Chronic kidney disease predicts coronary plaque vulnerability: an optical coherence tomography study Jiannan Dai a,b , Lei Xing a,b , Jingbo Hou a , Haibo Jia a , Sining Hu a , Jinwei Tian a , Lin Lin a , Lulu Li a , Yinchun Zhu a , Gonghui Zheng a , Shaosong Zhang a , Bo Yu a and Ik-Kyung Jang b Objective The addition of cystatin C to creatinine in calculating the estimated glomerular filtration rate (eGFR) is known to improve the risk prediction for cardiovascular events. We sought to investigate the associations between eGFRs calculated by three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and coronary plaque phenotype by optical coherence tomography. Patients and methods We analyzed 181 nonculprit plaques from 116 coronary artery disease patients. For each patient, the eGFR was calculated using the CKD- EPI creatinine , CKD-EPI cystatin C , and CKD-EPI combination equations. Patients were divided into three categories according to the eGFR calculated by each equation (≥90, 60–89, and < 60 ml/min/1.73 m 2 ). Results The prevalence of thin-cap fibroatheroma (TCFA) was correlated inversely with eGFR calculated using CKD- EPI cystatin C and CKD-EPI combination equations, but not using the CKD-EPI creatinine equation. The best cut-off values of eGFR calculated by these two equations for differentiating TCFA were 83 and 84 ml/min/1.73 m 2 , respectively. Compared with the CKD-EPI creatinine equation, patients who were reclassified upward or downward categories by the CKD-EPI cystatin C equation were associated with consistently lower [adjusted odds ratio = 0.27, 95% confidence interval (CI), 0.08–0.86] and higher (adjusted odds ratio = 2.41, 95% CI, 1.08–5.41) prevalence for TCFA, respectively. The net reclassification improvement with cystatin C, compared with creatinine, was 0.45 (95% CI, 0.20–0.69) for TCFA, 0.38 (95% CI, 0.09–0.67) for thrombus, and 0.21 (95% CI, 0.00–0.42) for cholesterol crystals. Results were generally similar for the CKD-EPI combination equation. Conclusion The use of cystatin C alone or in combination with creatinine, compared with creatinine alone, for GFR estimation strengthens the associations between the eGFR and prevalence of vulnerable plaque characteristics. Coron Artery Dis 28:135–144 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. Coronary Artery Disease 2017, 28:135–144 Keywords: cystatin C, estimated glomerular filtration rate, optical coherence tomography, plaque vulnerability a Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China and b Massachusetts General Hospital, Harvard Medical School, Cardiology Division, Boston, Massachusetts, USA Correspondence to Bo Yu, MD, PhD, FACC, Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, 246 Xuefu Road, Nangang District, Harbin 150086, China Tel: + 86 451 866 05359; fax: + 86 451 866 05180; e-mail: yubodr@163.com Received 6 October 2016 Revised 15 October 2016 Accepted 24 October 2016 Introduction Renal insufficiency is an independent risk factor for adverse cardiovascular events, even in patients with mild to moderate kidney dysfunction [1]. Pathology study has shown that a lower estimated glomerular filtration rate (eGFR) is associated with the severity of coronary atherosclerosis and calcification [2]. However, the rela- tionship between creatinine-based eGFR and coronary plaque vulnerability in vivo is still controversial. Several intravascular ultrasound (IVUS) studies have suggested that there are no differences in the extent or the pro- gression of atherosclerosis between patients with and without chronic kidney disease (CKD) [3,4]. A previous optical coherence tomography (OCT) study from our group has shown that CKD lesions have greater lipid content and higher prevalence of calcification, but fibrous-cap thickness (FCT) and the prevalence of thin- cap fibroatheroma (TCFA) are similar between CKD and non-CKD [5]. The potential explanation for the lack of association between creatinine-based eGFR and coronary plaque vulnerability is that serum creatinine is affected by several nonkidney factors (age, sex, race, lean muscle mass, nutritional status, and physical activity) and is insensitive for mild to moderate renal dysfunction [6]. Cystatin C is a cysteine protease inhibitor produced by all nucleated cells at a constant rate and is freely filtered by the glomerulus and then metabolized by the proximal tubule [7]. Different from creatinine, cystatin C is less affected by nonkidney factors, and is more sensitive for Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.coronary-artery.com). Original research 135 0954-6928 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MCA.0000000000000452 Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved.