Adrenomedullin and Endothelin-1 Are Associated with Myocardial Injury and Death in Septic Shock Patients

Overview

Journal Crit Care

Specialty Critical Care

Date 2016 Jun 11

PMID 27282767

Citations 19

Authors

Oscar H M Lundberg

Lill Bergenzaun

Jorgen Ryden

Mari Rosenqvist

Olle Melander

Michelle S Chew

Affiliations

Soon will be listed here.

Abstract

Background: Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality.

Methods: A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated.

Results: Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold.

Conclusions: MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.

Citing Articles

Early high-sensitivity troponin elevation and short-term mortality in sepsis: a systematic review with meta-analysis.

Gajardo A, Ferriere-Steinert S, Valenzuela Jimenez J, Heskia Araya S, Kouyoumdjian Carvajal T, Ramos-Rojas J Crit Care. 2025; 29(1):76.

PMID: 39953561 PMC: 11829436. DOI: 10.1186/s13054-025-05249-2.

Biomarkers in cardiogenic shock: old pals, new friends.

Jozwiak M, Lim S, Si X, Monnet X Ann Intensive Care. 2024; 14(1):157.

PMID: 39414666 PMC: 11485002. DOI: 10.1186/s13613-024-01388-x.

Utility of Adrenomedullin in Predicting Outcomes in Patients with Acute Febrile Illness in the Tropics: A Prospective Observational Study.

Tirlangi P, Ravindra P, Bhat R, Belle V, Chaudhuri S, Bhat A Am J Trop Med Hyg. 2024; 111(6):1338-1342.

PMID: 39378871 PMC: 11619512. DOI: 10.4269/ajtmh.24-0301.

The Role of Adrenomedullin as a Predictive Marker of the Risk of Death and Adverse Clinical Events: A Review of the Literature.

Sacco M, Gualtieri S, Cordasco F, Tarallo A, Verrina M, Princi A J Clin Med. 2024; 13(16).

PMID: 39200990 PMC: 11355278. DOI: 10.3390/jcm13164847.

The role of proadrenomedullin, interleukin 6 and CD64 in the diagnosis and prognosis of septic shock.

Turan Y BMC Anesthesiol. 2023; 23(1):278.

PMID: 37592204 PMC: 10433549. DOI: 10.1186/s12871-023-02237-3.

References

Pittet J, Morel D, Hemsen A, Gunning K, Lacroix J, Suter P . Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis. Ann Surg. 1991; 213(3):261-4. PMC: 1358338. DOI: 10.1097/00000658-199103000-00014. View

Samson W, Resch Z, Murphy T, Vargas T, Schell D . Adrenomedullin: Is There Physiological Relevance in the Pathology and Pharmacology?. News Physiol Sci. 2001; 14:255-259. DOI: 10.1152/physiologyonline.1999.14.6.255. View

Wang P, Ba Z, Cioffi W, Bland K, Chaudry I . The pivotal role of adrenomedullin in producing hyperdynamic circulation during the early stage of sepsis. Arch Surg. 1998; 133(12):1298-304. DOI: 10.1001/archsurg.133.12.1298. View

Reynolds T, Cecconi M, Collinson P, Rhodes A, Grounds R, Hamilton M . Raised serum cardiac troponin I concentrations predict hospital mortality in intensive care unit patients. Br J Anaesth. 2012; 109(2):219-24. DOI: 10.1093/bja/aes141. View

Fenhammar J, Andersson A, Forestier J, Weitzberg E, Sollevi A, Hjelmqvist H . Endothelin receptor A antagonism attenuates renal medullary blood flow impairment in endotoxemic pigs. PLoS One. 2011; 6(7):e21534. PMC: 3132177. DOI: 10.1371/journal.pone.0021534. View

Brouwers F, de Boer R, van der Harst P, Struck J, de Jong P, de Zeeuw D . Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population. Heart. 2012; 98(18):1348-53. DOI: 10.1136/heartjnl-2012-302390. View

Bergenzaun L, Ohlin H, Gudmundsson P, During J, Willenheimer R, Chew M . High-sensitive cardiac Troponin T is superior to echocardiography in predicting 1-year mortality in patients with SIRS and shock in intensive care. BMC Anesthesiol. 2012; 12:25. PMC: 3524030. DOI: 10.1186/1471-2253-12-25. View

Rosjo H, Varpula M, Hagve T, Karlsson S, Ruokonen E, Pettila V . Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome. Intensive Care Med. 2010; 37(1):77-85. PMC: 3020309. DOI: 10.1007/s00134-010-2051-x. View

Thygesen K, Alpert J, Jaffe A, Chaitman B, White H, Katus H . Third universal definition of myocardial infarction. Circulation. 2012; 126(16):2020-35. DOI: 10.1161/CIR.0b013e31826e1058. View

10.

Bergenzaun L, Gudmundsson P, Ohlin H, During J, Ersson A, Ihrman L . Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care. Crit Care. 2011; 15(4):R200. PMC: 3387642. DOI: 10.1186/cc10368. View

11.

Guignant C, Voirin N, Venet F, Poitevin F, Malcus C, Bohe J . Assessment of pro-vasopressin and pro-adrenomedullin as predictors of 28-day mortality in septic shock patients. Intensive Care Med. 2009; 35(11):1859-67. DOI: 10.1007/s00134-009-1610-5. View

12.

Alam M, Wardell J, Andersson E, Samad B, Nordlander R . Effects of first myocardial infarction on left ventricular systolic and diastolic function with the use of mitral annular velocity determined by pulsed wave doppler tissue imaging. J Am Soc Echocardiogr. 2000; 13(5):343-52. DOI: 10.1016/s0894-7317(00)70003-4. View

13.

Wang P . Andrenomedullin and cardiovascular responses in sepsis. Peptides. 2002; 22(11):1835-40. DOI: 10.1016/s0196-9781(01)00534-4. View

14.

Christ-Crain M, Morgenthaler N, Struck J, Harbarth S, Bergmann A, Muller B . Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care. 2005; 9(6):R816-24. PMC: 1414007. DOI: 10.1186/cc3885. View

15.

Lim W, Qushmaq I, Devereaux P, Heels-Ansdell D, Lauzier F, Ismaila A . Elevated cardiac troponin measurements in critically ill patients. Arch Intern Med. 2006; 166(22):2446-54. DOI: 10.1001/archinte.166.22.2446. View

16.

Nicholls M, Lainchbury J, Lewis L, McGregor D, Richards A, Troughton R . Bioactivity of adrenomedullin and proadrenomedullin N-terminal 20 peptide in man. Peptides. 2002; 22(11):1745-52. DOI: 10.1016/s0196-9781(01)00508-3. View

17.

Khan S, OBrien R, Struck J, Quinn P, Morgenthaler N, Squire I . Prognostic value of midregional pro-adrenomedullin in patients with acute myocardial infarction: the LAMP (Leicester Acute Myocardial Infarction Peptide) study. J Am Coll Cardiol. 2007; 49(14):1525-32. DOI: 10.1016/j.jacc.2006.12.038. View

18.

McLean A, Huang S . Cardiac biomarkers in the intensive care unit. Ann Intensive Care. 2012; 2:8. PMC: 3313856. DOI: 10.1186/2110-5820-2-8. View

19.

Matos J, Kronzon I, Panagopoulos G, Perk G . Mitral annular plane systolic excursion as a surrogate for left ventricular ejection fraction. J Am Soc Echocardiogr. 2012; 25(9):969-74. DOI: 10.1016/j.echo.2012.06.011. View

20.

Konrad D, Haney M, Johansson G, Wanecek M, Weitzberg E, Oldner A . Cardiac effects of endothelin receptor antagonism in endotoxemic pigs. Am J Physiol Heart Circ Physiol. 2007; 293(2):H988-96. DOI: 10.1152/ajpheart.01023.2006. View