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Am J Perinatol 2025; 42(04): 511-519
DOI: 10.1055/a-2407-1761
Original Article

Can Peripheral Arterial Tonometry and Biomarkers Help Identify Women Who Will Have Progressively Worsening Hypertensive Disorders of Pregnancy?

Caitlin M. Clifford
1   Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
,
Ashley M. Hesson
1   Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
,
Ajleeta Sangtani
1   Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
,
Santhi K. Ganesh
2   Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
3   Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
,
Elizabeth S. Langen
1   Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
› Author Affiliations Funding This work was supported by the University of Michigan 2020 Rudi Ansbacher Resident and Fellow Education and Research Award.
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Abstract

Objective This study aimed to (1) evaluate whether endothelial dysfunction, as measured by peripheral arterial tonometry (PAT) indices and biomarker (soluble fms-like tyrosine kinase-1 [sFLT], brain natriuretic peptide [BNP]) levels at 34 weeks gestation, can predict progression from nonsevere to severe hypertensive disorders of pregnancy (HDPs); and (2) develop a clinical risk model for prediction of progression from nonsevere to severe HDP.

Study Design We prospectively enrolled patients with a singleton gestation carrying a nonsevere HDP diagnosis. Forty-five participants were enrolled for PAT evaluation and serum collection between 340/7 and 366/7 weeks. PAT indices (e.g., Augmentation Index normalized to a heart rate of 75 bpm [AI75]) and biomarker concentrations were assessed at enrollment. The primary outcome was progression from a nonsevere diagnosis in the late preterm period to a diagnosis of preeclampsia with severe features or superimposed preeclampsia. Statistical analyses included two-sample t-tests, Fisher's exact tests, and multivariate modeling.

Results Thirteen subjects (30%) progressed to severe disease. No significant differences in mean PAT indices between the outcome groups were found. We found a significant difference in mean sFLT values between the two groups (p = 0.02, area under the curve [AUC] of 0.609), but not in mean BNP values. An endothelial dysfunction index (presence of fetal growth restriction, “high” AI75, and positive systolic blood pressure slope) discriminated between progression and nonprogression (p = 0.03, AUC of 0.707).

Conclusion sFLT level was a marker of progression from nonsevere to severe HDP. Further, a novel endothelial dysfunction index discriminated between progression and nonprogression to severe disease with good performance.

Key Points

  • HDPs are important causes of morbidity and mortality.

  • The sequelae of HDPs are not limited to pregnancy.

  • Developing accurate tools to predict severe HDPs is of great clinical importance.

  • Our index shows promising performance for predicting progression from nonsevere to severe HDPs.

Keywords

peripheral arterial tonometry - fms-like tyrosine kinase-1 - brain natriuretic peptide - endothelial dysfunction - hypertensive disorders of pregnancy

Data Availability

The data that support the findings of this study are available from the corresponding author, C.M.C., upon reasonable request.




Publication History

Received: 20 December 2023

Accepted: 29 August 2024

Article published online:
30 September 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 2020; 135 (06) e237-e260
    CrossrefPubMedSearch in Google Scholar
  • 2 Stevens W, Shih T, Incerti D. et al. Short-term costs of preeclampsia to the United States health care system. Am J Obstet Gynecol 2017; 217 (03) 237-248.e16
    CrossrefPubMedSearch in Google Scholar
  • 3 Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33 (03) 130-137
    CrossrefPubMedSearch in Google Scholar
  • 4 Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol 2013; 209 (06) 544.e1-544.e12
    CrossrefPubMedSearch in Google Scholar
  • 5 Rolnik DL, Wright D, Poon LC. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017; 377 (07) 613-622
    CrossrefPubMedSearch in Google Scholar
  • 6 Barton JR, O'brien JM, Bergauer NK, Jacques DL, Sibai BM. Mild gestational hypertension remote from term: progression and outcome. Am J Obstet Gynecol 2001; 184 (05) 979-983
    CrossrefPubMedSearch in Google Scholar
  • 7 Chappell LC, Brocklehurst P, Green ME. et al; PHOENIX Study Group. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet 2019; 394 (10204): 1181-1190
    CrossrefPubMedSearch in Google Scholar
  • 8 Sibai BM. Chronic hypertension in pregnancy. Obstet Gynecol 2002; 100 (02) 369-377
    PubMedSearch in Google Scholar
  • 9 Grandi SM, Filion KB, Yoon S. et al. Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications. Circulation 2019; 139 (08) 1069-1079
    CrossrefPubMedSearch in Google Scholar
  • 10 Melchiorre K, Sutherland GR, Liberati M, Thilaganathan B. Preeclampsia is associated with persistent postpartum cardiovascular impairment. Hypertension 2011; 58 (04) 709-715
    CrossrefPubMedSearch in Google Scholar
  • 11 Sciatti E, Orabona R. Assessment of arterial function in pregnancy: what about peripheral arterial tonometry?. Ultrasound Obstet Gynecol 2018; 51 (05) 701-703
    CrossrefPubMedSearch in Google Scholar
  • 12 Goor DA, Sheffy J, Schnall RP. et al. Peripheral arterial tonometry: a diagnostic method for detection of myocardial ischemia induced during mental stress tests: a pilot study. Clin Cardiol 2004; 27 (03) 137-141
    CrossrefPubMedSearch in Google Scholar
  • 13 Bonetti PO, Barsness GW, Keelan PC. et al. Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. J Am Coll Cardiol 2003; 41 (10) 1761-1768
    CrossrefPubMedSearch in Google Scholar
  • 14 Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 2003; 23 (02) 168-175
    CrossrefPubMedSearch in Google Scholar
  • 15 Lavie P, Shlitner A, Sheffy J, Schnall RP. Peripheral arterial tonometry: a novel and sensitive non-invasive monitor of brief arousals during sleep. Isr Med Assoc J 2000; 2 (03) 246-247
    PubMedSearch in Google Scholar
  • 16 Halligan SC, Murtagh B, Lennon RJ. et al. Effect of long-term hormone replacement therapy on coronary endothelial function in postmenopausal women. Mayo Clin Proc 2004; 79 (12) 1514-1520
    CrossrefPubMedSearch in Google Scholar
  • 17 Yinon D, Lowenstein L, Suraya S. et al. Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction. Eur Respir J 2006; 27 (02) 328-333
    CrossrefPubMedSearch in Google Scholar
  • 18 Mannaerts D, Faes E, Goovaerts I. et al. Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function. Am J Physiol Regul Integr Comp Physiol 2017; 313 (05) R518-R525
    CrossrefPubMedSearch in Google Scholar
  • 19 Meeme A, Buga GA, Mammen M, Namugowa A. Endothelial dysfunction and arterial stiffness in pre-eclampsia demonstrated by the EndoPAT method. Cardiovasc J S Afr 2017; 28 (01) 23-29
    CrossrefPubMedSearch in Google Scholar
  • 20 Kumer K, Premru-Sršen T, Fabjan-Vodušek V, Tul N, Fabjan T, Osredkar J. Peripheral arterial tonometry and angiogenic biomarkers in preeclampsia. Hypertens Pregnancy 2018; 37 (04) 197-203
    CrossrefPubMedSearch in Google Scholar
  • 21 Sharabi-Nov A, Kumar K, Fabjan Vodušek V. et al. Establishing a differential marker profile for pregnancy complications near delivery. Fetal Diagn Ther 2020; 47 (06) 471-484
    CrossrefPubMedSearch in Google Scholar
  • 22 Mannaerts D, Faes E, Cornette J. et al. Low-flow mediated constriction as a marker of endothelial function in healthy pregnancy and preeclampsia: a pilot study. Pregnancy Hypertens 2019; 17: 75-81
    CrossrefPubMedSearch in Google Scholar
  • 23 Carty DM, Anderson LA, Duncan CN. et al. Peripheral arterial tone: assessment of microcirculatory function in pregnancy. J Hypertens 2012; 30 (01) 117-123
    CrossrefPubMedSearch in Google Scholar
  • 24 Emeasoba EU, McLaren Jr RA, Landau R. et al. Predicting preeclampsia with noninvasive measures of endothelial dysfunction: a pilot study. AJP Rep 2020; 10 (01) e20-e25
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Agrawal S, Cerdeira AS, Redman C, Vatish M. Meta-analysis and systematic review to assess the role of soluble FMS-like tyrosine kinase-1 and placenta growth factor ratio in prediction of preeclampsia: The SaPPPhirE Study. Hypertension 2018; 71 (02) 306-316
    CrossrefPubMedSearch in Google Scholar
  • 26 Resnik JL, Hong C, Resnik R. et al. Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women. Am J Obstet Gynecol 2005; 193 (02) 450-454
    CrossrefPubMedSearch in Google Scholar
  • 27 Conti-Ramsden F, Gill C, Seed PT, Bramham K, Chappell LC, McCarthy FP. Markers of maternal cardiac dysfunction in pre-eclampsia and superimposed pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 2019; 237: 151-156
    CrossrefPubMedSearch in Google Scholar
  • 28 Rafik Hamad R, Larsson A, Pernow J, Bremme K, Eriksson MJ. Assessment of left ventricular structure and function in preeclampsia by echocardiography and cardiovascular biomarkers. J Hypertens 2009; 27 (11) 2257-2264
    CrossrefPubMedSearch in Google Scholar
  • 29 Itamar Medical. EndoPAT 2000 Device User Manual. 2019
    Search in Google Scholar
  • 30 Orabona R, Sciatti E, Vizzardi E. et al. Endothelial dysfunction and vascular stiffness in women with previous pregnancy complicated by early or late pre-eclampsia. Ultrasound Obstet Gynecol 2017; 49 (01) 116-123
    CrossrefPubMedSearch in Google Scholar
  • 31 American College of Obstetricians and Gynecologists. Fetal Growth Restriction: ACOG Practice Bulletin, Number 227. Obstet Gynecol 2021; 137 (02) e16-e28
    CrossrefPubMedSearch in Google Scholar
  • 32 Kenny LC, Black MA, Poston L. et al. Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study. Hypertension 2014; 64 (03) 644-652
    CrossrefPubMedSearch in Google Scholar
  • 33 Hauspurg A, Marsh DJ, McNeil RB. et al; NICHD nuMoM2b and NHLBI nuMoM2b Heart Health Study Networks. Association of N-terminal pro-brain natriuretic peptide concentration in early pregnancy with development of hypertensive disorders of pregnancy and future hypertension. JAMA Cardiol 2022; 7 (03) 268-276
    CrossrefPubMedSearch in Google Scholar