Angiology
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Relationship of Neutrophil−Lymphocyte Ratio With the Presence, Severity, and Extent of Coronary Atherosclerosis Detected by Coronary Computed Tomography Angiography Göksel Açar, Serdar Fidan, Zulal Alnur Uslu, Sevim Turkday, Anil Avci, Elnur Alizade, Mehmet Emin Kalkan, Omer Naci Tabakci, Ibrahim Halil Tanboga and Ali Metin Esen ANGIOLOGY published online 19 February 2014 DOI: 10.1177/0003319714520954 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/02/17/0003319714520954
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Article
Relationship of Neutrophil–Lymphocyte Ratio With the Presence, Severity, and Extent of Coronary Atherosclerosis Detected by Coronary Computed Tomography Angiography
Angiology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714520954 ang.sagepub.com
Go¨ksel Ac¸ar, MD1, Serdar Fidan, MD1, Zulal Alnur Uslu, MD2, Sevim Turkday, MD1, Anıl Avci, MD1, Elnur Alizade, MD1, Mehmet Emin Kalkan, MD1, Omer Naci Tabakci, MD3, Ibrahim Halil Tanbog˘a, MD4, and Ali Metin Esen, MD1
Abstract We evaluated whether the neutrophil–lymphocyte ratio (NLR) was associated with the presence, severity, and extent of coronary atherosclerotic plaques detected by computed tomography angiography (CTA). We studied 238 patients who underwent dual-source 64-slice CTA for the assessment of coronary artery disease. Coronary arteries were evaluated on 16-segment basis and critical plaque was described as luminal narrowing >50%. In regression analysis, being in the third NLR tertile increased the risk of coronary atherosclerosis (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.15-4.43; P ¼ .023). When the severity of coronary atherosclerosis was assessed, being in the third NLR tertile increased the risk of critical luminal stenosis (OR, 2.60; 95% CI, 1.19-5.69; P ¼ .017). Although plaque morphology was not associated with NLR, the extent of coronary atherosclerosis was increased with higher NLR tertiles (P ¼ .001). Our results suggest that a higher NLR may be a useful additional measure to assess cardiovascular risk in clinical practice. Keywords neutrophil–lymphocyte ratio, coronary atherosclerosis, computed tomography angiography
Introduction Inflammation plays a major role in the onset and progression of atherosclerosis and its complications.1 The white blood cell (WBC) count and its subtypes are inflammatory biomarkers that predict cardiovascular (CV) outcomes.2,3 The neutrophil– lymphocyte ratio (NLR) has emerged as a useful predictor of CV risk.3-14 The NLR was also strongly related to the severity of coronary artery disease (CAD) at angiography.14-19 Although these studies used the NLR as an indicator of worse CAD within a population of patients with CAD, there are limited data about its use as a risk factor in patients free of clinically apparent CV disease. Recently, the relationship between NLR and coronary artery calcification was assessed in a healthy adult population,20 and higher NLR values were found to be independently associated with coronary artery calcification detected by computed tomography (CT) angiography (CTA). To our knowledge, there are no published data on the relationship between NLR and coronary atherosclerosis detected by coronary CTA, which has the advantage of
showing atherosclerotic plaques in the vessel wall in addition to the degree of luminal narrowing. Therefore, we assessed the relationship between the NLR and the presence, severity, and extent of atherosclerotic lesions in patients with suspected CAD undergoing coronary CTA.
1
Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey 2 Department of Radiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey 3 Department of Radiology, Sisli Etfal Educational and Research Hospital, Istanbul, Turkey 4 Department of Cardiology, Ataturk University School of Medicine, Erzurum, Turkey Corresponding Author: Go¨ksel Ac¸ar, Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Denizer Street, Cevizli Kavsagi, No: 2, 34846 Kartal, Istanbul, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at CARLETON UNIV on June 14, 2014
2
Angiology
Methods Study Population
Computed Tomography Angiography Data Analysis
This cross-sectional study was performed in a subset of patients admitted to our Cardiology Department for CV evaluation between January 2012 and December 2013 and in whom coronary CTA was performed for the suspicion of CAD after clinical assessment. Patients with a history of CAD, heart failure, renal dysfunction (serum creatinine levels 1.5 mg/dL), hepatic disorders, concomitant hematological disease, cancer, ongoing infection, or systemic inflammatory conditions were excluded. All patients provided details of their demographics, medical histories, and medication usages at the time of clinical consultation. After a 12-hour overnight fast, blood samples were taken from an antecubital vein. Total and differential leukocyte counts were measured by an automated hematology analyzer (Cell Dyn 3700 Abbott Diagnostics, Illinois, USA). Absolute cell counts were used in the analyses. All routine biochemical tests were carried out on an automatic biochemical analyzer (Beckman Coulter AU640, California, USA) at the time of CV evaluation. Diabetes was defined as fasting plasma glucose levels 126 mg/dL in multiple measurements or a history of taking diabetes medication. Hypertension was considered in patients with repeated blood pressure measurement 140/90 mm Hg or a history of taking antihypertensive drugs. Hyperlipidemia was defined as total cholesterol 200 mg/dL or treatment with a lipid-lowering agent. This study was approved by the local ethics committee and informed consent was obtained from each participant.
Coronary CTA All the scans were performed using dual-source 64-slice multidetector CT scanner (Aquilion; Toshiba Medical Systems, Japan). Patients with initial heart rates of 65 beats/min were given b blocker therapy according to the local protocols. Every participant received 0.4 mg of sublingual nitroglycerin 1 minute prior to contrast administration in order to dilate the coronary arteries. The coronary angiographic scan was obtained with injection of 80 mL of nonionic contrast medium (350 mg I/mL iomeprol; Bracco Omnipaque, Milano, Italy) at a flow rate of 5.5 mL/s followed by 50 mL of saline solution and contrast administration was controlled with bolus tracking. The scan parameters were detector collimation, 2 32 0.5 mm3; slice acquisition, 64 0.5 mm2; gantry rotation time, 350 milliseconds; temporal resolution, 83 milliseconds; pitch, 0.2 to 0.47 adapted to the heart rate; tube current, 400 mA/rotation; and tube potential, 120 kV. Scanning time was approximately 5.8 to 8.5 seconds, depending on the cardiac dimensions and pitch and breath holding was utilized to minimize motion artifact. Retrospective gating technique was used to synchronize data reconstruction with the electrocardiogram signal. The reconstructions were made in all cardiac phases at 50milliseconds intervals at a slice thickness of 0.5 mm and a reconstruction increment of 0.5 mm. The reconstruction interval with the fewest motion artifacts was chosen and used for further analysis.
All images were interpreted immediately after scanning by an experienced radiologist who was blinded to the clinic and laboratory results of the patients. Coronary artery plaque was defined as any clearly discernible structure attributable to the coronary artery wall in at least 2 independent image planes. Noncritical stenosis was defined as lesions causing 50% luminal narrowing, critical stenosis was defined as lesions causing >50% luminal narrowing. For categorization of the coronary plaque, the coronary system was divided into 16 separate segments based on a modified American Heart Association classification using original axial images, thin slice, maximal intensity projections, and cross-sectional reconstructions orthogonal to the long axis of each coronary segment (0.5 mm thickness).21 For each segment, coronary artery plaques were categorized as: (1) calcified plaque (defined as a CT density more than the contrast-enhanced coronary lumen), (2) noncalcified plaque (defined as a CT density less than the contrast-enhanced coronary lumen but greater than the surrounding connective tissue), and (3) mixed plaque (having both calcified and noncalcified components). The extent of coronary atherosclerosis was calculated as the number of coronary segments involved. All plaque components and significant stenosis were assessed on per segment basis.
Statistical Analysis Continuous variables are expressed as mean + standard deviation; categorical variables are expressed as percentages. The Kolmogorov-Smirnov test was used to verify the normality of distribution of continuous variables. The independent sample t test or the Mann-Whitney U test was used for the continuous variables and the chi-square test for categorical variables. The Kruskal-Wallis test was used to compare the differences in the number of affected coronary segments between the NLR tertiles. To determine the independent predictors of presence and severity of coronary atherosclerosis, multiple logistic regression analysis was performed by including the parameters that were significantly different between the groups. Statistical analysis was performed using the SPSS for Windows (version 19.0; SPSS Inc, Chicago, Illinois). A 2-sided P value of
http://ang.sagepub.com/
Relationship of Neutrophil−Lymphocyte Ratio With the Presence, Severity, and Extent of Coronary Atherosclerosis Detected by Coronary Computed Tomography Angiography Göksel Açar, Serdar Fidan, Zulal Alnur Uslu, Sevim Turkday, Anil Avci, Elnur Alizade, Mehmet Emin Kalkan, Omer Naci Tabakci, Ibrahim Halil Tanboga and Ali Metin Esen ANGIOLOGY published online 19 February 2014 DOI: 10.1177/0003319714520954 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/02/17/0003319714520954
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 - Feb 19, 2014 What is This?
Downloaded from ang.sagepub.com at CARLETON UNIV on June 14, 2014
Article
Relationship of Neutrophil–Lymphocyte Ratio With the Presence, Severity, and Extent of Coronary Atherosclerosis Detected by Coronary Computed Tomography Angiography
Angiology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714520954 ang.sagepub.com
Go¨ksel Ac¸ar, MD1, Serdar Fidan, MD1, Zulal Alnur Uslu, MD2, Sevim Turkday, MD1, Anıl Avci, MD1, Elnur Alizade, MD1, Mehmet Emin Kalkan, MD1, Omer Naci Tabakci, MD3, Ibrahim Halil Tanbog˘a, MD4, and Ali Metin Esen, MD1
Abstract We evaluated whether the neutrophil–lymphocyte ratio (NLR) was associated with the presence, severity, and extent of coronary atherosclerotic plaques detected by computed tomography angiography (CTA). We studied 238 patients who underwent dual-source 64-slice CTA for the assessment of coronary artery disease. Coronary arteries were evaluated on 16-segment basis and critical plaque was described as luminal narrowing >50%. In regression analysis, being in the third NLR tertile increased the risk of coronary atherosclerosis (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.15-4.43; P ¼ .023). When the severity of coronary atherosclerosis was assessed, being in the third NLR tertile increased the risk of critical luminal stenosis (OR, 2.60; 95% CI, 1.19-5.69; P ¼ .017). Although plaque morphology was not associated with NLR, the extent of coronary atherosclerosis was increased with higher NLR tertiles (P ¼ .001). Our results suggest that a higher NLR may be a useful additional measure to assess cardiovascular risk in clinical practice. Keywords neutrophil–lymphocyte ratio, coronary atherosclerosis, computed tomography angiography
Introduction Inflammation plays a major role in the onset and progression of atherosclerosis and its complications.1 The white blood cell (WBC) count and its subtypes are inflammatory biomarkers that predict cardiovascular (CV) outcomes.2,3 The neutrophil– lymphocyte ratio (NLR) has emerged as a useful predictor of CV risk.3-14 The NLR was also strongly related to the severity of coronary artery disease (CAD) at angiography.14-19 Although these studies used the NLR as an indicator of worse CAD within a population of patients with CAD, there are limited data about its use as a risk factor in patients free of clinically apparent CV disease. Recently, the relationship between NLR and coronary artery calcification was assessed in a healthy adult population,20 and higher NLR values were found to be independently associated with coronary artery calcification detected by computed tomography (CT) angiography (CTA). To our knowledge, there are no published data on the relationship between NLR and coronary atherosclerosis detected by coronary CTA, which has the advantage of
showing atherosclerotic plaques in the vessel wall in addition to the degree of luminal narrowing. Therefore, we assessed the relationship between the NLR and the presence, severity, and extent of atherosclerotic lesions in patients with suspected CAD undergoing coronary CTA.
1
Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey 2 Department of Radiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey 3 Department of Radiology, Sisli Etfal Educational and Research Hospital, Istanbul, Turkey 4 Department of Cardiology, Ataturk University School of Medicine, Erzurum, Turkey Corresponding Author: Go¨ksel Ac¸ar, Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Denizer Street, Cevizli Kavsagi, No: 2, 34846 Kartal, Istanbul, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at CARLETON UNIV on June 14, 2014
2
Angiology
Methods Study Population
Computed Tomography Angiography Data Analysis
This cross-sectional study was performed in a subset of patients admitted to our Cardiology Department for CV evaluation between January 2012 and December 2013 and in whom coronary CTA was performed for the suspicion of CAD after clinical assessment. Patients with a history of CAD, heart failure, renal dysfunction (serum creatinine levels 1.5 mg/dL), hepatic disorders, concomitant hematological disease, cancer, ongoing infection, or systemic inflammatory conditions were excluded. All patients provided details of their demographics, medical histories, and medication usages at the time of clinical consultation. After a 12-hour overnight fast, blood samples were taken from an antecubital vein. Total and differential leukocyte counts were measured by an automated hematology analyzer (Cell Dyn 3700 Abbott Diagnostics, Illinois, USA). Absolute cell counts were used in the analyses. All routine biochemical tests were carried out on an automatic biochemical analyzer (Beckman Coulter AU640, California, USA) at the time of CV evaluation. Diabetes was defined as fasting plasma glucose levels 126 mg/dL in multiple measurements or a history of taking diabetes medication. Hypertension was considered in patients with repeated blood pressure measurement 140/90 mm Hg or a history of taking antihypertensive drugs. Hyperlipidemia was defined as total cholesterol 200 mg/dL or treatment with a lipid-lowering agent. This study was approved by the local ethics committee and informed consent was obtained from each participant.
Coronary CTA All the scans were performed using dual-source 64-slice multidetector CT scanner (Aquilion; Toshiba Medical Systems, Japan). Patients with initial heart rates of 65 beats/min were given b blocker therapy according to the local protocols. Every participant received 0.4 mg of sublingual nitroglycerin 1 minute prior to contrast administration in order to dilate the coronary arteries. The coronary angiographic scan was obtained with injection of 80 mL of nonionic contrast medium (350 mg I/mL iomeprol; Bracco Omnipaque, Milano, Italy) at a flow rate of 5.5 mL/s followed by 50 mL of saline solution and contrast administration was controlled with bolus tracking. The scan parameters were detector collimation, 2 32 0.5 mm3; slice acquisition, 64 0.5 mm2; gantry rotation time, 350 milliseconds; temporal resolution, 83 milliseconds; pitch, 0.2 to 0.47 adapted to the heart rate; tube current, 400 mA/rotation; and tube potential, 120 kV. Scanning time was approximately 5.8 to 8.5 seconds, depending on the cardiac dimensions and pitch and breath holding was utilized to minimize motion artifact. Retrospective gating technique was used to synchronize data reconstruction with the electrocardiogram signal. The reconstructions were made in all cardiac phases at 50milliseconds intervals at a slice thickness of 0.5 mm and a reconstruction increment of 0.5 mm. The reconstruction interval with the fewest motion artifacts was chosen and used for further analysis.
All images were interpreted immediately after scanning by an experienced radiologist who was blinded to the clinic and laboratory results of the patients. Coronary artery plaque was defined as any clearly discernible structure attributable to the coronary artery wall in at least 2 independent image planes. Noncritical stenosis was defined as lesions causing 50% luminal narrowing, critical stenosis was defined as lesions causing >50% luminal narrowing. For categorization of the coronary plaque, the coronary system was divided into 16 separate segments based on a modified American Heart Association classification using original axial images, thin slice, maximal intensity projections, and cross-sectional reconstructions orthogonal to the long axis of each coronary segment (0.5 mm thickness).21 For each segment, coronary artery plaques were categorized as: (1) calcified plaque (defined as a CT density more than the contrast-enhanced coronary lumen), (2) noncalcified plaque (defined as a CT density less than the contrast-enhanced coronary lumen but greater than the surrounding connective tissue), and (3) mixed plaque (having both calcified and noncalcified components). The extent of coronary atherosclerosis was calculated as the number of coronary segments involved. All plaque components and significant stenosis were assessed on per segment basis.
Statistical Analysis Continuous variables are expressed as mean + standard deviation; categorical variables are expressed as percentages. The Kolmogorov-Smirnov test was used to verify the normality of distribution of continuous variables. The independent sample t test or the Mann-Whitney U test was used for the continuous variables and the chi-square test for categorical variables. The Kruskal-Wallis test was used to compare the differences in the number of affected coronary segments between the NLR tertiles. To determine the independent predictors of presence and severity of coronary atherosclerosis, multiple logistic regression analysis was performed by including the parameters that were significantly different between the groups. Statistical analysis was performed using the SPSS for Windows (version 19.0; SPSS Inc, Chicago, Illinois). A 2-sided P value of
