Multimarker Risk Stratification in Patients With Acute Myocardial Infarction

Background: 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. methods and results: 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). conclusions: 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. © 2016 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.