Limitations of NLR×GDF-15 as a Predictor of Major Adverse Events after CABG: Methodological Concerns

Recent studies have examined the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and growth differentiation factor-15 (GDF-15), used alone or in combination, for predicting major adverse cardiovascular events (MACE) after coronary artery bypass grafting (CABG). The authors concluded that NLR×GDF-15 has moderate prognostic ability. Although the idea of combining biomarkers is attractive, we highlight its significant limitations: small sample size, lack of validation and calibration, arbitrary transformation of biomarkers, short follow-up period, heterogeneous endpoint definitions, lack of comparison with established risk scores, and the confounding effect of renal function. Current methodological standards (TRIPOD+AI, PROBAST+AI) emphasize the importance of rigorous validation and transparency. Until larger multicenter studies confirm these findings, NLR×GDF-15 should not be considered a reliable prognostic marker in CABG patients.