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.