title: Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction.
abstract: BACKGROUND
  ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established.
  
  
  RESULTS
  We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017).
  
  
  CONCLUSIONS
  In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST-elevation myocardial infarction.
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. msabatine@partners.org
authors: Marc S
authors: MS
authors: Sabatine
authors: David A
authors: DA
authors: Morrow
authors: Luke J
authors: LJ
authors: Higgins
authors: Catherine
authors: C
authors: MacGillivray
authors: Wei
authors: W
authors: Guo
authors: Christophe
authors: C
authors: Bode
authors: Nader
authors: N
authors: Rifai
authors: Christopher P
authors: CP
authors: Cannon
authors: Robert E
authors: RE
authors: Gerszten
authors: Richard T
authors: RT
authors: Lee
mesh_terms: D000368:Aged; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000401:mortality; D015897:Comorbidity; D017023:Coronary Angiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011956:Receptors, Cell Surface / Q000097:blood*; D013314:Stress, Mechanical; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain