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Multiple biomarkers and cause-specific mortality in patients with acute coronary syndromes - Insights from the PLATO biomarker substudy

Session Poster Session 1

Speaker Daniel Lindholm

Congress : ESC Congress 2018

  • Topic : coronary artery disease, acute coronary syndromes, acute cardiac care
  • Sub-topic : Acute Coronary Syndromes: Biomarkers
  • Session type : Poster Session
  • FP Number : P823

Authors : D Lindholm (Uppsala,SE), S James (Uppsala,SE), K Gabrysch (Uppsala,SE), RF Storey (Sheffield,GB), A Himmelmann (Gothenburg,SE), CP Cannon (Boston,US), KW Mahaffey (Stanford,US), PG Steg (Paris,FR), C Held (Uppsala,SE), A Siegbahn (Uppsala,SE), L Wallentin (Uppsala,SE)


D. Lindholm1 , S. James1 , K. Gabrysch1 , R.F. Storey2 , A. Himmelmann3 , C.P. Cannon4 , K.W. Mahaffey5 , P.G. Steg6 , C. Held1 , A. Siegbahn7 , L. Wallentin1 , 1Uppsala Clinical Research Center - Uppsala - Sweden , 2University of Sheffield - Sheffield - United Kingdom , 3AstraZeneca Research and Development - Gothenburg - Sweden , 4Brigham and Women's Hospital - Boston - United States of America , 5Stanford University, Stanford Center for Clinical Research - Stanford - United States of America , 6University Paris Diderot - Paris - France , 7Uppsala University - Uppsala - Sweden ,

On behalf: PLATO investigators

European Heart Journal ( 2018 ) 39 ( Supplement ), 145-146

Background: In patients with acute coronary syndrome (ACS), there is still a residual mortality at about 5% within a year despite early invasive procedures, dual antiplatelet treatment and other secondary preventive measures. Identifying specific predictors of causes of death during aggressive secondary prevention might enable additional preemptive treatment. We therefore assessed the associations between multiple biomarkers and cause-specific mortality.

Methods: We included 17905 ACS patients who participated in the biomarker substudy of the Platelet inhibition and patient outcomes (PLATO) study (NCT00391872). Troponin (Tn) I and T (high sensitivity assays), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), Cystatin-C and Growth-differentiation factor 15 (GDF-15) were measured in samples obtained at entry. The associations between biomarkers and cause-specific mortality were modeled using Cox proportional hazards models adjusted for clinical characteristics.

Results: The causes of death of the 4.7% patients who died during follow-up were: myocardial infarction (MI) 1.9%, sudden death 0.9%, heart failure (HF) 0.4%, bleeding 0.1%, and the remainder from other causes. The top marker for death from MI was GDF-15 followed by NT-proBNP and TnT. For sudden cardiac death and HF, NT-proBNP was by far the strongest predictor followed by CRP for heart failure, and GDF-15 for sudden cardiac death. The only marker showing a trend towards association with death from bleeding was GDF-15.

Conclusion: In patients with ACS treated in accordance with current guidelines a raised risk of cause-specific death is indicated by a higher level of different biomarkers. The risk for fatal re-infarction is best predicted by GDF-15, NT-proBNP and TnT, and sudden cardiac death by NT-proBNP and GDF-15. The risk for death from HF is best predicted by NT-proBNP, CRP and GDF-15, while fatal bleeding could possibly be predicted by GDF-15.

Table 1. Causes of death in relation to upper vs. lower biomarker quartile
All-cause death (4.7%)Death from MI (1.9%)Sudden cardiac death/ Arrhythmia (0.9%)Death from HF (0.4%)Death from bleeding (0.1%)
HR (95% CI)HR (95% CI)HR (95% CI)HR (95% CI)HR (95% CI)
CRP1.73 (1.42–2.10)1.61 (1.18–2.20)1.52 (0.98–2.35)3.61 (1.70–7.68)1.09 (0.36–3.26)
Cystatin C1.70 (1.40–2.07)1.58 (1.17–2.13)1.36 (0.89–2.08)3.07 (1.43–6.62)1.77 (0.58–5.43)
GDF-152.65 (2.17–3.24)2.79 (2.04–3.81)2.02 (1.31–3.11)3.16 (1.46–6.85)4.91 (1.39–17.43)
hs-Troponin I1.24 (1.01–1.52)1.85 (1.32–2.61)0.60 (0.38–0.95)1.59 (0.74–3.44)0.83 (0.26–2.62)
hs-Troponin T1.56 (1.27–1.92)2.24 (1.59–3.15)0.72 (0.46–1.14)1.68 (0.79–3.57)1.14 (0.35–3.66)
NT-proBNP2.96 (2.33–3.76)2.74 (1.89–3.98)3.89 (2.29–6.60)8.20 (2.60–25.88)1.43 (0.43–4.75)

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