Growth-Differentiation Factor-15 in the Early Diagnosis and Risk Stratification of Patients With Acute Chest Pain

Study Questions:

Can growth-differentiation factor-15 (GDF-15), a stress-responsive marker, aid in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI)?

Methods:

The authors measured GDF-15, high-sensitivity cardiac troponin T (hs-cTnT), and B-type natriuretic peptide (BNP) in a prospective, international, multicenter study, in 646 unselected patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists. The primary prognostic endpoint was all-cause mortality during a median follow-up of 26 months.

Results:

AMI was the final diagnosis in 115 patients (18%). GDF-15 concentrations at presentation were significantly higher in AMI patients compared to patients with other diagnoses. The diagnostic accuracy of GDF-15 at presentation for the diagnosis of AMI, as quantified by the area under the receiver operating characteristic curve (AUC) was lower (AUC 0.69; 95% confidence interval [CI], 0.64-0.74) compared to hs-cTnT (AUC 0.96; 95% CI, 0.94-0.98; p < 0.001) and BNP (AUC 0.74; 95% CI, 0.69-0.80; p = 0.02). A total of 55 deaths occurred during follow-up. GDF-15 predicted all-cause mortality independently of and more accurately than hs-cTnT (AUC 0.85; 95% CI, 0.81-0.90 vs. AUC 0.77; 95% CI, 0.72-0.83; p = 0.002) and BNP (AUC 0.75; 95% CI, 0.68-0.82; p = 0.007). Net reclassification improvement was 0.15 (p = 0.01), and the absolute integrated discrimination improvement was 0.07, yielding a relative integrated discrimination improvement of 0.36 (p = 0.07).

Conclusions:

The authors concluded that GDF-15 predicts all-cause mortality in unselected patients with acute chest pain independently of and more accurately than hs-cTnT and BNP. However, GDF-15 was not useful for the early diagnosis of AMI.

Perspective:

Those enamored with the use of what are loosely called ‘death markers’ (ST2, proADM, and GDF-15) will find support in this paper, which compares BNP, hs-cTnT, and GDF-15 as predictors of mortality after presentation with acute coronary syndrome. Those who are not enamored with so-called ‘death markers’ may find this paper a bit of a stretch. GDF-15 was not highly efficacious as a diagnostic marker for AMI, but was equivalent to BNP as a predictor of death. However, none of the markers were highly predictive of cardiovascular death after multivariate modeling, suggesting that some of the impact of GDF-15, a marker also increased in patients with abnormal insulin metabolism, may be more helpful in the absence than the presence of cardiovascular disease. Of interest, ejection fraction was not available in all the members of this cohort, so it was not included in the modeling. It may have helped in cardiovascular prediction.

Clinical Topics: Acute Coronary Syndromes, ACS and Cardiac Biomarkers

Keywords: Risk, Acute Coronary Syndrome, Myocardial Infarction, Follow-Up Studies, Early Diagnosis, Prognosis, Cytoskeletal Proteins, Biological Markers, Chest Pain, Cardiology, Growth Differentiation Factor 15, Cardiovascular Diseases


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