Skip to main content

Advertisement

Log in

Novel Biomarkers to Detect Target Organ Damage in Acute Hypertension

  • Hypertension and Emergency Medicine (T Rainer and P Levy, Section Editors)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Early lowering of blood pressure is advised for patients with severe hypertension associated with signs of impending or progressive organ damage, whereas aggressive treatment is not recommended in patients with asymptomatic severe hypertension. As treatment goals for asymptomatic hypertension and true hypertensive emergency drastically differ, it is essential to identify patients with evidence of impending or progressive organ damage. Biomarkers may assist providers in identifying high-risk patients who would benefit from early blood pressure reduction.

Recent Findings

In this review, we discuss both currently available and investigational biomarkers that may help identify patients who might benefit from more aggressive therapy. We focus on serum and urinary biomarkers associated with acute cardiovascular, renal, and cerebrovascular damage.

Summary

There is a dearth of literature regarding the use of biomarkers to assess acute hypertension-related target organ damage. We are primarily forced to draw conclusions on the use of biomarkers from studies of related conditions such as acute heart failure. Further research is needed on the clinical significance of abnormal levels of novel biomarkers of renal, cardiac, and cerebral dysfunction in the setting of severe hypertension, particularly in those patients without overt clinical signs of organ failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Chobanian AV, Bakris GL, Black HR, National High Blood Pressure Education Program Coordinating Committee, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52. https://doi.org/10.1161/01.HYP.0000107251.49515.c2.

    Article  CAS  PubMed  Google Scholar 

  2. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281–357. https://doi.org/10.1097/01.hjh.0000431740.32696.cc.

    Article  CAS  PubMed  Google Scholar 

  3. McNaughton CD, Self WH, Zhu Y, Janke AT, Storrow AB, Levy P. Incidence of hypertension-related emergency department visits in the United States, 2006 to 2012. Am J Cardiol. 2015;116(11):1717–23. https://doi.org/10.1016/j.amjcard.2015.09.007.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Janke AT, CD MN, Brody AM, Welch RD, Levy PD. Trends in the incidence of hypertensive emergencies in US emergency departments from 2006 to 2013. J Am Heart Assoc. 2016 Dec 5;5(12)

  5. Wolf SJ, Lo B, Shih RD, Smith MD, Fesmire FM, American College of Emergency Physicians Clinical Policies Committee. Clinical policy: critical issues in the evaluation and management of adult patients in the emergency department with asymptomatic elevated blood pressure. Ann Emerg Med. 2013;62(1):59–68. https://doi.org/10.1016/j.annemergmed.2013.05.012.

    Article  PubMed  Google Scholar 

  6. •• Levy PD, Mahn JJ, Miller J, et al. Blood pressure treatment and outcomes in hypertensive patients without acute target organ damage: a retrospective cohort. Am J Emerg Med. 2015;33(9):1219–24. This paper demonstrated that, regardless of the degree of blood pressure elevation, patients presenting to the emergency department with severe hypertension without organ damage did not derive benefit from early initiation of antihypertensive therapy.

    Article  PubMed  Google Scholar 

  7. Mahajan N, Mehta Y, Rose M, et al. Elevated troponin level is not synonymous with myocardial infarction. Int J Cardiol. 2006;111:442–9.

    Article  PubMed  Google Scholar 

  8. Taniguchi R, Sato Y, Nishio Y, et al. Measurements of baseline and follow-up concentrations of cardiac troponin-T and brain natriuretic peptide in patients with heart failure from various etiologies. Heart Vessel. 2006;21:344–9.

    Article  Google Scholar 

  9. Ammann P, Maggiorini M, Bertel O, Haenseler E, Joller-Jemelka HI, Oechslin E, et al. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. J Am Coll Cardiol. 2003;41(11):2004–9. https://doi.org/10.1016/S0735-1097(03)00421-2.

    Article  CAS  PubMed  Google Scholar 

  10. Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation. 2007;116(4):427–33. https://doi.org/10.1161/CIRCULATIONAHA.106.680421.

    Article  CAS  PubMed  Google Scholar 

  11. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation. 2002;106(23):2941–5. https://doi.org/10.1161/01.CIR.0000041254.30637.34.

    Article  CAS  PubMed  Google Scholar 

  12. Su Y-C, Huang K-F, Yang F-Y, Lin S-K. Elevation of troponin I in acute ischemic stroke. PeerJ. 2016;4:e1866.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kertai MD, Boersma E, Klein J, et al. Long-term prognostic value of asymptomatic cardiac troponin T elevations in patients after major vascular surgery. Eur J Vasc Endovasc Surg. 2004;28:59–66.

    Article  CAS  PubMed  Google Scholar 

  14. Pattanshetty DJ, Bhat PK, Aneja A, Pillai DP. Elevated troponin predicts long-term adverse cardiovascular outcomes in hypertensive crisis: a retrospective study. J Hypertens. 2012;30(12):2410–5. https://doi.org/10.1097/HJH.0b013e3283599b4f.

    Article  CAS  PubMed  Google Scholar 

  15. • Afonso L, Bandaru H, Rathod A, Badheka A, Kizilbash A, et al. Prevalence, determinants, and clinical significance of cardiac troponin-I elevation in individuals admitted for a hypertensive emergency. J Clin Hypertens. 2011;13:551–6. This study is notable for both highlighting a very high mortality rate among patients with hypertensive emergency and also for demonstrating that elevated troponin levels in acute hypertension, absent acute coronary syndrome, may not be independently associated with increased mortality.

    Article  CAS  Google Scholar 

  16. Maludum O, Shah M, Mezue K, Biso S, Rodriguez-Ziccardi M, et al. Factors that influence decision for ischemic work-up in hypertensive emergency. Int J Cardiol. 2016 Jul 1;214:331–2.

    Article  PubMed  Google Scholar 

  17. Miller WL, Hartman KA, Burritt MF, Grill DE, Rodeheffer RJ, Burnett JC, et al. Serial biomarker measurements in ambulatory patients with chronic heart failure: the importance of change over time. Circulation. 2007;116(3):249–57. https://doi.org/10.1161/CIRCULATIONAHA.107.694562.

    Article  CAS  PubMed  Google Scholar 

  18. Pascual-Figal DA, Manzano-Fernández S, Boronat M, Casas T, Garrido IP, et al. Soluble ST2, high-sensitivity troponin T- and N-terminal pro-B-type natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure. Eur J Heart Fail. 2011;13(7):718.

    Article  CAS  PubMed  Google Scholar 

  19. Peacock WF, De Marco T, Fonarow GC, et al. Cardiac troponin and outcomes in acute heart failure. N Engl J Med. 2008;258:2117–26.

    Article  Google Scholar 

  20. Niederkofler EE, Kierna UA, O’Rear J, et al. Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure. Circ Heart Fail. 2008;1(4):258–64. https://doi.org/10.1161/CIRCHEARTFAILURE.108.790774.

    Article  CAS  PubMed  Google Scholar 

  21. Roberts E, Ludman AJ, Dworzynski K, Al-Mohammad A, Cowie MR, McMurray JJ, et al. The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting. BMJ. 2015;350(mar04 22):h910. https://doi.org/10.1136/bmj.h910.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fonarow GC, Peacock WF, Phillips CO, Givertz MM, Lopatin M, ADHERE Scientific Advisory Committee and Investigators. Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure. J Am Coll Cardiol. 2007;49(19):1943–50. https://doi.org/10.1016/j.jacc.2007.02.037.

    Article  CAS  PubMed  Google Scholar 

  23. •• Peacock F, Amin A, Granger CB, Pollack CV, Levy P, et al. Hypertensive heart failure: patient characteristics, treatment, and outcomes. Am J Emerg Med. 2011;(8):855–62. This retrospective study of over 12,000 patients is perhaps the largest and best study on the prognostic significance of abnormal biomarkers (natriuretic peptides) in patients with hypertensive emergency.

  24. Kato J, Tsuruda T, Kita T, Kitamura K, Eto T. Adrenomedullin: a protective factor for blood vessels. Arteriorscler Thromb Vasc Biol. 2005;25:2480–7.

    Article  CAS  Google Scholar 

  25. Funke-Kaiser A, Mann K, Colquhoun D, et al. Mid- regional proadrenomedullin and its change predicts recurrent major coronary events and heart failure in stable coronary heart disease patients: the LIPID study. Int J Cardiol. 2014;172:411–8.

    Article  PubMed  Google Scholar 

  26. Suberviola B, Castellanos-Ortega A, Llorca J, Ortiz F, Iglesias D, Prieto B. Prognostic value of proad- renomedullin in severe sepsis and septic shock patients with community-acquired pneumonia. Swiss Med Wkly. 2012;142:w13542.

    PubMed  Google Scholar 

  27. Huang DT, Angus DC, Kellum JA, Pugh NA, Weissfeld LA, Struck J, et al. Midregional proadrenomedullin as a prognostic tool in community-acquired pneumonia. Chest. 2009;136(3):823–31. https://doi.org/10.1378/chest.08-1981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. • Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P, et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in ACute Heart failure) trial. J Am Coll Cardiol. 2010;55:2062–76. The BACH trial highlighted the potential prognostic implications of both MR-ProADM and Copeptin in the acute care setting.

    Article  CAS  PubMed  Google Scholar 

  29. Shah KS, Marston NA, Mueller C, Neath SX, Christenson RH, McCord J, et al. Midregional proadrenomedullin predicts mortality and major adverse cardiac events in patients presenting with chest pain: results from the CHOPIN trial. Acad Emerg Med. 2015;22(5):554–63. https://doi.org/10.1111/acem.12649.

    Article  PubMed  Google Scholar 

  30. Maisel A, Xue Y, Shah K, Mueller C, Nowak R, et al. Increased 90-day mortality in patients with acute heart failure with elevated copeptin; secondary results from the Biomarkers in Acute Heart Failure (BACH) study. Circ Heart Fail. 2011;4:613–20.

    Article  CAS  PubMed  Google Scholar 

  31. Nickel CH, Bingisser R, Morgenthaler NG. The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department. BMC Med. 2012;10(1):7. https://doi.org/10.1186/1741-7015-10-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Maisel A, Mueller C, Neath SX, Christenson RH, Morgenthaler NG. Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction). J Am Coll Cardiol. 2013;62(2):150–60.

    Article  CAS  PubMed  Google Scholar 

  33. Wildi K, Zellweger C, Twerenbold R, Jaeger C, Reichlin T. Incremental value of copeptin to highly sensitive cardiac troponin I for rapid rule-out of myocardial infarction. Int J Cardiol. 2015;190(1):170–6. https://doi.org/10.1016/j.ijcard.2015.04.133.

    Article  PubMed  Google Scholar 

  34. Villacorta H, Maisel AS. Soluble ST2 testing: a promising biomarker in the management of heart failure. Arq Bras Cardiol. 2016;106(2):145–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Gaggin HK, Januzzi JL. Cardiac biomarkers and heart failure. http://www.acc.org/latest-in-cardiology/articles/2015/02/09/13/00/cardiac-biomarkers-and-heart-failure. Published Feb 10, 2015. Accessed 29 June 2017.

  36. Parikh R, Seliger S, Christenson R, et al. Soluble ST2 for prediction of heart failure and cardiovascular death in an elderly, community-dwelling population. J Am Heart Assoc. 2016;5:3003188.

    Article  Google Scholar 

  37. Januzzi J, Peacock WF, Maisel AS, et al. Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study. J Am Coll Cardiol. 2007;50(7):607–13. https://doi.org/10.1016/j.jacc.2007.05.014.

    Article  CAS  PubMed  Google Scholar 

  38. • Derhaschnig U, Testori C, Riedmueller E, et al. Decreased renal function in hypertensive emergencies. J Hum Hypertens. 2014;28(7):427–31. This is one of only a few studies to specifically address the use of urinary biomarkers (NGAL) in the setting of hypertensive emergency in the emergency department.

    Article  CAS  PubMed  Google Scholar 

  39. Coca SG, Yalavarthy R, Concato J, Parikh CR. Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int. 2008;73(9):1008–16. https://doi.org/10.1038/sj.ki.5002729.

    Article  CAS  PubMed  Google Scholar 

  40. Ferguson TW, Komenda P, Tangri N. Cystatin C as a biomarker for estimating glomerular filtration rate. Curr Opin Nephrol Hypertens. 2015;24(3):295–300. https://doi.org/10.1097/MNH.0000000000000115.

    Article  CAS  PubMed  Google Scholar 

  41. Garcia-Carretero R, Vigil-Medina L, Barquero-Perez O, Goya-Esteban R, Mora-Jimenez, et al. Cystatin C as a predictor of cardiovascular outcomes in a hypertensive population. J Hum Hyperten. 2017;31(12):801–7. https://doi.org/10.1038/jhh.2017.68.

    Article  CAS  Google Scholar 

  42. Soto K, Coelho S, Rodrigues B, Martin H, Frade F, et al. Cystatin C as a marker of acute kidney injury in the emergency department. Clin J Am Soc Nephrol. 2010 Oct;5(10):1745–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis. 2011 Sep;58(3):356–65. https://doi.org/10.1053/j.ajkd.2011.02.389.

    Article  CAS  PubMed  Google Scholar 

  44. Murty MSN, Sharma UK, Pandey VB, Kankare SB. Serum cystatin C as a marker of renal function in detection of early acute kidney injury. Indian J Nephrol. 2013;23(3):180–3. https://doi.org/10.4103/0971-4065.111840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bolignano D, Donato V, Coppolino G, Campo SC, Buemi A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008 Sep;52(3):595–605. https://doi.org/10.1053/j.ajkd.2008.01.020.

    Article  CAS  PubMed  Google Scholar 

  46. • Nickolas TL, O'Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med. 2008;148:810–9. The results of this study suggest that NGAL is highly predictive of developing acute kidney injury and also shows promise in discriminating acute kidney injury from chronic/non-progressive renal disease.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Corbacioglu SK, Cevik Y, Akinci E, Uzunosmanoglu H, Dagar S, et al. Value of plasma neutrophil gelatinase-associated lipocalin (NGAL) in distinguishing between acute kidney injury (AKI) and chronic kidney disease (CKD). Turk J Emerg Med. 2017;17(3):85–8.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Palazzuoli A, Ruocco G, Pellegrini M, De Gori C, Del Castillo G, et al. Comparison of neutrophil gelatinase-associated lipocalin versus B-type natriuretic peptide and cystatin C to predict early acute kidney injury and outcome in patients with acute heart failure. Am J Cardiol. 2015 Jul 1;116(1):104–11.

    Article  CAS  PubMed  Google Scholar 

  49. Mårtensson J, Bellomo R. The rise and fall of NGAL in acute kidney injury. Blood Purif. 2014;37(4):304–10. https://doi.org/10.1159/000364937.

    Article  PubMed  Google Scholar 

  50. Haase M, Mertens PR. Biomarkers: more than just markers! Nephrol Dial Transplant. 2015 Jan;30(1):33–8. https://doi.org/10.1093/ndt/gfu085.

    Article  PubMed  Google Scholar 

  51. Huang Y, Don-Wauchope AC. The clinical utility of kidney injury molecule 1 in the prediction, diagnosis and prognosis of acute kidney injury: a systematic review. Inflamm Allergy Drug Targets. 2011;10(4):260–71. https://doi.org/10.2174/187152811796117735.

    Article  CAS  PubMed  Google Scholar 

  52. Shao X, Tian L, Xu W, Zhang Z, Wang C, Qi C, et al. Diagnostic value of urinary kidney injury molecule 1 for acute kidney injury: a meta-analysis. PLoS One. 2014;9(1):e84131. https://doi.org/10.1371/journal.pone.0084131.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kadioglu T, Uzunlulu M, Yigit Kaya S, Oguz A, Gonenli G, Isbilen B, et al. Urinary kidney injury molecule-1 levels as a marker of early kidney injury in hypertensive patients. Minerva Urol Nefrol. 2016;68(5):456–61.

    PubMed  Google Scholar 

  54. Bustamante A, Lopez-Cancio E, Pich S, Panalba A, Giralt D, et al. Blood biomarkers for the early diagnosis of stroke: the Stroke-Chip study. Stroke. 2017;48(9):2419–25.

    Article  CAS  PubMed  Google Scholar 

  55. Karabacak M, Yigit M, Turkdogan KA, Yigit E, Selek S. Is signal peptide-CUB-EGF domain-containing protein1 a diagnostic biomarker in patients with hypertensive crises. Clin Hemorheol Microcirc. 2015;61(3):513–22. https://doi.org/10.3233/CH-141917.

    Article  CAS  PubMed  Google Scholar 

  56. Haapaniemi E, Tatlisumak T. Is D-dimer helpful in evaluating stroke patients? A systematic review. Acta Neurol Scand. 2009;119(3):141–50. https://doi.org/10.1111/j.1600-0404.2008.01081.x.

    Article  CAS  PubMed  Google Scholar 

  57. Xu Q, Tian Y, Peng H, Li H. Copeptin as a biomarker for prediction of prognosis of acute ischemic stroke and transient ischemic attack: a meta-analysis. Hypertens Res. 2017;40(5):465–71. https://doi.org/10.1038/hr.2016.165.

    Article  CAS  PubMed  Google Scholar 

  58. Blum CA, Winzeler B, Nigro N, Schuetz P, Biethahn S, et al. Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study. J Headache Pain. 2017;18(1):21.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Bannay A, Husain A, Bohm M, Wagenpfeil S. Outcomes after hypertensive crisis: comparison between diabetics and nondiabetics. IJC Metab Endocr. 2015;7:25–30.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen Boone.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Hypertension and Emergency Medicine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Boone, S., Kuo, D. Novel Biomarkers to Detect Target Organ Damage in Acute Hypertension. Curr Hypertens Rep 20, 21 (2018). https://doi.org/10.1007/s11906-018-0818-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-018-0818-6

Keywords

Navigation