Abstract

Background: The impact of chronic kidney disease (CKD) on the association of cardiovascular (CV) and renal biomarkers with the presence and severity of coronary artery disease (CAD) in patients with suspected CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 2324 patients with suspected but no history of CAD undergoing elective coronary angiography, we assessed the impact of CKD on the association of CV and renal biomarkers with the presence and severity of CAD. Heparin-free fasting serum levels of soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), VEGF, placental growth factor (PlGF), N-terminal pro-brain natriuretic peptide (NT-proBNP), contemporary sensitive cardiac troponin-I (cTnI), high-sensitivity CRP (hs-CRP), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured in 887 CKD and 1437 non-CKD patients enrolled in the EXCEED-J study. The severity of CAD was quantified using the Gensini score. Results: The mean age (standard deviation) of the patients was 69.8 (10.8) years; 65.6% were men. Serum levels of all biomarkers except PlGF were significantly higher in CKD than in non-CKD patients. In the entire patient cohort, only natural log-transformed (Ln-) cTnI was significantly associated with CAD, multi-vessel or left main trunk disease (MVD/LMTD), and Ln-Gensini score after adjustment for potential confounders. These associations were still significant in non-CKD, but not in CKD: Ln-cTnI was significantly associated with MVD/LMTD and Ln-Gensini score, but not with CAD. Stepwise regression analyses including potential confounders and all biomarkers revealed that Ln-cTnI was independently associated with CAD, MVD/LMTD, and Ln-Gensini score in the entire cohort and in non-CKD, but not in CKD: Ln-cTnI was independently associated with MVD/LMTD and Ln-Gensini score, but not with CAD. No other biomarker exhibited an independent association with CAD, MVD/LMTD, or Ln-Gensini score in the entire cohort, in non-CKD, or in CKD. Conclusions: Among CV and renal biomarkers measured in this study, only Ln-cTnI was independently associated with the presence and severity of CAD in patients with suspected CAD. These associations were attenuated in patients with CKD.

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