NT-proBNP and Pregnancy

Increased N-terminal pro-brain natriuretic peptide (NT proBNP) released from stretched ventricular myocytes may reflect physiological adaptation of the cardiovascular system during pregnancy. Thus, levels higher than normal in early pregnancy (>125pg/ml) is a physiological phenomenon, and an inadequate NT-proBNP level signals maladaptation. An inverse relationship between this biomarker and predicts future hypertensive disorders of pregnancy and post-pregnancy chronic hypertension has been demonstrated by a recent research published in JAMA Cardiology by Hauspurg et al.

Hypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy.

The authors hypothesized that higher concentrations of NT-proBNP in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years postpartum.

A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy.

But contrary to the original hypothesis, the study found that higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy, which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use.

Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery, an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy.

Reason for the Counterintuitive Results?

"These results suggest the hypothesis that lower concentrations of NT-proBNP early in gestation may reflect impaired adaptation to pregnancy or impaired prepregnancy cardiovascular function, representing more vascular stiffness and a less robust volume expansion, which might portend risk of HDP and future hypertension," argue the authors in the discussion section.

Thus, although the NT-proBNP levels are found to be increased in a known case of pre-eclampsia, which reflects the magnitude of myocardial strain, the higher than normal levels in early pregnancy reflect a physiological adaptation to cardiovascular changes at this stage.

It can thus be inferred that a pregnant female in her first trimester with normal or below normal NT-proBNP levels is at higher risk for hypertensive disorders of pregnancy and future chronic hypertensive state post-pregnancy.

"One specific BNP gene variant, the minor C allele of the BNP genetic variant rs198389, is associated with higher levels of BNP and a lower risk of hypertension and major adverse cardiovascular events in individuals at risk of heart failure. In those without this protective genetic variant, circulating BNP levels are lower and the risk of major cardiovascular events is higher. These epigenetic changes may be at play in early pregnancy, such that a BNP deficiency state could be the primary driver of an increased risk of HDP and future hypertension, which should be a focus of future work," further note Hauspurg et al.

Overall, findings from this cohort study support the importance of early-pregnancy cardiovascular adaptation not only for healthy pregnancy outcomes but also as a marker of future cardiovascular health. Taken together, these findings suggest that early-pregnancy cardiovascular physiology, as assessed with NT-proBNP concentration, may be an important determinant of both pregnancy outcome as well as future CVD.

Source: JAMA Cardiology: doi:10.1001/jamacardio.2021.5617