Growth Differentiation Factor 15 Is Associated with Severe Coronary Artery Calcification in Patients with Chronic Kidney Disease

Abstract

Patients with chronic kidney disease (CKD) have a high burden of coronary artery calcification (CAC) and cardiovascular risk. GDF-15 is a stress-responsive biomarker linked to kidney dysfunction and adverse cardiovascular outcomes, but its relationship with CAC across CKD stages is incompletely characterized. We evaluated associations of GDF-15 with severe CAC and major adverse cardiovascular events (MACE). In this prospective observational study, 128 patients with CKD and no previous cardiovascular disease had baseline GDF-15, dp-ucMGP, high-sensitivity cardiac troponin I, and NT-proBNP measured; CAC was quantified by computed tomography in 127. Severe CAC was defined as Agatston score ≥ 400. Mean serum GDF-15 was 4.5 ± 3.4 ng/mL. GDF-15 discriminated severe CAC (AUC 0.728; 95% CI 0.642–0.804; p < 0.001). Each doubling of GDF-15 was associated with higher odds of severe CAC after adjustment for eGFR, diabetes, LDL cholesterol, and phosphate (OR 2.105; 95% CI 1.045–4.240; p = 0.037), but this association was attenuated after adding high-sensitivity troponin I (p = 0.086). During 19 months, nine MACE occurred; each doubling of GDF-15 was associated with higher MACE risk (HR 2.679; 95% CI 1.278–5.625; p = 0.009). Higher GDF-15 was associated with severe CAC and cardiovascular events, supporting further evaluation in CKD.