ST2 cardiac biomarker explained

interleukin 1 receptor-like 1
Hgncid:5998
Symbol:IL1RL1
Entrezgene:9173
Omim:601203
Refseq:NM_016232
Uniprot:Q01638
Chromosome:2
Arm:q
Band:12

The ST2 cardiac biomarker (also known as soluble interleukin 1 receptor-like 1) is a protein biomarker of cardiac stress encoded by the IL1RL1 gene. ST2 signals the presence and severity of adverse cardiac remodeling and tissue fibrosis, which occurs in response to myocardial infarction, acute coronary syndrome, or worsening heart failure.[1] [2]

ST2 provides prognostic information that is independent of other cardiac biomarkers such as BNP, NT-proBNP, highly sensitive troponin, GDF-15, and galectin-3.[3] One study indicated that discrimination is independent of age, body mass index, history of heart failure, anemia and impaired kidney function or sex.[4]

Protein

See main article: article and IL1RL1. ST2 is a member of the interleukin 1 receptor family. The ST2 protein has two isoforms and is directly implicated in the progression of cardiac disease: a soluble form (referred to as soluble ST2 or sST2) and a membrane-bound receptor form (referred to as the ST2 receptor or ST2L). When the myocardium is stretched, the ST2 gene is upregulated, increasing the concentration of circulating soluble ST2.[3] The ligand for ST2 is the cytokine interleukin-33 (IL-33). Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, such as an ischemic event, elicits a cardioprotective effect resulting in preserved cardiac function. This cardioprotective IL-33 signal is counterbalanced by the level of soluble ST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of soluble ST2.

Correlation with mortality

Published and peer-reviewed findings indicate that ST2 is a predictor of mortality at presentation.[5] Studies have shown patients with ST2 levels above a clinical threshold consistently have a much higher risk of mortality while, equally important, patients with ST2 levels below threshold have a very low risk of mortality.[6] [7] Although it has been shown that ST2 concentrations correlate with heart failure severity[8] there is no level that perfectly separates patients with and without heart failure for disease diagnosis. However, as a prognostic marker it has been clearly shown that patients are at a higher risk of adverse outcomes when ST2 levels are above a cutoff value of 35 ng/mL.[6]

Patients with ACS

ST2 is a strong predictor of cardiovascular death and risk of developing new heart failure in ST Elevation Myocardial Infarction (STEMI) & NSTE-ACS patients. In patients presenting with Acute Coronary Syndrome (ACS), those in the highest quartile (above 35 ng/ml) have more than 3 times higher risk of cardiovascular death and new heart failure at 30 days, than those in the lower quartiles. At one year, there is a relative risk of 2.3 for adverse outcomes.[9]

ST2 is an active participant in the cardiac remodeling pathway and could identify which patients will respond to Eplerenone, or other therapies that reverse myocardial fibrosis.[10]

Clinical utility

The ST2 test

ST2 is measured by an immunoassay, commercially marketed as the Presage ST2 Assay by Critical Diagnostics of San Diego, California.[14] The assay has Food and Drug Administration approval and a CE Mark.[15]

Notes and References

  1. Shah RV, Januzzi JL . ST2: a novel remodeling biomarker in acute and chronic heart failure . Curr Heart Fail Rep . 7 . 1 . 9–14 . March 2010 . 20425491 . 10.1007/s11897-010-0005-9 . 12213563 .
  2. Rehman SU, Mueller T, Januzzi JL . Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure . J. Am. Coll. Cardiol. . 52 . 18 . 1458–65 . October 2008 . 19017513 . 10.1016/j.jacc.2008.07.042 . free .
  3. doi=10.1016/j.jchf.2012.10.002
  4. Web site: MULTIPLE STUDIES SHOW SUPERIORITY OF CRITICAL DIAGNOSTICS' ST2 OVER BNP, NT-PROBNP AND OTHER HEART FAILURE BIOMARKERS. . October 27, 2016 . July 24, 2015.
  5. Braunwald E . Biomarkers in heart failure . N. Engl. J. Med. . 358 . 20 . 2148–59 . May 2008 . 18480207 . 10.1056/NEJMra0800239 .
  6. Ky B, French B, McCloskey K, Rame JE, McIntosh E, Shahi P, Dries DL, Tang WH, Wu AH, Fang JC, Boxer R, Sweitzer NK, Levy WC, Goldberg LR, Jessup M, Cappola TP . High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure . Circ Heart Fail . 4 . 2 . 180–7 . March 2011 . 21178018 . 3163169 . 10.1161/CIRCHEARTFAILURE.110.958223 .
  7. Kohli P, Bonaca MP, Kakkar R, Kudinova AY, Scirica BM, Sabatine MS, Murphy SA, Braunwald E, Lee RT, Morrow DA . Role of ST2 in Non-ST-Elevation Acute Coronary Syndrome in the MERLIN-TIMI 36 Trial . Clin. Chem. . 58. 1. 257–66. November 2011 . 22096031 . 10.1373/clinchem.2011.173369 . 4277435.
  8. Socrates T, deFilippi C, Reichlin T, Twerenbold R, Breidhardt T, Noveanu M, Potocki M, Reiter M, Arenja N, Heinisch C, Meissner J, Jaeger C, Christenson R, Mueller C . Interleukin family member ST2 and mortality in acute dyspnoea . J. Intern. Med. . 268 . 5 . 493–500 . November 2010 . 20804518 . 10.1111/j.1365-2796.2010.02263.x . 3395239 . free .
  9. Role of ST2 in Non–ST-Elevation Acute Coronary Syndrome in the MERLIN-TIMI 36 Trial . P Kohli . 2012 . 58 . 1 . 257–66 . Clinical Chemistry . 10.1373/clinchem.2011.173369 . 22096031 . 4277435 .
  10. Weir RA, Miller AM, Murphy GE, Clements S, Steedman T, Connell JM, McInnes IB, Dargie HJ, McMurray JJ . Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction . J Am Coll Cardiol . 55 . 3 . 243–50 . January 2010 . 20117403 . 10.1016/j.jacc.2009.08.047. free .
  11. Bayes-Genis A, Pascual-Figal D, Januzzi JL, Maisel A, Casas T, Valdés Chávarri M, Ordóñez-Llanos J . Soluble ST2 monitoring provides additional risk stratification for outpatients with decompensated heart failure . Rev Esp Cardiol . 63 . 10 . 1171–8 . October 2010 . 20875357 . 10.1016/s1885-5857(10)70231-0.
  12. Sabatine MS, Morrow DA, Higgins LJ, MacGillivray C, Guo W, Bode C, Rifai N, Cannon CP, Gerszten RE, Lee RT . Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction . Circulation . 117 . 15 . 1936–44 . April 2008 . 18378613 . 10.1161/CIRCULATIONAHA.107.728022 . 4273564 .
  13. Boisot S, Beede J, Isakson S, Chiu A, Clopton P, Januzzi J, Maisel AS, Fitzgerald RL . Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure . J. Card. Fail. . 14 . 9 . 732–8 . November 2008 . 18995177 . 10.1016/j.cardfail.2008.06.415 .
  14. Web site: Critical Diagnostics . Critical Diagnostics .
  15. Web site: 510(k) Premarket Notification . United States Food and Drug Administration .

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