May 6, 2016Journal of the American Heart Association139 citationsOpen Access
View Full PaperMultimarker Risk Stratification in Patients With Acute Myocardial Infarction
Key Result
A multimarker risk score adding ST2, troponin T, and MPO to the TIMI STEMI Risk Score improved the C-statistic for 30-day cardiovascular death or heart failure from 0.75 to 0.82 (P=0.001).
Study Design
Type
Cohort (n=1,258)
PICO
P
Population
1,258 patients with ST-elevation myocardial infarction from the CLARITY-TIMI 28 trial, followed for 30 days.
E
Exposure / Comparator
Multimarker risk score (ST2, troponin T, and MPO) vs TIMI STEMI Risk Score alone
O
Primary Outcome
Cardiovascular death or heart failure (HF) through 30 days — C-statistic 0.82 (0.78-0.87), p=0.001
Main Result
Effect estimate: C-statistic 0.82 (95% CI 0.78-0.87)
p-value: p=0.001
Abstract
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.
Cite This Study
O’Donoghue et al. (Fri,) conducted a cohort in ST-elevation myocardial infarction (STEMI) (n=1,258). Multimarker risk score (ST2, troponin T, and MPO) vs. TIMI STEMI Risk Score alone was evaluated on Cardiovascular death or heart failure (HF) through 30 days (C-statistic 0.82, 95% CI 0.78-0.87, p=0.001). A multimarker risk score adding ST2, troponin T, and MPO to the TIMI STEMI Risk Score improved the C-statistic for 30-day cardiovascular death or heart failure from 0.75 to 0.82 (P=0.001).