Cardiac Biomarkers in hypertensive disorders of pregnancy

Dolina Gencheva; Fedya Nikolov; Ekaterina Uchikova; Krasimira Hristova; Rosen Mihaylov; Blagovesta Pencheva

doi:10.3889/oamjms.2021.5913

Authors

Dolina Gencheva Department of Internal Diseases, Section of Cardiology, Medical University - Plovdiv, Plovdiv, Bulgaria; Clinic of Cardiology, UMHAT “Sveti Georgi” Plovdiv, Plovdiv, Bulgaria https://orcid.org/0000-0001-7664-4329
Fedya Nikolov Department of Internal Diseases, Section of Cardiology, Medical University - Plovdiv, Plovdiv, Bulgaria; Clinic of Cardiology, UMHAT “Sveti Georgi” Plovdiv, Plovdiv, Bulgaria
Ekaterina Uchikova Department of Obstetrics and Gynaecology, Medical University-Plovdiv, Plovdiv, Bulgaria; Clinic of Obstetrics and Gynaecology, UMHAT “Sveti Georgi” Plovdiv, Plovdiv, Bulgaria
Krasimira Hristova Department of Cardiology, MHAT for women’s Health “Nadezhda”, Sofia, Bulgaria
Rosen Mihaylov Independent Medical Diagnostic Laboratory “RAMUS”, Sofia, Bulgaria; Medical College “Jordanka Filaretova”, Sofia, Bulgaria
Blagovesta Pencheva Independent Medical Diagnostic Laboratory “RAMUS”, Sofia, Bulgaria

DOI:

https://doi.org/10.3889/oamjms.2021.5913

Keywords:

Biomarkers, Preeclampsia, Gestational hypertension, Cardiovascular risk, Natriuretic peptides, Troponin, Growth/differentiation factor 15, Suppression of tumorigenicity-2, Galectin-3

Abstract

In recent years, biomarkers have taken a central place in the assessment of cardiovascular diseases – from prediction to management and prognosis. On the other hand, enough evidence exists to assume that hypertensive disorders of pregnancy share a certain connection with cardiovascular diseases – from common risk factors and underlying mechanisms to the presence of a higher risk for women for the development of a great number of cardiovascular diseases, such as arterial hypertension, coronary atherosclerosis, stroke, peripheral artery disease, venous thromboembolism, and even a higher cardiovascular mortality. The key to a better understanding of the unfavorable cardiovascular profile of women with a hypertensive disorder of pregnancy may lie in their assessment with biomarkers, typically used in the field of cardiology. In this review, we have included studies investigating the use of cardiovascular biomarkers during or after a hypertensive pregnancy, namely, natriuretic peptides, high-sensitivity cardiac troponins, growth/differentiation factor 15 (GDF15), soluble suppression of tumorigenicity-2 (sST2), and galectin-3.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Eurostat. Cardiovascular Diseases; 2020. Available from: https://www.ec.europa.eu/eurostat/statistics-explained/index.php/cardiovascular_diseases_statistics#deaths_from_cardiovascular_diseases. [Last accessed on 2021 Feb 04]

Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013;25(2):124-32. PMid:23403779

Roberts JM, Hubel CA. The two stage model of preeclampsia: Variations on the theme. Placenta. 2009;30 Suppl A:S32-7. https://doi.org/10.1016/j.placenta.2008.11.009 PMid:19070896

Pankiewicz K, Szczerba E, Maciejewski T, Fijałkowska A. Nonobstetric complications in preeclampsia. Prz Menopauzalny. 2019;18(2):99-109. https://doi.org/10.5114/pm.2019.85785 PMid:31485207

Khalil G, Hameed A. Preeclampsia: Pathophysiology and the maternal-fetal risk. J Hypertens Manag. 2017;3:024.

Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJ. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and Type 2 diabetes mellitus in the mother. Hypertension. 2009;53(6):944-51. https://doi.org/10.1161/hypertensionaha.109.130765 PMid:19433776

Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, et al. Preeclampsia and future cardiovascular health: A systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2):e003497. https://doi.org/10.1161/circoutcomes.116.003497 PMid:28228456

Theilen LH, Fraser A, Hollingshaus MS, Schliep KC, Varner MW, Smith KR, et al. All-cause and cause-specific mortality after hypertensive disease of pregnancy. Obstet Gynecol. 2016;128(2):238-44. https://doi.org/10.1097/aog.0000000000001534 PMid:27400006

Craici I, Wagner S, Garovic VD. Preeclampsia and future cardiovascular risk: Formal risk factor or failed stress test? Ther Adv Cardiovasc Dis. 2008;2(4):249-59. https://doi.org/10.1177/1753944708094227 PMid:19124425

Choi SK, Shin JC, Park YG, Park IY, Kwon JY, Ko HS, et al. The efficacy of peripartum transthoracic echocardiography in women with preeclampsia. Pregnancy Hypertens. 2017;10:187‑91. https://doi.org/10.1016/j.preghy.2017.05.002 PMid:29153677

Palei AC, Spradley FT, Warrington JP, George EM, Granger JP. Pathophysiology of hypertension in pre-eclampsia: A lesson in integrative physiology. Acta Physiol (Oxf). 2013;208(3):224-33. https://doi.org/10.1111/apha.12106 PMid:23590594

Fenton M, Burch M. Understanding chronic heart failure. Arch Dis Child. 2007;92(9):812-6. PMid:17715446

Sánchez-Aranguren LC, Prada CE, Riaño-Medina CE, Lopez M. Endothelial dysfunction and preeclampsia: Role of oxidative stress. Front Physiol. 2014;5:372. https://doi.org/10.3389/fphys.2014.00372 PMid:25346691

Harmon AC, Cornelius DC, Amaral LM, Faulkner JL, Cunningham MW Jr., Wallace K, et al. The role of inflammation in the pathology of preeclampsia. Clin Sci (Lond). 2016;130(6):409-19. https://doi.org/10.1042/cs20150702 PMid:26846579

Koenig W. Low-grade inflammation modifies cardiovascular risk even at very low LDL-C levels: Are we aiming for a dual target concept? Circulation. 2018;138(2):150-3. https://doi.org/10.1161/circulationaha.118.035107 PMid:29986958

Wojcik-Baszko D, Charkiewicz K, Laudanski P. Role of dyslipidemia in preeclampsia-a review of lipidomic analysis of blood, placenta, syncytiotrophoblast microvesicles and umbilical cord artery from women with preeclampsia. Prostaglandins Other Lipid Mediat. 2018;139:19-23. https://doi.org/10.1016/j.prostaglandins.2018.09.006 PMid:30248406

Hauth JC, Clifton RG, Roberts JM, Myatt L, Spong CY, Leveno KJ, et al. Maternal insulin resistance and preeclampsia. Am J Obstet Gynecol. 2011;204(4):327.e1-6. PMid:21458622

English FA, Kenny LC, McCarthy FP. Risk factors and effective management of preeclampsia. Integr Blood Press Control. 2015;8:7-12. PMid:25767405

Cao Z, Jia Y, Zhu B. BNP and NT-proBNP as diagnostic biomarkers for cardiac dysfunction in both clinical and forensic medicine. Int J Mol Sci. 2019;20(8):1820. https://doi.org/10.3390/ijms20081820 PMid:31013779

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr., Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America. Circulation. 2017;136(6):e137-61. https://doi.org/10.1161/cir.0000000000000460 PMid:28455343

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC) developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-200. https://doi.org/10.3410/f.718489795.793497182 PMid:27206819

Salah K, Stienen S, Pinto YM, Eurlings LW, Metra M, Bayes-Genis A, et al. Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction. Heart. 2019;105(15):1182-9. https://doi.org/10.1136/heartjnl-2018-314173 PMid:30962192

Palazzuoli A, Beltrami M, Ruocco G, Franci B, Campagna MS, Nuti R. Diagnostic utility of contemporary echo and BNP assessment in patients with acute heart failure during early hospitalization. Eur J Intern Med. 2016;30:43-8. https://doi.org/10.1016/j.ejim.2015.11.031 PMid:26718066

Karakiliç E, Kepez A, Abali G, Coşkun F, Kunt M, Tokgözoğlu L. The relationship between B-type natriuretic peptide levels and echocardiographic parameters in patients with heart failure admitted to the emergency department. Anadolu Kardiyol Derg. 2010;10(2):143-9. https://doi.org/10.5152/akd.2010.040 PMid:20382614

Tschöpe C, Kasner M, Westermann D, Gaub R, Poller WC, Schultheiss HP. The role of NT-proBNP in the diagnostics of isolated diastolic dysfunction: Correlation with echocardiographic and invasive measurements. Eur Heart J. 2005;26(21):2277-84. https://doi.org/10.1093/eurheartj/ehi406 PMid:16014646

Afshani N, Moustaqim-Barrette A, Biccard BM, Rodseth RN, Dyer RA. Utility of B-type natriuretic peptides in preeclampsia: A systematic review. Int J Obstet Anesth. 2013;22(2):96-103. https://doi.org/10.1016/j.ijoa.2012.11.001 PMid:23462297

Alma LJ, Bokslag A, Maas AH, Franx A, Paulus WJ, de Groot CJ. Shared biomarkers between female diastolic heart failure and pre-eclampsia: A systematic review and meta-analysis. ESC Heart Fail. 2017;4(2):88-98. https://doi.org/10.1002/ehf2.12129 PMid:28451444

Szabó G, Molvarec A, Nagy B, Rigó J Jr. Increased B-type natriuretic peptide levels in early-onset versus late-onset preeclampsia. Clin Chem Lab Med. 2014;52(2):281-8. https://doi.org/10.1515/cclm-2013-0307 PMid:23979127

Fayers S, Moodley J, Naidoo DP. Cardiovascular haemodynamics in pre-eclampsia using brain naturetic peptide and tissue Doppler studies. Cardiovasc J Afr. 2013;24(4):130-6. https://doi.org/10.5830/cvja-2013-023 PMid:24217044

Ghomian N, Vakilian F, Shahri B, Rostaminejad V, Khadem-Rezaiyan M. Can brain natriuretic peptide predict cardiovascular complications in severe preeclampsia? A case-control study. Int J Reprod Biomed. 2019;17(4):271-8. https://doi.org/10.18502/ijrm.v17i4.4552 PMid:31435608

Tihtonen KM, Kööbi T, Vuolteenaho O, Huhtala HS, Uotila JT. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol. 2007;196(4):328.e1-7. https://doi.org/10.1016/j.ajog.2006.11.033 PMid:17403408

Sadlecki P, Grabiec M, Walentowicz-Sadlecka M. Prenatal clinical assessment of NT-proBNP as a diagnostic tool for preeclampsia, gestational hypertension and gestational diabetes mellitus. PLoS One. 2016;11(9):e0162957. https://doi.org/10.1371/journal.pone.0162957 PMid:27685993

Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e51.

Ottani F, Galvani M, Nicolini FA, Ferrini D, Pozzati A, Di Pasquale G, et al. Elevated cardiac troponin levels predict the risk of adverse outcome in patients with acute coronary syndromes. Am Heart J. 2000;140(6):917-27. https://doi.org/10.1067/mhj.2000.111107 PMid:11099996

Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, Hoogeveen RC, et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the atherosclerosis risk in communities study. Circulation. 2011;123(13):1367-76. https://doi.org/10.1161/circulationaha.110.005264 PMid:21422391

Pergialiotis V, Prodromidou A, Frountzas M, Perrea DN, Papantoniou N. Maternal cardiac troponin levels in preeclampsia: A systematic review. J Matern Fetal Neonatal Med. 2016;29(20):3386-90. https://doi.org/10.3109/14767058.2015.1127347 PMid:26745550

Fleming SM, O’Gorman T, Finn J, Grimes H, Daly K, Morrison JJ. Cardiac troponin I in pre-eclampsia and gestational hypertension. BJOG. 2000;107(11):1417-20. https://doi.org/10.1111/j.1471-0528.2000.tb11658.x PMid:11117772

Morton A, Morton A. High sensitivity cardiac troponin I levels in preeclampsia. Pregnancy Hypertens. 2018;13:79-82. https://doi.org/10.1016/j.preghy.2018.04.020 PMid:30177077

Ravichandran J, Woon SY, Quek YS, Lim YC, Noor EM, Suresh K, et al. High-sensitivity cardiac troponin I levels in normal and hypertensive pregnancy. Am J Med. 2019;132(3):362-6. https://doi.org/10.1016/j.amjmed.2018.11.017 PMid:30503877

Joyal D, Leya F, Koh M, Besinger R, Ramana R, Kahn S, et al. Troponin I levels in patients with preeclampsia. Am J Med. 2007;120(9):819.e13-4. https://doi.org/10.1016/j.amjmed.2006.05.068 PMid:17765054

Umazume T, Yamada S, Yamada T, Ishikawa S, Furuta I, Iwano H, et al. Association of peripartum troponin I levels with left ventricular relaxation in women with hypertensive disorders of pregnancy. Open Heart. 2018;5(2):e000829. https://doi.org/10.1136/openhrt-2018-000829 PMid:30245837

Muijsers HE, Westermann D, Birukov A, van der Heijden OW, Drost JT, Kräker K, et al. High-sensitivity cardiac troponin I in women with a history of early-onset preeclampsia. J Hypertens. 2020;38(10):1948-54. https://doi.org/10.1097/hjh.0000000000002497 PMid:32890270

Homsak E, Gruson D. Soluble ST2: A complex and diverse role in several diseases. Clin Chim Acta. 2020;507:75-87. https://doi.org/10.1016/j.cca.2020.04.011 PMid:32305537

Sanada S, Hakuno D, Higgins L, Schreiter ER, McKenzie AN, Lee RT. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007;117(6):1538-49. https://doi.org/10.1172/jci30634 PMid:17492053

Daniels LB, Clopton P, Iqbal N, Tran K, Maisel AS. Association of ST2 levels with cardiac structure and function and mortality in outpatients. Am Heart J. 2010;160(4):721-8. https://doi.org/10.1016/j.ahj.2010.06.033 PMid:20934567

Pratama RS, Hartopo AB, Anggrahini DW, Dewanto VC, Dinarti LK. Serum soluble suppression of tumorigenicity-2 level associates with severity of pulmonary hypertension associated with uncorrected atrial septal defect. Pulm Circ. 2020;10(2):2045894020915832. https://doi.org/10.1177/2045894020915832 PMid:32518620

Zhang Y, Fan Z, Liu H, Ma J, Zhang M. Correlation of plasma soluble suppression of tumorigenicity-2 level with the severity and stability of coronary atherosclerosis. Coron Artery Dis. 2020;31(7):628-35. https://doi.org/10.1097/mca.0000000000000851 PMid:32040025

Gaggin HK, Szymonifka J, Bhardwaj A, Belcher A, De Berardinis B, Motiwala S, et al. Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highlysensitive troponin T measurements in patients with chronic heart failure. JACC Heart Fail. 2014;2(1):65-72. https://doi.org/10.1016/j.jchf.2013.10.005 PMid:24622120

AbouEzzeddine OF, McKie PM, Dunlay SM, Stevens SR, Felker GM, Borlaug BA, et al. Suppression of tumorigenicity 2 in heart failure with preserved ejection fraction. J Am Heart Assoc. 2017;6(2):e004382. https://doi.org/10.1161/jaha.116.004382 PMid:28214792

Romero R, Chaemsaithong P, Tarca AL, Korzeniewski SJ, Maymon E, Pacora P, et al. Maternal plasma-soluble ST2 concentrations are elevated prior to the development of early and late onset preeclampsia-a longitudinal study. J Matern Fetal Neonatal Med. 2018;31(4):418-32. https://doi.org/10.1080/14767058.2017.1286319 PMid:28114842

Stampalija T, Chaiworapongsa T, Romero R, Chaemsaithong P, Korzeniewski SJ, Schwartz AG, et al. Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia. J Matern Fetal Neonatal Med. 2013;26(14):1359‑70. https://doi.org/10.3109/14767058.2013.784256 PMid:23488689

Mugerli S, Ambrožič J, Geršak K, Lučovnik M. Elevated soluble-ST2 concentrations in preeclampsia correlate with echocardiographic parameters of diastolic dysfunction andreturn to normal values one year after delivery. J Matern Fetal Neonatal Med. 2021;34(3):379-85. https://doi.org/10.1080/14767058.2019.1609934 PMid:31056999

de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: A novel mediator of heart failure development and progression. Eur J Heart Fail. 2009;11(9):811‑7. https://doi.org/10.1093/eurjhf/hfp097 PMid:19648160

Frunza O, Russo I, Saxena A, Shinde AV, Humeres C, Hanif W, et al. Myocardial galectin-3 expression is associated with remodeling of the pressure-overloaded heart and may delay the hypertrophic response without affecting survival, dysfunction, and cardiac fibrosis. Am J Pathol. 2016;186(5):1114-27. https://doi.org/10.1016/j.ajpath.2015.12.017 PMid:26948424

Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110(19):3121-8. https://doi.org/10.1161/01.cir.0000147181.65298.4d PMid:15520318

Meijers WC, Januzzi JL, deFilippi C, Adourian AS, Shah SJ, van Veldhuisen DJ, et al. Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: A pooled analysis of 3 clinical trials. Am Heart J. 2014;167(6):853-60.e4. https://doi.org/10.1016/j.ahj.2014.02.011 PMid:24890535

Mazurek JA, Horne BD, Saeed W, Sardar MR, Zolty R. Galectin-3 levels are elevated and predictive of mortality in pulmonary hypertension. Heart Lung Circ. 2017;26(11):1208‑15. https://doi.org/10.1016/j.hlc.2016.12.012 PMid:28242288

Nar G, Aksan G, Gorgulu O, Inci S, Soylu K, Ozdemir M, et al. Galectin-3 as a novel biomarker for the diagnosis of essential hypertension with left ventricular hypertrophy. J Exp Clin Med. 2016;33:123-8.

Zaborska B, Sygitowicz G, Smarż K, Pilichowska-Paszkiet E, Budaj A. Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity. Sci Rep. 2020;10(1):16682. https://doi.org/10.1038/s41598-020-73634-8 PMid:33028850

Taha AS, Zahraei Z, Al-Hakeim H. Serum apelin and galectin-3 in preeclampsia in Iraq. Preprints. 2019;2019:100270. https://doi.org/10.20944/preprints201910.0270.v1

Jeschke U, Mayr D, Schiessl B, Mylonas I, Schulze S, Kuhn C, et al. Expression of galectin-1, -3 (gal-1, gal-3) and the Thomsen-Friedenreich (TF) antigen in normal, IUGR, preeclamptic and HELLP placentas. Placenta. 2007;28(11-12):1165-73. https://doi.org/10.1016/j.placenta.2007.06.006

Demmert M, Faust K, Bohlmann MK, Tröger B, Göpel W, Herting E, et al. Galectin-3 in cord blood of term and preterm infants. Clin Exp Immunol. 2012;167(2):246-51. https://doi.org/10.1111/j.1365-2249.2011.04509.x PMid:22236000

Breit SN, Johnen H, Cook AD, Tsai VW, Mohammad ME, Kuffner T, et al. The TGF-β superfamily cytokine, MIC-1/GDF15: A pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors. 2011;29(5):187-95. https://doi.org/10.3109/08977194.2011.607137 PMid:21831009

Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, et al. The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res. 2006;98(3):351-60. https://doi.org/10.1161/01.res.0000202805.73038.48 PMid:16397141

Schlittenhardt D, Schober A, Strelau J, Bonaterra GA, Schmiedt W, Unsicker K, et al. Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions. Cell Tissue Res. 2004;318(2):325-33. https://doi.org/10.1007/s00441-004-0986-3 PMid:15459768

Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, et al. Serial measurement of growth-differentiation factor-15 in heart failure: Relation to disease severity and prognosis in the valsartan heart failure trial. Circulation. 2010;122(14):1387-95. https://doi.org/10.1161/circulationaha.109.928846 PMid:20855664

Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, et al. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem. 2007;53(2):284-91. https://doi.org/10.1373/clinchem.2006.076828 PMid:17185363

Chen Q, Wang Y, Zhao M, Hyett J, da Silva Costa F, Nie G. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases. Cytokine. 2016;83:226-30. https://doi.org/10.1016/j.cyto.2016.05.002 PMid:27173615

Sugulle M, Dechend R, Herse F, Weedon-Fekjaer MS, Johnsen GM, Brosnihan KB, et al. Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus. Hypertension. 2009;54(1):106-12. https://doi.org/10.1161/hypertensionaha.109.130583 PMid:19470878

Yuksel TI, Mathyk BA, Cetin BA, Turhan U, Okumus ZG, Yildirim GY, et al. Maternal levels of growth differentiation factor-15 in patients with preeclampsia. Hypertens Pregnancy. 2018;37(4):192-6. https://doi.org/10.1080/10641955.2018.1524477 PMid:30295110