Clinical criteria replenish high-sensitive troponin and inflammatory markers in the stratification of patients with suspected acute coronary syndrome

OBJECTIVES: In patients with suspected acute coronary syndrome (ACS), rapid triage is essential. The aim of this study was to establish a tool for risk prediction of 30-day cardiac events (CE) on admission. 30-day cardiac events (CE) were defined as early coronary revascularization, subsequent myocardial infarction, or cardiovascular death within 30 days. METHODS AND RESULTS: This single-centre, prospective cohort study included 377 consecutive patients presenting to the emergency department with suspected ACS and for whom troponin T measurements were requested on clinical grounds. Fifteen biomarkers were analyzed in the admission sample, and clinical parameters were assessed by the TIMI risk score for unstable angina/Non-ST myocardial infarction and the GRACE risk score. Sixty-nine (18%) patients presented with and 308 (82%) without ST-elevations, respectively. Coronary angiography was performed in 165 (44%) patients with subsequent percutaneous coronary intervention - accounting for the majority of CE - in 123 (33%) patients, respectively. Eleven out of 15 biomarkers were elevated in patients with CE compared to those without. High-sensitive troponin T (hs-cTnT) was the best univariate biomarker to predict CE in Non-ST-elevation patients (AUC 0.80), but did not yield incremental information above clinical TIMI risk score (AUC 0.80 vs 0.82, p = 0.69). Equivalence testing of AUCs of risk models and non-inferiority testing demonstrated that the clinical TIMI risk score alone was non-inferior to its combination with hs-cTnT in predicting CE. CONCLUSIONS: In patients presenting without ST-elevations, identification of those prone to CE is best based on clinical assessment based on TIMI risk score criteria and hs-cTnT

Diagnostic performance of high-sensitive cardiac troponin T (hs-cTnT), myeloperoxidase (MPO), myeloid-related protein 8/14 (MRP 8/14), and conventional cardiac troponin T (c-cTnT) in relation to the clinical TIMI risk score of patients with suspected ACS and no obvious ST-segment elevations at presentation (Non-ST-elevation patients).

<p>AUC indicates area under the curve. The clinical TIMI risk score is the sum of 6 clinical factors without the biomarker variable of the 7 originally described risk predictors of the TIMI unstable angina/Non-ST myocardial infarction risk score.</p

Baseline characteristics.

<p>Abbreviations: CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting, PVD, peripheral vascular disease; CVD, cerebrovascular disease; ACE, angiotensin converting enzyme; CCB, calcium channel blocker; BMI, body mass index.</p

Study flow chart of the prospective, observational MyRiAD study.

<p>Abbreviations: ER, emergency room; CA, coronary angiography; CAD, coronary artery disease; CE, cardiac events (composite of early coronary revascularization by percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG], subsequent myocardial infarction or cardiovascular death); c-cTnT, conventional cardiac troponin T; CK, creatine kinase; CK-MB, creatine kinase-myocardial band.</p

Biomarker levels in patients with and without cardiac events (CE).

<p>Abbreviations: CK, creatine kinase; CK-MB, creatine kinase-myocardial band; H-FABP, heart-type fatty acid-binding protein; c-cTnT, conventional cardiac troponin T; hs-cTnT, high-sensitive cardiac troponin T; NT-proBNP, N-terminal pro-brain natriuretic peptide; hs-CRP, high-sensitive C-reactive protein; Il-6, interleukin-6; MPO, myeloperoxidase; MRP 8/14, myeloid-related protein 8/14; PAPP-A, pregnancy-associated protein A; IGF-1, insulin-like growth factor 1.</p

Predictiveness curves illustrating the prognostic performance of two different risk models in predicting cardiac events (CE).

<p>Risk model I: clinical TIMI risk score and gender; Risk model II: clinical TIMI risk score, gender, and hs-cTnT, respectively.</p

Final diagnoses.

<p>Abbreviations: CAD, coronary artery disease; NSTEMI, non-ST-elevation myocardial infarction; UA, unstable angina.</p

Multivariate classification tree analysis of clinical and multiple biomarker information and the resulting algorithm for the identification of those at risk of cardiac events (CE) within 30 days among patients presenting with suspected ACS and no apparent ST-segment elevations (Non-ST-elevation patients).

<p>No significant classification with regard to 30-day CE was possible using the clinical GRACE risk score (Bonferroni-adjusted p-value = 0.368).</p

Multivariate classification tree analysis of clinical and multiple biomarker information and the resulting algorithm for the identification of those at risk of cardiac events (CE) within 30 days among patients presenting with suspected ACS and no apparent ST-segment elevations (Non-ST-elevation patients).

<p>Hs-cTnT indicates high-sensitive cardiac troponin T (pg/mL), no-CE denotes patients free from cardiac events (CE) within 30 days. The clinical TIMI score is the sum of 6 clinical factors without the biomarker variable of the 7 originally described risk predictors of the TIMI unstable angina/Non-ST myocardial infarction risk score.</p

ROC-analysis for cardiac events (CE) at 30 days.

<p>Abbreviations: AUC, area under the curve; SE, standard error; CI, confidence intervall; PPV, positive predictive value; NPV, negative predictive value; hs-cTnT, high-sensitive cardiac troponin T; c-cTnT, conventional cardiac troponin T; H-FABP, heart-type fatty acid-binding protein; MRP 8/14, myeloid-related protein 8/14; PAPP-A, pregnancy-associated protein A; MPO, myeloperoxidase; CK-MB, creatine kinase-myocardial band; CK, creatine kinase; hs-CRP, high-sensitive C-reactive protein; NT-proBNP, N-terminal pro-brain natriuretic peptide; IL-6, interleukin-6; and IGF-1, insulin-like growth factor 1. The clinical TIMI risk score is the sum of 6 clinical factors without the biomarker variable of the 7 originally described risk predictors of the TIMI unstable angina/Non-ST myocardial infarction risk score.</p