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Clinical Utility of Serum Cystatin C in Predicting Coronary Artery Disease

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Clinical Utility of Serum Cystatin C in Predicting Coronary Artery Disease Cardiology Journal 2010, Vol. 17, No. 4, pp. 374–380 Copyright © 2010 Via Medica ORIGINAL ARTICLE ISSN 1897–5593 Clinical utility of serum cystatin C in predicting coronary artery disease Mevlut Koc, Mustafa Kemal Batur, Osman Karaarslan, Gülcan Abali Adana Numune Education and Research Hospital, Department of Cardiology, Adana, Turkey Abstract Background: There is limited data regarding the clinical utility of cystatin C in patients with stable coronary artery disease (CAD). The aim of this study was to determine the predictive value of cystatin C for the presence and severity of CAD and the association between this protein and other biochemical risk factors for atherosclerosis in patients with suspected CAD. Methods: Ninety-four patients with CAD, and 92 patients without CAD but with cardiovascu- lar risk factors, were included in this study. Echocardiography and other pertinent laboratory examinations were performed. Subjects were divided into four groups according to their cystatin C quartile. Cystatin C groups were analyzed for the association with CAD characteristics. Results: The number of patients with CAD increased as the quartile of cystatin C increased, and there was a remarkable difference between quartiles (p < 0.001). Logistic regression analy- sis revealed independent predictors of incident CAD as cystatin C, hs-CRP, eGFR, HDL choles- terol and SBP (p = 0.005, p = 0.027, p = 0.017, p = 0.014 and p = 0.001, respectively). Moreover, cystatin C concentration was significantly correlated with CAD severity score (b = 0.258, p < 0.01). A cut-off value of 0.82 mg/L for cystatin C predicted incident CAD with a sensitivity and specificity of 75.5% and 75.0% respectively. Cystatin C concentration also correlated well with the atherosclerotic biochemical risk factors like homocysteine, creatinine and hs-CRP. Conclusions: Cystatin C could be a useful laboratory tool in predicting the presence and severity of CAD in daily practice. It also correlates significantly with biochemical risk factors for CAD, namely homocysteine, low HDL and CRP. (Cardiol J 2010; 17, 4: 374–380) Key words: cystatin C, coronary artery disease, markers of atherosclerosis Introduction widely in clinical settings, and this primarily de- pends on serum creatinine. However, serum crea- Renal dysfunction has been identified as a risk tinine is not sensitive enough to detect mild renal factor for the onset and prognosis of coronary athe- dysfunction [4]. Cystatin C is an endogenous gly- rosclerosis, and is regarded as a coronary artery cosylated protein produced in all nucleotide cells in disease (CAD) equivalent [1–3]. Although glome- the human body and a novel marker for renal func- rular filtration rate (GFR) is a sensitive method for tion [5]. It is more sensitive and specific for the es- assessing renal function, it has many drawbacks timation of GFR and less influenced by age, gen- such as difficulties in collecting urine. Therefore, der, race, muscle mass and medication, as compared for practical reasons, estimated GFR (eGFR) is used to serum creatinine [4, 6, 7]. The use of cystatin C Address for correspondence: Mevlut Koc, MD, Specialist of Cardiology, Adana Numune Education and Research Hospital, Department of Cardiology, Adana, 01330, Turkey, tel./fax: +90 322 338 69 33/+90 322 235 13 57, e-mail: [email protected] Received: 14.09.2009 Accepted: 20.01.2010 374 www.cardiologyjournal.org Mevlut Koc et al., Clinical utility of cystatin C for the assessment of renal filtration function has was carried out by using a VIVID 7 machine (GE recently been approved [8]. Healthcare, Little Chalfont, United Kingdom) with Previous studies have shown a close relation- a 2.5 or 3.5 MHz phased array transducer. A single ship between cystatin C and atherosclerotic disease experienced cardiologist (M.K.) performed echocar- [9–11]. Furthermore, a high level of cystatin C has diography and the mean of three consecutive cycles been related to suspected or confirmed acute coro- was used to drive the analysis. M-mode evaluation nary syndrome [12]. In 2007, the European Socie- was made according to the recommendations of the ty of Cardiology recommended the use of cystatin American Society of Echocardiography [18]. The C for predicting myocardial infarction and long-term left ventricular ejection fraction was calculated via mortality in patients with non-ST elevation acute modified Simpson’s technique. The left ventricular coronary syndrome [13]. The results of studies in- mass was calculated using the Devereux formula vestigating the value of cystatin C in anticipation [19] and indexed to body surface area. The presence of atherosclerosis in suspected stable CAD patients of left ventricular hypertrophy was accepted as left are controversial [10, 14–16]. Therefore, the clini- ventricular mass index (LVMI) > 134 g/m2 for men cal utility of cystatin C in stable CAD patients me- and > 110 g/m2 for women [20]. rits further investigation. The aim of this study was to investigate the Coronary angiography predictive value of cystatin C level for the presence All patients underwent coronary angiography, or severity of CAD and the association between this performed using standard Judkins techniques be- protein and other biochemical risk factors for athe- fore the start of the study. Two expert investiga- rosclerosis in patients with suspected CAD. tors, blinded to the clinical data, analyzed the an- giograms. The severity of coronary atherosclero- Methods sis was scored according to Gensini scoring [21] and three CAD groups were drawn up according to their Study group CAD severity score: namely normal coronary arteries Ninety-four CAD patients (70 male, 24 female, (normal coronary arteries or score 0), mild CAD mean age 57.8 ± 9.0 years) with significant coro- (score = 1–20) and severe CAD (score > 20). nary stenosis (> 50%) and 92 subjects without CAD but with cardiovascular risk factors (63 male, Assessment of cystatin C 29 female, mean age 55 ± 7 years) were included Venous blood was withdrawn from resting pa- in this cross-sectional study. Patients with severe tients, and put into ethylenediamine-tetraacetic acid renal dysfunction (creatinine > 2 mg/dL), history (EDTA)-containing tubes. Plasma was extracted of recent acute coronary syndrome, valvular heart after blood samples had been centrifuged at 3,000 g disease, life-threatening arrhythmias, acute and for 10 min at 0°C. Cystatin C was measured using chronic liver disease, infectious and inflammatory the particle-enhanced nephelometric immunoassay disease, and symptomatic heart failure were exclud- (PENIA) method and N Lateks cystatin C kit (Dade ed. All patients were in a stable condition and tak- Behring, Marburg, Germany) on a BN ProSpec pro- ing optimal medical therapy for their cardiovascu- tein analyzer (Dade Behring, Marburg, Germany) lar risk factors. The local ethics committee ap- no more than 20 minutes after venipuncture. proved the study and informed consent was obtained from all subjects. Statistical analysis The detailed histories of patients, including All analyses were performed using SPSS ver- demographics data and cardiovascular risk factors, sion 15.0 (SPSS Inc., Chicago, Illinois, USA). Cate- were recorded. Serum cholesterols, homocysteine, gorical variables of cystatin C groups were com- high sensitive C-reactive protein (hs-CRP), blood pared by the chi-square test. Continuous variables urea nitrogen and creatinine levels were measured were expressed as mean ± SD and compared by by routine laboratory methods. GFR was estimat- one-way analysis of variance. When indicated, a post ed by the Cockcroft-Gault formula: hoc test (Scheffe or Tamhane) was performed. Cor- [(140 age) × weight (kg)]/[72 × serum creati- relations between continuous variables were as- nine (mg/dL)] (× 0.85 for women) [17]. sessed using Pearson’s or Spearman’s rank corre- lation analysis. Multivariate logistic regression anal- Echocardiographic examination yses were performed to determine significant All echocardiographic examinations were ob- predictors of CAD. Significant variables in univari- tained at rest. Standard echocardiographic imaging ate analysis at a p < 0.1 level was entered in logis- www.cardiologyjournal.org 375 Cardiology Journal 2010, Vol. 17, No. 4 Table 1. Variables of study population according to cystatin C quartiles. Variable Serum cystatin C levels [mg/L] p (ANOVA) < 0.65 0.65–0.82 0.83–0.99 ≥ 1.0 (n = 47) (n = 46) (n = 46) (n = 47) Age (years) 54.2±5.0* 54.3±8.9D 56.7± 8.8 59.1±8.1 0.005 Male/female 39/8 29/17 34/12 31/16 0.170a Hypertension (%) 20 (42.6) 17 (36.9) 24 (52.2) 32 (68.1) 0.025a Systolic blood pressure [mm Hg] 130.6±15.9† 125.5±11.1 122.2±14.3 124.7±11.9 0.023 Diastolic blood pressure [mm Hg] 83.2±10.0 79.8±8.5 78.5±9.6 80.0±9.2 0.081 Diabetes (%) 22 (46.8) 13 (28.3) 17 (36.9) 16 (34.1) 0.344a Smoking (%) 14 (29.8) 16 (34.8) 15 (32.6) 19 (40.4) 0.337a Heart rate [bpm] 71.8±8.8 73.1±8.5 75.1±13.1 75.3±10.1 0.308 Creatinine [mg/dL] 0.77±0.19†, * 0.84±0.14D 0.93±0.15¶ 1.15±0.39 < 0.001 eGFR (%) 115±33†, ‡, * 106±24 100±22 78±28 < 0.001 Total cholesterol [mmol/L] 200±52‡ 169±32 186±45 187±46 0.010 HDL cholesterol [mmol/L] 52±10†, ‡, * 43±10 42±9.7 40±11 < 0.001 LDL cholesterol [mmol/L] 115±47 101±29 116±37 109±35 0.211 Triglycerides [mmol/L] 170±106 132±54D 168±82 181±80 0.026 Homocysteine [mg/dL] 1.8±0.7†, ‡, * 2.0±0.8 2.2±0.5 3.2±1.2 < 0.001 hs-CRP [mg/L] 5.3±4.0* 5.6±5.4 6.3±7.1 8.7±7.7 0.037 CAD severity score 1.5±5.3†, ‡, * 10.0±18.5D 18.7±19.2 25.2±21.3 < 0.001 Normal coronary arteries
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