 mmHg or use of antihypertensive medication). Logistic regression tested the association of genetic risk with development of hypertension, adjusted for sociodemographic factors, pre-pregnancy diabetes, first-trimester BP, postpartum body mass index (BMI) and HDP history in the index pregnancy. Key secondary analyses were stratified by HDP history.

Results

Among 3,009 participants (mean age 30.8 years, 13.3% with prior HDP), 576 (19.1%) had developed hypertension by 2-7 (mean 3.2) years after delivery. Genetic risk was independently associated with incident hypertension (high vs. low genetic risk: adjusted odds ratio [aOR], 1.58 [95% CI, 1.16-2.15]; P=0.004) and higher follow-up (systolic [+2.90 mmHg; P<0.001] and diastolic BP [+2.72 mmHg; P<0.001]). In stratified analyses, high vs. low genetic risk was associated with incident hypertension in those without prior HDP (aOR 1.82 [95% CI 1.29-2.57]; P<0.001) but not in those with prior HDP (aOR 0.88 [95% CI 0.42-1.81]; P=0.75; Pinteraction = 0.09).

Conclusions

Higher BP genetic risk was independently associated with higher risk of developing incident hypertension 2-7 years after delivery in nulliparous individuals with singleton pregnancies but appeared less informative in those with prior HDP, who have higher absolute risk for progression to chronic hypertension.