Prognostic value of repeated biomarker sampling post-ACS

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort

Literature - Gürgöze MT, Akkerhuis KM, Oemrawsingh RM, et al. - Eur Heart J Acute Cardiovasc Care. 2023 Apr 25;zuad042 [Online ahead of print]. doi: 10.1093/ehjacc/zuad042

Introduction and methods


For prognostication in ACS, several promising markers have emerged, such as NT-proBNP [1,2], CRP [1,3], and growth differentiation factor 15 (GDF-15) [4]. However, most findings are based on a single measurement at baseline, which did not take into account the dynamics during follow-up and across the clinical disease spectrum.

Aim of the study

The study aim was to explore the prognostic value of 4 serially measured biomarkers (i.e., hs-cTnT, NT-proBNP, hs-CRP, and GDF-15) in a large, real-world cohort of post-ACS patients.


The BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) study is a Dutch, prospective, multicenter, observational study in 844 patients aged >40 years who were hospitalized for ACS (including STEMI, NSTEMI, and unstable angina) with ≥1 additional CV risk factor. During 1 year after the index admission for ACS, patients underwent highly frequent blood sampling (total number of samples: 12,218; median number of samples per patient: 17; IQR: 12–20). The first sample during the acute phase was taken at a median time of 14 days (IQR: 2–31).


The primary endpoint was a composite outcome of CV death or recurrent nonfatal ACS event, including MI or recurrent unstable angina requiring urgent coronary revascularization, during 1-year follow-up.

Main results

Longitudinal evolution of biomarker levels

  • In patients who reached the primary endpoint (n=45), mean levels at first sample of NT-proBNP (P=0.006) and GDF-15 (P<0.001) were higher compared with those in the other 799 patients. There were no differences in mean hs-cTnT and hs-CRP levels at first sample.
  • Mean baseline GRACE (Global Registry of Acute Coronary Events) score was higher in patients who met the primary endpoint compared with those who did not (121 vs. 94; P<0.001), and a larger proportion of the first group was categorized as “high GRACE risk” (51% vs. 19%; P<0.001).
  • During follow-up, mean biomarker levels were higher in patients who met the primary endpoint compared with event-free patients. There was no clear divergent time-to-event pattern in biomarker levels between the groups, except for GDF-15, which showed a significant steady increase prior to the occurrence of the primary endpoint, while its level remained considerably stable in event-free patients.

Association of serially measured biomarker level with prognosis

  • Occurrence of the primary endpoint was associated with 1-SD increase in the level (on log-scale) of hs-cTnT (HR: 2.09; 95%CI: 1.43–2.90; P<0.001), NT-proBNP (HR: 2.04; 95%CI: 1.35–2.08; P<0.001), hs-CRP (HR: 1.72; 95%CI: 1.04–2.79; P=0.039), and GDF-15 (HR: 2.24; 95%CI: 1.62–3.04; P<0.001).
  • After adjustment for GRACE score, these associations remained significant for hs-cTnT (HR: 1.61; 95%CI: 1.02–2.44; P=0.045) and GDF-15 (HR: 1.81; 95%CI: 1.28–2.70; P=0.001) but not for NT-proBNP or hs-CRP.
  • In multimarker models, hs-cTnT and GDF-15 remained strong independent prognostic factors (all P≤0.012), except when hs-cTnT was adjusted for GDF-15 (P=0.070).


This analysis of the BIOMArCS study showed that longitudinal levels of hs-cTnT and GDF-15, but not NT-proBNP and hs-CRP, were strong independent prognostic factors of the primary endpoint (i.e., CV death or recurrent nonfatal ACS event) in clinically stabilized post-ACS patients during 1-year follow-up. Prior to the occurrence of the primary endpoint, the GDF-15 level increased steadily, while there appeared to be no prominent divergence in hs-cTnT, NT-proBNP, and hs-CRP levels. The authors therefore concluded that “serial measurements seem most promising for GDF-15 to provide early insight into an upcoming event.”


1. Kim H, Yang DH, Park Y, Han J, Lee H, Kang H, et al. Incremental prognostic value of C-reactive protein and N-terminal proB-type natriuretic peptide in acute coronary syndrome. Circ J. 2006;70:1379–1384.

2. Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM, et al. Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. J Am Coll Cardiol. 2003;41:1264–1272.

3. Sabatine MS, Morrow DA, de Lemos JA, Gibson CM, Murphy SA, Rifai N, et al. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation. 2002;105:1760–1763.

4. Wollert KC, Kempf T, Peter T, Olofsson S, James S, Johnston N, et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome. Circulation. 2007;115:962–971.

Find this article online at Eur Heart J Acute Cardiovasc Care.

Facebook Comments


We’re glad to see you’re enjoying PACE-CME…
but how about a more personalized experience?

Register for free