Which Biomarkers Provide Prognostic Information on Mortality in Acute Coronary Syndrome?

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N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15 provide prognostic information in patients with ACS.

For patients with acute coronary syndrome, baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor-15 (GDF-15) are associated with all-cause death, particularly death resulting from heart failure, arrhythmia, and sudden cardiac death, according to results published in JAMA Cardiology.

Results were analyzed from study participants diagnosed with acute coronary syndrome enrolled in the Platelet Inhibition and Patient Outcomes trial from October 2006 through July 2008 (ClinicalTrials.gov identifier: NCT00391872). In the original study, 18,624 participants were randomly assigned to receive either ticagrelor or clopidogrel. In the secondary analysis performed to assess biomarkers, 17,095 participants were included.

The primary outcomes were death resulting from myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes, as well as all-cause death.

The researchers measured levels of cystatin-C, GDF-15, high-sensitivity C-reactive protein, high-sensitivity troponin I and T, and NT-proBNP at baseline.

During follow-up, 4.6% (n=782) of participants died.

The researchers found that NT-proBNP and GDF-15 were the strongest markers of all-cause mortality, with adjusted hazard ratios (HRs) of 2.96 (95% CI, 2.33-3.76) and 2.65 (95% CI, 2.17-3.24), respectively.

NT-proBNP was associated with an 8-fold increase in risk for death resulting from heart failure, whereas C-reactive protein, GDF-15, and cystatin-C were associated with a 3-fold increase in risk.

NT-proBNP was associated with a 4-fold increase in risk for death resulting from sudden cardiac death/arrhythmia, whereas GDF-15 was associated with a 2-fold increase in risk.

The researchers found that GDF-15 had the strongest association with other vascular and nonvascular deaths, with a potential association with death resulting from major bleeding (HR, 4.91; 95% CI, 1.39-17.43).

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“This could be potentially actionable information, whereby an estimated increased risk of death due to heart failure could instigate additional work-up, medical optimization and closer follow-up, as well as prevention of sudden cardiac death,” the researchers wrote.

Disclosures: This research was supported by AstraZeneca. Several study authors have disclosed potential conflicts of interest. Please refer to original manuscript for list of author disclosures.


Lindholm D, James SK, Gabrysch K, et al. Association of multiple biomarkers with risk of all-cause and cause-specific mortality after acute coronary syndromes: a secondary analysis of the PLATO biomarker study [published online November 14, 2018]. JAMA Cardiol. doi: 10.1001/jamacardio.2018.3811