Immunoassay for the in vitro quantitative determination of Growth Differentiation Factor‑15 (GDF‑15) in human serum and plasma
The Elecsys® GDF‑15 assay is intended as an aid in risk stratification of patients with Acute Coronary Syndrome (ACS) or Chronic Heart Failure (CHF) and as an aid in risk prediction of major bleeding events of patients with Atrial Fibrillation (AF). The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys® and cobas e immunoassay analyzers.
GDF‑15 is a member of the transforming growth factor β (TGF‑β) cytokine superfamily.
GDF‑15 levels increase sharply in response to pathological or physiological stress associated with inflammation, hypoxia, tissue injury and remodeling as observed in cardiovascular diseases, as well as in some tumors and pregnancy.1,2 Levels of GDF‑15 increase with the severity of cardiovascular diseases: elevated serum levels are found in stable coronary artery disease, ACS and heart failure (HF).2
Increasing evidence indicates that GDF‑15 levels predict adverse outcomes of cardiovascular disease, independently from traditional risk factors such as previous myocardial infarction (MI), age, elevated levels of cardiac troponin T, N‑terminal pro B‑type natriuretic peptide or high‑sensitivity C‑reactive protein. Increased GDF‑15 levels are indicative of high mortality in patients with ST-segment elevation ACS (STE‑ACS),3 non‑ST‑elevation ACS (NSTE‑ACS)4,5,6 and HF.7,8 Higher levels of GDF‑15 also identify NSTE‑ACS patients at an elevated risk of recurrent MI4 and bleeding.6
Adding GDF‑15 levels to the Global Registry of Acute Coronary Events (GRACE) score further improves the prediction of 6‑month all-cause mortality and non-fatal MI in patients with NSTE‑ACS.9
GDF‑15 levels may also assist in guiding therapeutic intervention: GDF‑15 levels in patients with NSTE‑ACS at admission predict those who are likely to benefit most from an early invasive versus non‑invasive treatment regime.4 High levels of GDF‑15 are also associated with increased risk of developing HF following an episode of ACS.10 Therefore GDF‑15 levels potentially allow identifying which ACS patients will benefit from more aggressive therapies aimed at reducing HF‑related admissions.
AF is highly associated with major risk for stroke and death. The development and risk of stroke can be mitigated by control of risk factors and oral anticoagulation therapy. However, anticoagulant therapy is strongly associated with a risk of major bleeding. Clinical practice points to the benefit of oral anticoagulation in AF on a balance between reduction in ischemic stroke and increase in major bleeding events. In clinical practice the risk of bleeding can be assessed by e.g. HAS‑BLED11 score and more recently by ORBIT12 score, which are based on clinical risk factors only. However, several new biomarkers have now been shown to provide incremental information about the risk of bleeding in AF patients. The recently introduced risk modelling score termed “ABC‑bleeding risk score” taking into account age, biomarkers (GDF‑15, cTNT‑hs, and hemoglobin) and clinical history was shown to significantly improve the prediction of bleeding events of AF patients.13 ABC-bleeding risk score could therefore be a valuable decision support tool regarding indications for and selection of treatment with oral anticoagulants in patients with AF.