Diagnostic and prognostic value of growth differentiation factor 15 in suspected functionally relevant coronary artery disease
F Nafaa, G Hure, S Kul, K Durak, G Visconti, P Lopez Ayala, L Koechlin, J Boeddinghaus, L Crisanti, P Haaf, F Mahfoud, E Kaplan, M J Zellweger, I Strebel, C MuellerAbstract
Introduction
The rapid and accurate non-invasive diagnosis of significant and functionally relevant coronary artery disease (fCAD) is a crucial yet unmet clinical need. Growth differentiation factor 15 (GDF-15) may be involved in the development of CAD.
Purpose
We aimed to evaluate the diagnostic and prognostic value of GDF-15 in patients with suspected fCAD.
Methods
In this prospective cohort study, consecutive patients with suspected fCAD underwent myocardial perfusion imaging with single-photon-emission computed tomography, and coronary angiography plus fractional flow reserve, when available. The presence of fCAD was centrally adjudicated. GDF-15 concentrations were measured in a blinded fashion. Prognostic endpoints included all-cause mortality and cardiovascular death over five years.
Results
Among 3,379 patients eligible for this analysis (median age 68 years, 33% female, 44% known CAD), 1,160 patients (34%) had adjudicated fCAD. GDF-15 concentrations were significantly higher in patients with adjudicated fCAD compared to those without (1,325 ng/L (95%CI, 1,258-1,364) versus 1,041 ng/L (95%CI, 1,009-1,074), p<0.001). However, the diagnostic accuracy of GDF-15 for identifying fCAD was modest, with an area under the curve (AUC) of 0.598. When combined with clinical judgment, GDF-15 significantly increased the diagnostic accuracy (AUC 0.659). During a 5-year follow-up, 437 deaths (14%) occurred, of which 231 were cardiovascular. GDF-15 had very high prognostic accuracy for all-cause death and cardiovascular death (e.g. time-dependent AUC 0.815 and 0.834 at 2 years), at least comparable to high-sensitivity cardiac troponin (hs-cTn)T, and higher than hs-cTnI (Figures 1 and 2).
Conclusion
While GDF-15 has limited diagnostic utility, it exhibits high prognostic value in patients with suspected fCAD.