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 [OR (adj)], 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 (OR (adj), 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.