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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 3  |  Page : 439-447

Value of 2D echo calcium score and neutrophil/lymphocyte ratio as simple tools for the prediction of coronary artery disease documented by multislice computed tomography in type II diabetic patients


1 Department of Cardiology, El Moqattem Insurance Hospital, Egypt
2 Department of Cardiology, Faculty of Medicine for Girls Al Azhar University, Egypt
3 Department of Cardiology, Kobry El-Kobba Military Medical Complex, Cairo, Egypt

Date of Submission16-Jun-2020
Date of Decision18-Jun-2020
Date of Acceptance23-Jun-2020
Date of Web Publication2-Oct-2020

Correspondence Address:
MBBCh Samar A Nasreldeen
Department of Cardiology, El Moqattem Insurance Hospital, Mansoura, 35511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_67_20

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  Abstract 


Background Early detection of coronary artery disease (CAD) among patients with type II diabetes mellitus (DM) constitutes an important task. Neutrophil-lymphocytic ratio (NLR) and echo calcium score (eCS) have been recently identified as independent predictors of CAD.
Aim The study aimed to assess the value of 2D echo calcium score and NLR as simple tools for the prediction of CAD documented by multislice computed tomography in type II diabetic patients.
Patients and methods The study included 40 male patients with type II DM and known risk factors for CAD, who were referred for coronary computed tomography (CT) due to suspected CAD. NLR and eCS were assessed in all patients. Coronary calcium score and the presence of obstructive CAD were assessed by CT coronary angiography.
Results Patients were divided into two groups according to the presence of CAD; group I (18 patients) with nonobstructive CAD and group II (22 patients) with obstructive CAD. The authors found that patients in group II had significantly higher NLR, eCS, and coronary artery calcium score (CACS) compared with group I. There was a weak positive correlation between NLR and coronary calcium score and a strong positive correlation between eCS and CACS. The best sensitivity and specificity of eCS and NLR were 77.3, 66.7 and 77.3, 61.1%, respectively, when used alone to predict obstructive CAD. However, when combining NLR and eCS, the capability to predict obstructive CAD increased with sensitivity (90.9%) and specificity (72.2%).
Conclusion NLR and eCS had the capability to predict obstructive CAD detected by CT coronary angiography in patients with type II DM.

Keywords: coronary artery disease, echo calcium score, neutrophil lymphocyte ratio


How to cite this article:
Nasreldeen SA, Abdel Hady BM, Abd Elaziz OH, Ahmed AM. Value of 2D echo calcium score and neutrophil/lymphocyte ratio as simple tools for the prediction of coronary artery disease documented by multislice computed tomography in type II diabetic patients. Sci J Al-Azhar Med Fac Girls 2020;4:439-47

How to cite this URL:
Nasreldeen SA, Abdel Hady BM, Abd Elaziz OH, Ahmed AM. Value of 2D echo calcium score and neutrophil/lymphocyte ratio as simple tools for the prediction of coronary artery disease documented by multislice computed tomography in type II diabetic patients. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 28];4:439-47. Available from: http://www.sjamf.eg.net/text.asp?2020/4/3/439/296954




  Introduction Top


Type II diabetes mellitus (DM) is a prevalent disease affecting many people all over the world [1]. Coronary artery disease (CAD) is the leading cause of death in the Western world; although multifactorial in its origin, immunological and inflammatory events are considered to play central roles in the initiation and progression of atherosclerotic plaques [2].

Several studies have demonstrated the important role of neutrophil in all stages of atherosclerosis and plaque destabilization leading to acute coronary syndrome [3]. Coronary computed tomography angiography (CCTA) is a noninvasive method allowing accurate assessment of CAD. CCTA provides information about the vessel wall and composition of plaques in addition to the degree of stenosis [4]. 2D echocardiography is a noninvasive method to detect through the estimation of calcium score present in aortic valve calcification (AVC), mitral annulus calcification (MAC), and aortic root and papillary muscle calcification [5].

While CCTA remains the reference method to quantify coronary and noncoronary cardiac calcium, the use of echocardiography for this purpose, if validated against CCTA, would portend inherent advantages of being low cost, portability, and radiation safety, becoming a potentially simple adjunct to clinical scores for individualized risk prediction [6].


  Aim Top


The study was conducted to assess the value of 2D echo calcium score and neutrophil/lymphocyte ratio as simple tools for the prediction of CAD documented by multislice CT in type II diabetic patients.


  Patients and methods Top


This prospective study was conducted on 40 male patients during the period from December 2017 to December 2018 at Kobry El-Kobba Military Medical Complex.

Written informed consent was taken from all participants before enrollment into the study and the study was approved by the Ethics Committee of Faculty of Medicine for Girls, Al Azhar University.

Inclusion criteria

Patients with type II DM in the age range of 30–65 years old with multiple risk factors of ischemic heart disease or symptoms suggestive of CAD were included in the study.

Exclusion criteria

Patients with a history of revascularization (either by percutaneous coronary intervention or bypass surgery), any contraindication to multislice computed tomography (MSCT) (like dye allergy, heart rate more than 80 beats/min, atrial fibrillation or frequent extra systole, renal impairment with creatinine >1.5, etc.), patients with known factors influencing immunological and inflammatory markers, major trauma, surgery in the last 30 days, and blood cell diseases were excluded from the study.

All patients were subjected to the following:
  1. Complete clinical workup including:
    1. Demographic data (age and sex).
    2. Thorough medical history taking of patient’s illness and clinical examination with special emphasis on risk factors of CAD, duration, and medical treatment of DM.
  2. Twelve-lead surface ECG.
  3. Laboratory investigations: for the determination of HbA1C, lipid profile, complete blood count [assessment of neutrophil count, neutrophil/lymphocytic ratio (NLR)], and serum creatinine.
  4. Conventional echocardiography:
    • All patients had transthoracic echocardiographic study (TTE) using SIEMENS ACUSON ×700, using 4V1c transducer with frequency bandwidth 1.0–4.0 MHZ. Examination was done with the patient in the left lateral position and simultaneous ECG physio signal was displayed with all recorded echo images and loops.
    • All images and loops of at least three conducted cycles were recorded and analyzed: TTE M-mode, 2D Doppler and color flow images. All measurements and evaluation were performed according to the guidelines of the American Society of Echocardiography [7] with special concern to 2D study which was used to assess cardiac calcium score with adjustment of gain settings in which:
    • AVC was defined as focal areas of increased echogenicity and thickening of the aortic valve leaflets in the absence of aortic stenosis (velocity across the valve <2.5 m/s). Each aortic valve leaflet was graded on a scale of 0 (normal) to 3 (severe) according to leaflet thickening and calcific deposits, which was taken from apical five-chambers, long-axis, and short-axis parasternal (at the level of aorta and left atrium) views as shown in [Figure 1]. The highest score for a given cusp was assigned as the overall degree of AVCs [6].MAC was defined as an intense and bright echo-producing structure located at the junction of the atrioventricular groove and posterior mitral valve leaflet as shown in [Figure 2], and was measured from the anterior and posterior leaflets and judged on a scale of 0 (normal) to 3 (severe), which was taken from apical four-chamber view [6].Papillary muscle calcium was defined as a bright echo involving the head of one or both papillary muscles, which was taken from the short-axis parasternal view at the mid-level [6].Aortic root calcium was defined as a focal or diffuse area of increased echo reflectance and thickening in the aortic root on the parasternal long-axis view [6].
      Figure 1 Apical five-chamber view showed severe aortic valve thickening and calcification (taking three points).

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      Figure 2 Apical four-chamber view showed moderate mitral annulus calcification (taking two points).

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    • Accordingly, a final score was derived as the sum of all identified cardiac calcific deposits and was in the range of 0 (no calcium visible) to 8 (extensive cardiac and aortic root calcific deposits) [6].
  5. Coronary multidetector computed tomography (MDCT):
    1. Scan protocol: CCTA was performed with a dual-source CT (DSCT) (Siemens Healthcare, Siemens Medical Solutions USA, Inc., Ultrasound 22010 S.E. 51st Street Issaquah, WA, USA) scan. Heart rates of all patients were determined 1 h before examinations. If the heart rate was greater than or equal to 65 bpm, the patient was orally administered 40–80 mg of oral beta blocker propranolol hydrochloride (Inderal at 40 mg/tablet) except for those with contraindications to beta blocker we used instead Ivabradine 5–7.5 mg. A 0.5 mg sublingual dose of nitroglycerin was administered just before the scan [8].
    2. CCTA analysis: the severity of luminal diameter stenosis was scored as none or normal (0% luminal stenosis), minimal obstruction (plaques with a lumen narrowing of <25%), mild obstruction (plaques with stenosis from 25 to 49%), moderate obstruction (plaques with stenosis from 50 to 69%), severe obstruction (plaques with stenosis from 70 to 99%), and totally occluded lumen (100%) as shown in [Figure 3],[Figure 4],[Figure 5] [9].
      Figure 3 MSCT showed proximal and mid 60–70% stenotic lesions in RCA, followed by distal 80% stenotic lesion. MSCT, multislice computed tomography; RCA, right coronary artery.

      Click here to view
      Figure 4 MSCT image showed proximal LAD 70% stenotic lesion. LAD, left anterior descending artery; MSCT, multislice computed tomography. MSCT, multislice computed tomography.

      Click here to view
      Figure 5 MSCT image showed a totally occluded LCX. LCX, left circumflex artery; MSCT, multislice computed tomography.

      Click here to view
    3. An overall Agatston score was recorded for each patient to calculate coronary artery calcium score (CACS). The CACS was identified as a dense area in the coronary artery exceeding the threshold of 130 HU as shown in [Figure 6] [10].
      Figure 6 MSCT image showed CACS: 12.6. CACS, coronary artery calcium score; MSCT, multislice computed tomography.

      Click here to view
  6. Invasive coronary angiography (ICA): was performed for six patients who had CACS greater than or equal to 400.


Statistical analysis

Results were analyzed using the SPSS version 23.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and NCSS 12 for Windows (NCSS LCC., Kaysville, Utah, USA).

Data were expressed as mean±SD. The following statistical tests were used for analysis of data:
  1. Student’s t test: for testing statistical difference between means of the two groups in each classification for normally distributed variables. Normality was confirmed by the central limit theorem.
  2. Pearson’s correlation test with the determination of the correlation coefficient (r) to test a positive or negative relationship between two variables.
    • *A P value less than 0.05 was considered statistically significant.
  3. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for each of the echo calcium score (eCS) and NLR that could predict the severity of obstructive CAD among the study group.
  4. Multiple logistic regression: used to detect the strongest parameter which can predict obstructive CAD among the study group.



  Results Top


Basic demographic criteria of the study population are summarized in [Table 1]:
Table 1 Baseline demographic data of the whole study population

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Baseline CT coronary angiographic data are summarized in [Table 2].
Table 2 Baseline computed tomography coronary angiographic data

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Significant coronary artery obstruction was detected in 22 (55%) patients of the study. We found that 34 (85%) patients had CACs less than 400, while only six (15%) patients had CACS more than or equal to 400 ([Table 2]).

All six patients with CACS more than or equal to 400 underwent ICA with subsequent revascularization in five patients and medical treatment in one patient. All six patients had high NLR (2.68±0.46), and also had high eCS (7.3±0.8).

The study population was divided into two groups according to the presence of obstructive CAD:
  1. Group I: included 18 (45%) patients with nonobstructive CAD.
  2. Group II: included 22 (55%) patients with obstructive CAD.


Comparison between group I and group II as regards demographic data

The study revealed significant statistical increase in age in group II compared with group I, but there was no significant statistical difference between them as regards the other parameters as shown in [Table 3].
Table 3 Comparison between group I and group II regarding the demographic data

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Comparison between group I and group II as regards differential leukocytic count

The study revealed significant difference between the two groups as regards lymphocytes count, being lower in group II compared with group I. Also, there was statistically significant difference between the two groups as regards NLR, being higher in group II compared with group I, while there was no statically significant difference between them as regards other variables ([Table 4]).
Table 4 Comparison between group I and group II regarding the differential leukocytic count and HbA1c

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Comparison between group I and group II regarding echocardiographic calcium grading and score

The study showed statistically significant increase in mitral annular, aortic valve sclerosis, and total eCS in group II compared with group I, while there was no statistically significant difference between them as regards other tested variables as shown in [Table 5].
Table 5 Comparison between group I and group II regarding echo calcium score

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Comparison between group I and group II regarding CT coronary angiographic data

The study showed significant increase in CACS in group II patients compared with patients in group I ([Table 6]).
Table 6 Comparison between group I and group II regarding computed tomography coronary angiographic data

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Correlation between NLR, eCS, and coronary calcium score

The study showed that there was strong positive correlation between total eCS and coronary calcium score while there was weak positive correlation between NLR and coronary calcium score as shown in [Table 7].
Table 7 Correlation between NLR, eCS, and CCS

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ROC curve analysis for NLR and eCS in predicting obstructive CAD as shown in [Table 8] and [Figure 7]:
Table 8 Predictive performance of NLR and eCS for obstructive CAD; ROC curve analysis

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Figure 7 Receiver operating characteristic curve analysis for neutrophil-lymphocytic ratio and total echo calcium score in predicting obstructive coronary artery disease.

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ROC curve analysis showed that the eCS best cutoff value was greater than or equal to 6 with a sensitivity of 77.3% and specificity of 66.7% when used alone to predict obstructive CAD.

While the NLR best cutoff was greater than or equal to 2.2 with a sensitivity of 77.3% and specificity of 61.1% when used alone to predict obstructive CAD.

When combining NLR and eCS the capability to predict obstructive CAD increased with a sensitivity of 90.9% and specificity of 72.2%.

We performed a binary logistic regression with enter model to detect the strongest parameter that can predict obstructive CAD. We included age, and among these parameter which included; NLR, eCS and CACS, we found that eCS was the strongest parameter in prediction of the severity of CAD.


  Discussion Top


Type II DM is a common metabolic disorder predisposing to atherosclerotic cardiovascular disease [11]. Several studies have suggested that high NLR was associated with the severity of CAD, and it might be useful for predicting severe stenosis in CAD [12]. Similarly, AVC, MAC, or other semiquantitative scores of cardiac calcium using echocardiography have also been associated with CAD and more importantly adverse cardiac prognosis [5].

This study was conducted to assess the value of 2D eCS and NLR to predict the risk of developing obstructive CAD detected by MSCT in type II DM patients.

The study showed significantly higher NLR among patients with obstructive CAD compared with patients with nonobstructive CAD and there was positive correlation between NLR and CACS (r=0.320, P=0.44). This result is consistent with the results of Verdoia et al. [13], who studied the association of NLR with the prevalence and extent of CAD in consecutive patients undergoing elective or urgent coronary angiography and their study showed that NLR was independently associated with the prevalence and severity of CAD.

Moreover, in agreement with our results, Choi et al. [14] reported that patients with CAD and high NLR have a greater possibility of having a vulnerable plaque and higher inflammatory status, which can lead to acute coronary events.

Also, in accordance to our results, Hong et al. [15] reported that the count of WBC and its differential types were useful, inexpensive, and widely available markers of inflammation and can predict the risk and severity of CAD in diabetic patients with stable CAD.

In our study, the cutoff value of NLR associated with the presence of obstructive CAD was greater than or equal to 2.2. A comparable value was also reported in the study of Aygün and Efe [16] who found that the presence of obstructive CAD occurred when NLR was more than 2.05. However, in the study of Azab et al. [17], they reported that patients with NLR more than 2.36 showed more serious major adverse cardiac events including acute myocardial infarction, revascularization, and cardiovascular death. The differences in the cutoff values in the three studies were in the acceptable range.The study showed that eCS was significantly high in patients with obstructive CAD compared with those with nonobstructive CAD (P=0.003) and there was strong positive correlation between eCS and CACS (r=640, P=0.001). Moreover, binary logistic regression analysis of most of the examined variables in our study identified eCS as the strongest predictor of obstructive CAD. This result is consistent with the results of Gaibazzi et al. [6], who also reported positive correlation between eCS and high CACS detected by MSCT and concluded that eCS was a simple easily obtainable tool that can predict the severity of CAD among patients with DM.

This study showed also that the cutoff value of eCS associated with the presence of obstructive CAD was greater than or equal to 6. This result is discordant with the results of Nucifora et al. [18] who reported a lower cutoff value more than 2. The differences in these cutoff values confirm the presence of gray zone, as in most scores in medicine, in which results should be interpreted with clinical caution, and it may be also due to differences in the study design and sample size of the study population.

The study demonstrated that combined NLR and eCS improved sensitivity, specificity, and positive predictive value of detection of obstructive CAD better than either tool when used alone for this task. To the best of our knowledge, this study was the first to combine these two simple easily obtainable tools in the stratification of diabetic patients prone to CAD.

Study limitation

Our study has some limitation as it did not represent all races, did not include all genders, had a small sample size, and the eCS requires some operator experience to control gain settings in order to obtain reproducible results; thus, CCTA remains a more objective approach in this regard.


  Conclusion Top


High NLR and eCS are associated with the severity of CHD and can be used to predict obstructive CAD in patients with type II DM.

Recommendation

The results of this study need further evaluation in larger, prospective, randomized studies including a larger sample size and longer periods of follow up.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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