title: Multimarker Risk Stratification in Patients With Acute Myocardial Infarction.
abstract: Several biomarkers have individually been shown to be useful for risk stratification in patients with acute myocardial infarction (MI). The optimal multimarker strategy remains undefined.
  
  
  
  Biomarkers representing different pathobiological axes were studied, including myocardial stress/structural changes (NT-pro B-type natriuretic peptide [NT-proBNP], midregional proatrial natriuretic peptide [MR-proANP], suppression of tumorigenicity 2 [ST2], galectin-3, midregional proadrenomedullin [MR-proADM], and copeptin), myonecrosis (troponin T), and inflammation (myeloperoxidase [MPO], high sensitivity C-reactive protein [hsCRP], pregnancy-associated plasma protein A [PAPP-A], and growth-differentiation factor-15 [GDF-15]), in up to 1258 patients from Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28), a randomized trial of clopidogrel in ST-elevation MI (STEMI). Patients were followed for 30 days. Biomarker analyses were adjusted for traditional clinical variables. Forward step-wise selection was used to assess a multimarker strategy. After adjustment for clinical variables and using a dichotomous cutpoint, 7 biomarkers were each significantly associated with a higher odds of cardiovascular death or heart failure (HF) through 30 days, including NT-proBNP (adjusted odds ratio [ORadj], 2.54; 95% CI, 1.47-4.37), MR-proANP (2.18; 1.27-3.76), ST2 (2.88; 1.72-4.81), troponin T (4.13; 1.85-9.20), MPO (2.75; 1.20-6.27), hsCRP (1.96, 1.17-3.30), and PAPP-A (3.04; 1.17-7.88). In a multimarker model, 3 biomarkers emerged as significant and complementary predictors of cardiovascular death or HF: ST2 (ORadj, 2.87; 1.61-5.12), troponin T (2.34; 1.09-5.01 and 4.13, 1.85-9.20, respectively for intermediate and high levels), and MPO (2.49; 1.04-5.96). When added to the TIMI STEMI Risk Score alone, the multimarker risk score significantly improved the C-statistic (area under the curve, 0.75 [95% CI, 0.69-0.81] to 0.82 [0.78-0.87]; P=0.001), net reclassification index (0.93; P<0.001), and integrated discrimination index (0.09; P<0.001).
  
  
  
  In patients with STEMI, a multimarker strategy that combines biomarkers across pathobiological axes of myocardial stress, myocyte necrosis, and inflammation provides incremental prognostic information for prediction of cardiovascular death or HF.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA modonoghue@partners.org.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: O'Donoghue
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: Petr
authors.initials: P
authors.lastname: Jarolim
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Desai
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Sherwood
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: Cardiolovascular Division, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D053607:Adrenomedullin / Q000097:blood; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001798:Blood Proteins; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism / Q000401:mortality; D005260:Female; D037502:Galectin 3 / Q000097:blood; D037161:Galectins; D006020:Glycopeptides / Q000097:blood; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood; D009195:Peroxidase / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood; D018570:Risk Assessment; D000072657:ST Elevation Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; C526140:GDF15 protein, human; D037502:Galectin 3; D037161:Galectins; D006020:Glycopeptides; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; C428445:LGALS3 protein, human; D010446:Peptide Fragments; D011498:Protein Precursors; D020107:Troponin T; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; C552580:midregional pro-atrial natriuretic peptide, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein; D009195:Peroxidase; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: ST‐elevation myocardial infarction; Thrombolysis in Myocardial Infarction risk score; biomarkers; multimarker; prognosis