Background and aims We investigated whether plasma cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) are associated with intravascular ultrasound (IVUS)-derived characteristics of coronary atherosclerosis and 1-year adverse coronary events in patients with normal and mildly-to-moderately impaired kidney function. Methods Between 2008 and 2011, virtual histology (VH)-IVUS of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography. Creatinine, CysC and NGAL were measured in pre-procedural blood samples. Presence of VH-IVUS-derived thin-cap fibroatheroma (TCFA) lesions, lesions with plaque burden (PB)≥70% and lesions with minimal luminal area (MLA)≤4 mm2 was assessed. Major adverse coronary events (MACE) comprised the composite of all-cause mortality, acute coronary syndrome, or unplanned coronary revascularization. Analyses were stratified using eGFRCr of 90 ml/min/1.73 m2 as the cut-off. Results In patients with normal kidney function, those with higher CysC levels had fewer lesions with PB ≥ 70% and fewer VH-TCFA lesions (adjusted odds ratios (ORs) and 95% confidence intervals (CIs): 0.46 [0.30–0.69] and 0.59 [0.44–0.83], respectively, per standard deviation (SD) ln[ng/mL] CysC). Those with higher NGAL levels also had fewer lesions with PB ≥ 70% (adjusted OR [95% CI]:0.49 [0.29–0.82]) In patients with impaired kidneys, no differences in high-risk lesions were observed for CysC or NGAL. However, those with higher CysC had higher risk of MACE (hazard ratio (HR):1.4, 95% CI [1.03–1.92]). This was not the case in patients with normal kidney function. NGAL did not influence risk of MACE. Conclusions: Mild-to-moderate kidney dysfunction modifies the relationship between CysC and high-risk coronary lesions. This has not been established before, and offers an explanation for the difference in findings between experimental and epidemiologic studies.

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Keywords Atherosclerosis, Cystatin C, Intravascular ultrasound, Kidney function, NGAL
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Journal Atherosclerosis
Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/201668 - European Collaborative Project on Inflamation and Vascular Wall Remodelling in Atherosclerosis (ATHEROREMO)
Brankovic, M, Akkerhuis, K.M, Buljubasic, N, Cheng, J.M, Oemrawsingh, R.M, Garcia-Garcia, H.M, … Kardys, I. (2016). Plasma cystatin C and neutrophil gelatinase-associated lipocalin in relation to coronary atherosclerosis on intravascular ultrasound and cardiovascular outcome. Atherosclerosis, 254, 20–27. doi:10.1016/j.atherosclerosis.2016.09.016