Angiology
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Neutrophil−Lymphocyte Ratio and Carotid−Intima Media Thickness in Patients With Behçet Disease Without Cardiovascular Involvement Cengiz Ozturk, Sevket Balta, Ilknur Balta, Sait Demirkol, Turgay Celik, Turker Turker, Atila Iyisoy and Meral Eksioglu ANGIOLOGY published online 25 March 2014 DOI: 10.1177/0003319714527638 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/03/24/0003319714527638
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Article
Neutrophil–Lymphocyte Ratio and Carotid–Intima Media Thickness in Patients With Behc¸et Disease Without Cardiovascular Involvement
Angiology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714527638 ang.sagepub.com
Cengiz Ozturk, MD1, Sevket Balta, MD2, Ilknur Balta, MD3, Sait Demirkol, MD1, Turgay Celik, MD1, Turker Turker, MD4, Atila Iyisoy, MD1, and Meral Eksioglu, MD5
Abstract Behc¸et disease (BD) is associated with endothelial dysfunction and chronic inflammation. The neutrophil–lymphocyte (N/L) ratio and carotid intima–media thickness (cIMT) are markers of inflammation and vascular risk, respectively. We assessed the relationship between cIMT values and N/L ratio in BD (65 patients and 62 control participants). There were statistically significant differences in N/L ratios and cIMT values between the patients with BD and control group (P < .001). There were moderate positive correlations between cIMT value, C-reactive protein, and N/L ratio in patients with BD. Receiver–operating characteristic curve analysis suggested that the optimum N/L ratio cutoff point for patients with BD was 1.29, with a sensitivity, specificity, negative predictive value, and positive predictive value of 97, 77, 96, and 75%, respectively (area under curve: 0.691, 95% confidence interval ¼ 0.600-0.782, P < .001). The N/L ratio may be a useful index of BD activity. Keywords Behc¸et disease, carotid intima–media thickness, neutrophil–lymphocyte ratio, disease activity
Introduction Behc¸et disease (BD) is a chronic, multisystemic, inflammatory disorder, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions.1 It is a systemic immunoinflammatory vasculitis.2,3 Several studies have reported indirect evidence of endothelial dysfunction (ED) in BD, such as increased blood levels of soluble thrombomodulin, E-selectin, and vascular endothelial growth factor (VEGF); these molecules were correlated with disease activity.2,4,5 Additionally, patients with BD have elevated levels of proinflammatory cytokines such as tumor necrosis factor a (TNF-a), interleukin (IL) 1b, IL-6 and the affected organs show neutrophil and lymphocyte infiltration.2 Some markers including IL-6, IL-1b, TNF-a, thrombomodulin, E-selectin, VEGF, and total homocysteine (tHcy) had been considered as inflammatory indicators in BD.6 In addition, the total white blood cell (WBC) count and its subtypes can be an indicator of systemic inflammation.7 The neutrophil–lymphocyte (N/L) ratio can easily be calculated.8 This calculation is very simple and cheap when compared with the other inflammatory cytokines including IL-6, IL-1b, TNF-a, thrombomodulin, E-selectin, and VEGF. Furthermore, the N/L ratio has been demonstrated to have a predictive power for cardiac and noncardiac diseases.9 The carotid intima–media thickness (cIMT) is a marker of cardiovascular risk.10
To the best of our knowledge, there is no study regarding the assessment of N/L ratio in patients with BD in the literature. Therefore, we evaluated the N/L ratio in patients with BD and compared it with control participants. We also investigated the relationship between cIMT and N/L ratio based on inflammatory activity.
Materials and Methods Selection of Patients We studied 65 patients (38 males, mean age: 37.6 + 11.7 years) who were diagnosed by the international diagnostic criteria of BD11 and 62 healthy controls (31 males, mean age: 1
Department of Cardiology, Gulhane Medical Academy, Ankara, Turkey Department of Cardiology, Eskis¸ ehir Military Hospital, Eskis¸ ehir, Turkey 3 Department of Dermatology, Eskisehir State Hospital, Ankara, Turkey 4 Department of Epidemiology, Gulhane Medical Academy, Ankara, Turkey 5 Department of Dermatology, Ankara Training and Research Hospital, Ankara, Turkey 2
Corresponding Author: Sevket Balta, Department of Cardiology, Eskisehir Military Hospital, Vis¸ nelik Mah, Atatu¨rk Cd. 26020 Akarbas¸ ı/ Eskis¸ ehir, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at University of Leeds on November 1, 2014
2
Angiology
35.0 + 10.6 years). Part of these patients with BD (n ¼ 33) was included in a previous study.12 Body height and weight, blood pressure (BP), and body mass index were measured. A control group was selected in our outpatient clinic. These patients did not have any chronic illness. They had not received any medication and were not found to have any pathology. The study was conducted in accordance with the Helsinki Declaration. The local ethics committee approved the study protocol. On physical examination, the presence of the following clinical features of BD was considered as active disease: oral ulceration, genital ulceration, skin lesions, ocular lesions, active major vessel disease, and active major organ involvement including active gastrointestinal or neurological lesions. Scoring for classification into active disease category was carried out according to the clinical activity index proposed by ‘‘the BD Research Committee of Japan’’13 in 2003. Exclusion criteria were refusal to participate in the study, BD with vascular involvement, hypertension, anemia, diabetes mellitus, hyperlipidemia, coronary artery disease, smoking, alcohol consumption, left ventricular dysfunction (left ventricular ejection fraction 1.5 mg/dL, aspartate aminotransferase, and alanine transaminase > 2 the upper limit of normal), known malignancy, local or systemic infection, previous history of infection (140 mm Hg and/or diastolic BP >90 mm Hg or if the individual was taking antihypertensive medication. Diabetes was defined as a fasting blood glucose level (>126 mg/dL) or current diet or medication to lower blood glucose.
Laboratory Measurements Blood samples were drawn without stasis at 7 to 8 AM after 20 minutes of supine rest, following fasting for 12 hours. Total plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured by an enzymatic colorimetric
method using an Olympus AU 600 autoanalyzer and reagents from Olympus Diagnostics GmbH (Hamburg, Germany). Low-density lipoprotein cholesterol levels were calculated by the Friedewald formula.15 Blood glucose was measured by the glucose oxidase method. The blood was collected in tripotassium EDTA (7.2 mg) tubes. Hematological parameters including hemoglobin, WBC count, and platelet count were analyzed using an LH 780 analyzer (Beckman Coulter Inc, Miami, Florida).
Measurement of cIMT All patients were evaluated in the supine position by highresolution ultrasound using a Philips IE 33 6.0 (Andover, Massachusetts) equipped with an L 11-3 broadband linear array transducer. The transducer was manipulated so that the near and far walls of the common carotid artery (CCA) were parallel to the transducer footprint and the lumen diameter was maximized in the longitudinal plane. A region 1 cm proximal to the carotid bifurcation was identified and the cIMT of the far wall was evaluated as the distance between the lumen– intima interface and the media–adventitia interface. The cIMT measurement was obtained from 4 contiguous sites at 1 mm intervals and the average of the 4 measurements was used. Then, the measurements were taken from both right and left CCAs, and the average of these values was calculated. All measurements were made manually on still images obtained during sonographic scanning. Carotid plaques were excluded while measuring cIMT. The intraobserver variability of ultrasonographic measurements was
http://ang.sagepub.com/
Neutrophil−Lymphocyte Ratio and Carotid−Intima Media Thickness in Patients With Behçet Disease Without Cardiovascular Involvement Cengiz Ozturk, Sevket Balta, Ilknur Balta, Sait Demirkol, Turgay Celik, Turker Turker, Atila Iyisoy and Meral Eksioglu ANGIOLOGY published online 25 March 2014 DOI: 10.1177/0003319714527638 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/03/24/0003319714527638
Published by: http://www.sagepublications.com
Additional services and information for Angiology can be found at: Email Alerts: http://ang.sagepub.com/cgi/alerts Subscriptions: http://ang.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Mar 25, 2014 What is This?
Downloaded from ang.sagepub.com at University of Leeds on November 1, 2014
Article
Neutrophil–Lymphocyte Ratio and Carotid–Intima Media Thickness in Patients With Behc¸et Disease Without Cardiovascular Involvement
Angiology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714527638 ang.sagepub.com
Cengiz Ozturk, MD1, Sevket Balta, MD2, Ilknur Balta, MD3, Sait Demirkol, MD1, Turgay Celik, MD1, Turker Turker, MD4, Atila Iyisoy, MD1, and Meral Eksioglu, MD5
Abstract Behc¸et disease (BD) is associated with endothelial dysfunction and chronic inflammation. The neutrophil–lymphocyte (N/L) ratio and carotid intima–media thickness (cIMT) are markers of inflammation and vascular risk, respectively. We assessed the relationship between cIMT values and N/L ratio in BD (65 patients and 62 control participants). There were statistically significant differences in N/L ratios and cIMT values between the patients with BD and control group (P < .001). There were moderate positive correlations between cIMT value, C-reactive protein, and N/L ratio in patients with BD. Receiver–operating characteristic curve analysis suggested that the optimum N/L ratio cutoff point for patients with BD was 1.29, with a sensitivity, specificity, negative predictive value, and positive predictive value of 97, 77, 96, and 75%, respectively (area under curve: 0.691, 95% confidence interval ¼ 0.600-0.782, P < .001). The N/L ratio may be a useful index of BD activity. Keywords Behc¸et disease, carotid intima–media thickness, neutrophil–lymphocyte ratio, disease activity
Introduction Behc¸et disease (BD) is a chronic, multisystemic, inflammatory disorder, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions.1 It is a systemic immunoinflammatory vasculitis.2,3 Several studies have reported indirect evidence of endothelial dysfunction (ED) in BD, such as increased blood levels of soluble thrombomodulin, E-selectin, and vascular endothelial growth factor (VEGF); these molecules were correlated with disease activity.2,4,5 Additionally, patients with BD have elevated levels of proinflammatory cytokines such as tumor necrosis factor a (TNF-a), interleukin (IL) 1b, IL-6 and the affected organs show neutrophil and lymphocyte infiltration.2 Some markers including IL-6, IL-1b, TNF-a, thrombomodulin, E-selectin, VEGF, and total homocysteine (tHcy) had been considered as inflammatory indicators in BD.6 In addition, the total white blood cell (WBC) count and its subtypes can be an indicator of systemic inflammation.7 The neutrophil–lymphocyte (N/L) ratio can easily be calculated.8 This calculation is very simple and cheap when compared with the other inflammatory cytokines including IL-6, IL-1b, TNF-a, thrombomodulin, E-selectin, and VEGF. Furthermore, the N/L ratio has been demonstrated to have a predictive power for cardiac and noncardiac diseases.9 The carotid intima–media thickness (cIMT) is a marker of cardiovascular risk.10
To the best of our knowledge, there is no study regarding the assessment of N/L ratio in patients with BD in the literature. Therefore, we evaluated the N/L ratio in patients with BD and compared it with control participants. We also investigated the relationship between cIMT and N/L ratio based on inflammatory activity.
Materials and Methods Selection of Patients We studied 65 patients (38 males, mean age: 37.6 + 11.7 years) who were diagnosed by the international diagnostic criteria of BD11 and 62 healthy controls (31 males, mean age: 1
Department of Cardiology, Gulhane Medical Academy, Ankara, Turkey Department of Cardiology, Eskis¸ ehir Military Hospital, Eskis¸ ehir, Turkey 3 Department of Dermatology, Eskisehir State Hospital, Ankara, Turkey 4 Department of Epidemiology, Gulhane Medical Academy, Ankara, Turkey 5 Department of Dermatology, Ankara Training and Research Hospital, Ankara, Turkey 2
Corresponding Author: Sevket Balta, Department of Cardiology, Eskisehir Military Hospital, Vis¸ nelik Mah, Atatu¨rk Cd. 26020 Akarbas¸ ı/ Eskis¸ ehir, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at University of Leeds on November 1, 2014
2
Angiology
35.0 + 10.6 years). Part of these patients with BD (n ¼ 33) was included in a previous study.12 Body height and weight, blood pressure (BP), and body mass index were measured. A control group was selected in our outpatient clinic. These patients did not have any chronic illness. They had not received any medication and were not found to have any pathology. The study was conducted in accordance with the Helsinki Declaration. The local ethics committee approved the study protocol. On physical examination, the presence of the following clinical features of BD was considered as active disease: oral ulceration, genital ulceration, skin lesions, ocular lesions, active major vessel disease, and active major organ involvement including active gastrointestinal or neurological lesions. Scoring for classification into active disease category was carried out according to the clinical activity index proposed by ‘‘the BD Research Committee of Japan’’13 in 2003. Exclusion criteria were refusal to participate in the study, BD with vascular involvement, hypertension, anemia, diabetes mellitus, hyperlipidemia, coronary artery disease, smoking, alcohol consumption, left ventricular dysfunction (left ventricular ejection fraction 1.5 mg/dL, aspartate aminotransferase, and alanine transaminase > 2 the upper limit of normal), known malignancy, local or systemic infection, previous history of infection (140 mm Hg and/or diastolic BP >90 mm Hg or if the individual was taking antihypertensive medication. Diabetes was defined as a fasting blood glucose level (>126 mg/dL) or current diet or medication to lower blood glucose.
Laboratory Measurements Blood samples were drawn without stasis at 7 to 8 AM after 20 minutes of supine rest, following fasting for 12 hours. Total plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured by an enzymatic colorimetric
method using an Olympus AU 600 autoanalyzer and reagents from Olympus Diagnostics GmbH (Hamburg, Germany). Low-density lipoprotein cholesterol levels were calculated by the Friedewald formula.15 Blood glucose was measured by the glucose oxidase method. The blood was collected in tripotassium EDTA (7.2 mg) tubes. Hematological parameters including hemoglobin, WBC count, and platelet count were analyzed using an LH 780 analyzer (Beckman Coulter Inc, Miami, Florida).
Measurement of cIMT All patients were evaluated in the supine position by highresolution ultrasound using a Philips IE 33 6.0 (Andover, Massachusetts) equipped with an L 11-3 broadband linear array transducer. The transducer was manipulated so that the near and far walls of the common carotid artery (CCA) were parallel to the transducer footprint and the lumen diameter was maximized in the longitudinal plane. A region 1 cm proximal to the carotid bifurcation was identified and the cIMT of the far wall was evaluated as the distance between the lumen– intima interface and the media–adventitia interface. The cIMT measurement was obtained from 4 contiguous sites at 1 mm intervals and the average of the 4 measurements was used. Then, the measurements were taken from both right and left CCAs, and the average of these values was calculated. All measurements were made manually on still images obtained during sonographic scanning. Carotid plaques were excluded while measuring cIMT. The intraobserver variability of ultrasonographic measurements was
