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).
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.



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 mm2was assessed. Major adverse coronary events (MACE) comprised the composite of all-cause mortality, acute coronary syndrome, or unplanned coronary revascularization. Analyses were stratified using eGFRCrof 90 ml/min/1.73 m2as the cut-off.



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.



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.
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Milos
M
Brankovic
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
K Martijn
KM
Akkerhuis
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Nermina
N
Buljubasic
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Jin M
JM
Cheng
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands; Netherlands Heart Institute, Utrecht, The Netherlands.
Rohit M
RM
Oemrawsingh
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Hector M
HM
Garcia-Garcia
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Evelyn
E
Regar
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Patrick W
PW
Serruys
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Robert-Jan
RJ
van Geuns
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Eric
E
Boersma
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands. Electronic address: i.kardys@erasmusmc.nl.
Isabella
I
Kardys
D054058:Acute Coronary Syndrome / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood*; D003331:Coronary Vessels / Q000473:pathology; D055316:Cystatin C / Q000097:blood*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000502:physiology; D007677:Kidney Function Tests; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011446:Prospective Studies; D018084:Ultrasonography, Interventional
D015415:Biomarkers; D055316:Cystatin C; D000071068:Lipocalin-2
Atherosclerosis; Cystatin C; Intravascular ultrasound; Kidney function; NGAL