Placental angiogenic factors: A predictor of preeclampsia risk in Asian women?

Having high blood pressure (BP) during early pregnancy was associated with a greater risk of preeclampsia, likely mediated by changes in the placenta-originated angiogenic factor sFlt-1*, according to the NORA** study.

“Our findings suggest that the imbalanced angiogenic factors levels throughout gestation might play a crucial role in developing preeclampsia in women with preexisting elevated BP,” said the researchers led by Dr Zhang Jun from KK Women’s and Children’s Hospital, Singapore.  

“Our study also supports that preconception or early pregnancy high BP, defined as SBP ≥130 mm Hg or DBP ≥80 mm Hg according to 2017 ACC/AHA guideline, should cause clinical awareness both during pregnancy and in their later life,” they urged.

The prospective NORA cohort included 923 Asian women with singleton pregnancy of <14 weeks gestation who were categorized into three groups based on their BP during early pregnancy: normal (<120/<80 mm Hg), elevated (120–129/<80 mm Hg), and hypertension (≥130/≥80 mm Hg). Their blood was sampled at four time points: 11–14, 18–22, 28–32, and 34 weeks onwards for testing of serum sFlt-1 and PlGF*** levels. [BMJ Open 2019;9:e032237]

Women with higher readings of BP or mean arterial pressure (MAP) in early pregnancy had a significantly increased risk of preeclampsia. Overall, the risk of preeclampsia rose by 2.5 times with every 10 mm Hg increase in systolic BP, by 4.3 times with every 10 mm Hg increase in diastolic BP, and by 4.1 times with every 10 mm Hg increase in MAP (p<0.01).

When preeclampsia was stratified by term and preterm, every 10 mm Hg increase in diastolic BP (adjusted odds ratio [OR], 6.0) or MAP (OR, 5.6) was significantly associated with a greater risk of preterm preeclampsia (p<0.01 for both). For term preeclampsia, both systolic (OR, 3.2) and diastolic BP (OR, 3.1) appeared predictive (p<0.01 for both).    

Also, higher diastolic BP and mean arterial pressure (MAP) in early pregnancy were both significantly associated with higher sFlt-1 values throughout pregnancy while systolic BP was associated with lower P1GF values from the second trimester onwards.

“Women with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia,” noted Zhang and co-authors.

The researchers found that both sFlt-1 levels and sFlt-1/PlGF ratios were consistently higher in hypertensive than normotensive women throughout pregnancy. Among hypertensive women, sFlt-1 increased dramatically in the third trimester such that the difference vs that in normotensive women became significant from 28 weeks of gestation onwards (p≤0.001).

In contrast, there were no significant differences in the levels of PlGF between the two groups throughout pregnancy.

The ratio of sFlt-1/PlGF was, in keeping with the data for sFlt-1 and PlGF. significantly higher in the hypertensive vs normotensive women throughout pregnancy.  

“Our results showed that hypertensive women in early pregnancy might have an imbalanced angiogenic factors levels and such imbalanced angiogenic environment tended to continue during pregnancy, which might be associated with the increased risks of preeclampsia,” Zhang and co-authors suggested.

“[However,] given that most of our participants were low-risk pregnant women, our results may not be applicable to high-risk women,” they said.