Plasma cystatin C and neutrophil gelatinase-associated lipocalin in relation to coronary atherosclerosis on intravascular ultrasound and cardiovascular outcome: Impact of kidney function (ATHEROREMO-IVUS study)

Abstract

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 eGFR_Cr 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.

Keywords: Atherosclerosis; Cystatin C; Intravascular ultrasound; Kidney function; NGAL.