Dataset Information

Multimarker Risk Stratification in Patients With Acute Myocardial Infarction.

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.

SUBMITTER: O'Donoghue ML

PROVIDER: S-EPMC4889163 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Multimarker Risk Stratification in Patients With Acute Myocardial Infarction.

O'Donoghue Michelle L ML Morrow David A DA Cannon Christopher P CP Jarolim Petr P Desai Nihar R NR Sherwood Matthew W MW Murphy Sabina A SA Gerszten Robert E RE Sabatine Marc S MS

Journal of the American Heart Association 20160520 5

<h4>Background</h4>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.<h4>Methods and results</h4>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 ...[more]

PMID: 27207959

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Project description:BackgroundDespite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction.ObjectivesThe goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction.MethodsThe T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe.ResultsThere were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts.ConclusionsThe T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome [High-STEACS]; NCT01852123).

Project description:BackgroundMany mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice.Methods and findingsWe developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/μL, <10 g/dL, >1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened in-hospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the in-hospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II substudy; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01).ConclusionsThis laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index.

Project description:BackgroundStrain analyses derived from cardiovascular magnetic resonance-feature tracking (CMR-FT) provide incremental prognostic benefit in patients sufferring from acute myocardial infarction (AMI). This study aims to evaluate and revalidate previously reported prognostic implications of comprehensive strain analyses in a large independent cohort of patients with ST-elevation myocardial infarction (STEMI).MethodsOverall, 566 STEMI patients enrolled in the CONDITIONING-LIPSIA trial including pre- and/or postconditioning treatment in addition to conventional percutaneous coronary intervention underwent CMR imaging in median 3 days after primary percutaneous coronary intervention. CMR-based left atrial (LA) reservoir (Es), conduit (Ee), and boosterpump (Ea) strain analyses, as well as left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) analyses were carried out. Previously identified cutoff values were revalidated for risk stratification. Major adverse cardiac events (MACE) comprising death, reinfarction, and new congestive heart failure were assessed within 12 months after the occurrence of the index event.ResultsBoth atrial and ventricular strain values were significantly reduced in patients with MACE (p < 0.01 for all). Predetermined LA and LV strain cutoffs enabled accurate risk assessment. All LA and LV strain values were associated with MACE on univariable regression modeling (p < 0.001 for all), with LA Es emerging as an independent predictor of MACE on multivariable regression modeling (HR 0.92, p = 0.033). Furthermore, LA Es provided an incremental prognostic value above LVEF (a c-index increase from 0.7 to 0.74, p = 0.03).ConclusionExternal validation of CMR-FT-derived LA and LV strain evaluations confirmed the prognostic value of cardiac deformation assessment in STEMI patients. In the present study, LA strain parameters especially enabled further risk stratification and prognostic assessment over and above clinically established risk parameters.Clinical trial registrationClinicalTrials.gov, identifier NCT02158468.

Dataset Information

Multimarker Risk Stratification in Patients With Acute Myocardial Infarction.

Background

Methods and results

Conclusions

Publications

Multimarker Risk Stratification in Patients With Acute Myocardial Infarction.

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