Natriuretic peptides and hemodynamics in preeclampsia

doi:10.1016/j.ajog.2006.11.033

American Journal of Obstetrics and Gynecology

Volume 196, Issue 4, April 2007, Pages 328.e1-328.e7

https://doi.org/10.1016/j.ajog.2006.11.033 Get rights and content

Objective

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia.

Study Design

This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays.

Results

NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI.

Conclusion

High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Section snippets

Materials and Methods

The study cohort comprised 19 women with preeclampsia, 26 healthy women with uncomplicated pregnancies, and 15 pregnant women with chronic hypertension in the third trimester. The study was carried out at Tampere University Hospital. The procedure was explained to each subject and written consent was obtained. The Ethics Committee of Tampere University Hospital approved the study.

Preeclamptic patients had no preexisting hypertension, renal disease, heart disease, or diabetes. Preeclampsia was

Results

Concentrations of NT-proANP and NT-proBNP were significantly higher in preeclamptic women compared to chronic hypertensive and healthy subjects. In chronic hypertensive women NT-proANP and NT-proBNP were significantly higher than in normotensive pregnancies. Finding is illustrated in Figure 1. Among healthy pregnancies 23% had high NT-proANP concentration (≥ 255 pmol/L) and 31% had high NT-proBNP concentration (≥ 86 pmol/L). Meanwhile, in women with chronic hypertension 69% and 70% and in

Comment

In our study preeclamptic pregnancies had significantly higher natriuretic peptide NT-proANP and NT-proBNP concentrations compared to chronic hypertensive and normotensive pregnancies and the median values were above the level considered to be pathological in a nonpregnant population.

High NT-proANP levels are associated with left ventricular hypertrophy and diastolic or systolic dysfunction in nonpregnant populations with suspected cardiac disease.³ In preeclamptic women the heart has shown

Acknowledgments

We are grateful to Pirjo Järventausta, RN, and Satu Ruusuvuori, RN, for their valuable technical assistance. This study was supported by the Medical Research Fund of Tampere University Hospital.

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N-terminal prohormone of brain natriuretic peptide in gestational hypertension and preeclampsia – State of the art
2024, European Journal of Obstetrics and Gynecology and Reproductive Biology
N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a non-active prohormone secreted by ventricular cardiomyocytes into the circulation in response to ventricle overload, mainly due to increased blood volume. The changes in NT-proBNP levels during pregnancy have been investigated in multiple studies. In the case of hypertensive disorders of pregnancy, increased vasoconstriction leads to increased blood pressure and afterload. Together with the volume overload of pregnancy, it leads to higher NT-proBNP secretion. As hypertensive disorders of pregnancy are among the leading causes of prematurity and perinatal mortality, early prediction and diagnosis of gestational hypertension, and preeclampsia are essential for improving maternal and infant prognosis. NT-proBNP has been regarded as a potential biomarker of hypertensive disorders of pregnancy. In this review, we have thoroughly summarized the current data on the prognostic and diagnostic utility of NT-proBNP in patients with gestational hypertension and preeclampsia. NT-proBNP values may help distinguish between non-preeclamptic and preeclamptic patients, even if there are no significant differences in blood pressure. Moreover, in pregnancies complicated by preeclampsia, the value of increased NT-proBNP level is related to the stage and the severity of the disease. Further improvement of our knowledge about NT-proBNP as a diagnostic biomarker and a putative predictor of adverse cardiac events in women with hypertensive disorders of pregnancy should lead to better management of these patients.
Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana
2023, Heliyon
Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study.
This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion.
Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group.
Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.
Chronic hypertension and superimposed preeclampsia: screening and diagnosis
2022, American Journal of Obstetrics and Gynecology
Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension and is associated with increased maternal and perinatal morbidity compared with preeclampsia alone. Distinguishing superimposed preeclampsia from chronic hypertension can be challenging because, in chronic hypertension, the traditional criteria for the diagnosis of preeclampsia, hypertension, and significant proteinuria can often predate the pregnancy. Furthermore, the prevalence of superimposed preeclampsia is unlikely to be uniformly distributed across this high-risk group but is related to the severity of preexisting endothelial dysfunction. This has led to interest in identifying biomarkers that could help in screening and diagnosis of superimposed preeclampsia and in the stratification of risk in women with chronic hypertension.
Elevated levels of uric acid and suppression of other renal biomarkers, such as the renin-angiotensin aldosterone system, have been demonstrated in women with superimposed preeclampsia but perform only modestly in its prediction. In addition, central to the pathogenesis of preeclampsia is a tendency toward an antiangiogenic state thought to be triggered by an impaired placenta and, ultimately, contributing to the endothelial dysfunction pathognomonic of the disease. In the general obstetrical population, angiogenic factors, such as soluble fms-like tyrosine kinase-1 and placental growth factor, have shown promise in the prediction of preeclampsia. However, soluble fms-like tyrosine kinase-1 and placental growth factor are impaired in women with chronic hypertension irrespective of whether they develop superimposed preeclampsia. Therefore, the differences in levels are less discriminatory in the prediction of superimposed preeclampsia compared with the general obstetrical population.
Alternative biomarkers to the angiogenic and renal factors include those of endothelial dysfunction. A characteristic of both preeclampsia and chronic hypertension is an exaggerated systemic inflammatory response causing or augmenting endothelial dysfunction. Thus, proinflammatory mediators, such as tumor necrosis factor-α, interleukin-6, cell adhesion molecules, and endothelin, have been investigated for their role in the screening and diagnosis of superimposed preeclampsia in women with chronic hypertension. To date, the existing limited evidence suggests that the differences between those who develop superimposed preeclampsia and those who do not are, as with angiogenic factors, also modest and not clinically useful for the stratification of women with chronic hypertension.
Finally, pro–B-type natriuretic peptide is regarded as a sensitive marker of early cardiac dysfunction that, in women with chronic hypertension, may predate the pregnancy. Thus, it has been proposed that pro–B-type natriuretic peptide could give insight as to the ability of women with chronic hypertension to adapt to the hemodynamic requirements of pregnancy and, subsequently, their risk of developing superimposed preeclampsia. Although higher levels of pro–B-type natriuretic peptide have been demonstrated in women with superimposed preeclampsia compared with those without, current evidence suggests that pro–B-type natriuretic peptide is not a predictor for the disease.
The objectives of this review are to, first, discuss the current criteria for the diagnosis of superimposed preeclampsia and, second, to summarize the evidence for these potential biomarkers that may assist in the diagnosis of superimposed preeclampsia.
Correlation between corin, N-terminal pro-atrial natriuretic peptide and neonatal adverse prognostic in hypertensive disorders of pregnancy
2021, Pregnancy Hypertension
Atrial natriuretic peptide (ANP) regulates water-salt balance and blood pressure by promoting renal sodium and water excretion.
Our study was to investigate plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and corin in hypertensive disorders of pregnancy (HDP) patients. Furthermore, the relationship between corin/NT-proANP and neonatal adverse prognosis were evaluated.
Seventy-seven HDP patients and forty-eight normotensive women as control group were recruited. Clinical characteristic and plasma were collected. Plasma NT-proANP and corin were determined by ELISA. Gestational age, neonatal weight and APGAR scores were recorded. Statistical analysis was conducted.
NT-proANP and corin were significantly increased in HDP group compared with that of control (P < 0.05). NT-proANP and corin were significantly elevated in HDP patients who suffered from premature delivery (P < 0.05). Both NT-proANP and corin were negatively associated with delivery time, neonatal weight and APGAR scores in HDP group. Multiple regressions demonstrated that NT-proANP and corin were independent risk factor of delivery time, neonatal weight and APGAR scores.
Plasma NT-proANP and corin were significantly increased in HDP. NT-proANP and corin were associated with neonatal adverse events in HDP patients. Thus, NT-proANP and corin may become new biomarkers for evaluating severity of pregnancy and neonatal adverse events in HDP patients.
Adaptations in autonomic nervous system regulation in normal and hypertensive pregnancy
2020, Handbook of Clinical Neurology
There is an increase in basal sympathetic nerve activity (SNA) during normal pregnancy; this counteracts profound primary vasodilation. However, pregnancy also impairs baroreflex control of heart rate and SNA, contributing to increased mortality secondary to peripartum hemorrhage. Pregnancy-induced hypertensive disorders evoke even greater elevations in SNA, which likely contribute to the hypertension. Information concerning mechanisms is limited. In normal pregnancy, increased angiotensin II acts centrally to support elevated SNA. Hypothalamic sites, including the subfornical organ, paraventricular nucleus, and arcuate nucleus, are likely (but unproven) targets. Moreover, no definitive mechanisms for exaggerated sympathoexcitation in hypertensive pregnancy have been identified. In addition, normal pregnancy increases gamma aminobutyric acid inhibition of the rostral ventrolateral medulla (RVLM), a key brainstem site that transmits excitatory inputs to spinal sympathetic preganglionic neurons. Accumulated evidence supports a major role for locally increased production and actions of the neurosteroid allopregnanolone as one mechanism. A consequence is suppression of baroreflex function, but increased basal SNA indicates that excitatory influences predominate in the RVLM. However, many questions remain regarding other sites and factors that support increased SNA during normal pregnancy and, more importantly, the mechanisms underlying excessive sympathoexcitation in life-threatening hypertensive pregnancy disorders such as preeclampsia.
Circulating NT-proBNP but not soluble corin levels were associated with preeclampsia in pregnancy-associated hypertension
2019, Clinical Biochemistry
Corin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension.
We prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status.
In our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ± 3 versus 36.6 ± 3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001).
While corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.

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: Cite this article as: Tihtonen KM, Kööbi T, Vuolteenaho O, et al. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol 2007;196:328.e1-328.e7.

: The study protocol was conducted in Tampere University Hospital; the concentrations of natriuretic peptides were determined in University of Oulu.

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ResearchObstetricsNatriuretic peptides and hemodynamics in preeclampsia

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

Acknowledgments

Obstet Gynecol

Eur J Obstet Cynecol Reprod Biol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am Heart J

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

Natriuretic peptides: biochemistry, physiology, and therapeutic role in heart failure

Heart Dis

Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care

Lancet

Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy

Hypertension

Atrial natriuretic factor in pregnancy-induced hypertension and preeclampsia: increased plasma concentrations possible explaining these hypovolemic states with paradoxical hyporeninism

Am J Hypertension

Changes in concentration of human atrial natriuretic peptide in normal pregnancy and toxaemia

J Endocrinol

Research
Obstetrics
Natriuretic peptides and hemodynamics in preeclampsia