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
Introduction and methods
Background
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.
Methods
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).
Outcome
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).
Conclusion
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.”
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