Incremental Prognostic Value of Biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) Score and High-Sensitivity Cardiac Troponin T in Non-ST-Elevation Acute Coronary Syndrome

Abstract

BACKGROUND Guidelines recommend the use of validated risk scores and a high-sensitivity cardiac troponin assay for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). The incremental prognostic value of biomarkers in this context is unknown. METHODS We calculated the Global Registry of Acute Coronary Events (GRACE) score and measured the circulating concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and 8 selected cardiac biomarkers on admission in 1146 patients with NSTE-ACS. We used an hs-cTnT threshold at the 99th percentile of a reference population to define increased cardiac marker in the score. The magnitude of the increase in model performance when individual biomarkers were added to GRACE was assessed by the change (Δ) in the area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), and category-free net reclassification improvement [NRI(>0)]. RESULTS Seventy-eight patients reached the combined end point of 6-month all-cause mortality or nonfatal myocardial infarction. The GRACE score alone had an AUC of 0.749. All biomarkers were associated with the risk of the combined end point and offered statistically significant improvement in model performance when added to GRACE (likelihood ratio test P ≤ 0.015). Growth differentiation factor 15 [ΔAUC 0.039, IDI 0.049, NRI(>0) 0.554] and N-terminal pro–B-type natriuretic peptide [ΔAUC 0.024, IDI 0.027, NRI(>0) 0.438] emerged as the 2 most promising biomarkers. Improvements in model performance upon addition of a second biomarker were small in magnitude. CONCLUSIONS Biomarkers can add prognostic information to the GRACE score even in the current era of high-sensitivity cardiac troponin assays. The incremental information offered by individual biomarkers varies considerably, however.

Targeted multiple biomarker approach in predicting cardiovascular events in patients with diabetes

“…GDF-15 predicts cardiovascular events in patients with acute coronary syndrome and heart failure and in elderly individuals 8 11. Moreover, head-to-head comparisons with NT-proBNP reveal independent strong and incremental prognostic value of GDF-15 in patients with non-ST-elevation acute coronary syndrome12 and advanced heart failure 13. Interestingly, GDF-15 concentrations strongly correlate with insulin resistance and are increased in patients with diabetes when compared with age-matched and gender-matched control subjects 14 15.…”

Long-term prognostic utility of pentraxin 3 and D-dimer as compared to high-sensitivity C-reactive protein and B-type natriuretic peptide in suspected acute coronary syndrome

“…Increased levels of hsCRP have been associated with worsened outcomes in all stages of both stable and unstable CAD [16][17][18][19] , but more recent data, however, might suggest a less important role of hsCRP in the evaluation of ACS patients, 3,20 questioning its incremental, prognostic value in non-ST elevation ACS patients. 21,22 In addition, results from recent studies on chest pain patients are conflicting.…”

Czynnik różnicowania wzrostu 15 jako biomarker w niewydolności serca

“…Dodanie GDF-15 do skali ryzyka GRACE (Global Registry Of Acute Cardiac Events) poprawiało stratyfikację ryzyka (wystąpie-nia) zgonu i ponownego zawału niezakończonego zgonem [4]. W innej pracy GDF-15 okazał się także istotnym czynnikiem predykcyjnym zgonu i pozawałowej HF u chorych z przebytym zawałem serca [7].…”