Neutrophil to Lymphocyte Ratio Predicts SYNTAX Score in Patients

With Non-ST Segment Elevation Myocardial Infarction

Serkan Kurtul,1 MD, Bahadir Sarli,2 MD, Ahmet Oguz Baktir,2 MD, Melih Demirbas,2 MD,
Hayrettin Saglam,2 MD, Yasemin Doğan,2 MD, Omer Sahin,2 MD, Mahmut Akpek,2 MD,
Huseyin Odabas,2 MD, Huseyin Arinc,2 MD, and Mehmet G Kaya,3 MD

Summary
In this study we aimed to investigate whether there is an association between the neutrophil to lymphocyte ratio
(NLR) and severity of coronary artery disease (CAD) in patients with non-ST segment elevation myocardial infarction
(NSTEMI) using the SYNTAX score (SXscore). A total of 414 patients with NSTEMI who underwent coronary angiog-
raphy were enrolled in the study. NLR was measured for all patients at presentation. The study population was then di-
vided into 3 tertiles based on the SYNTAX trial results.1) The low syntax group (n = 329) was defined as those with an
SXscore ≤ 22, the intermediate syntax group (n = 58) was defined as an SXscore ≥ 23 and < 33, and the high syntax
group (n = 27) as those with an SXscore ≥ 33. NLR was significantly lower in patients with a low SXscore compared to
patients with an intermediate SXscore or high SXscore (3.7 ± 4 to 4.6 ± 2 and 7.9 ± 4, P < 0.001). Linear regression
analysis revealed that NLR (coefficientβ = 0.380, 95%CI: 1.165-1.917, P < 0.001) was significantly associated with the
SXscore in patients with NSTEMI. Our results indicate that NLR is independently associated with the severity of CAD
in patients with NSTEMI. (Int Heart J 2015; 56: 18-21)

Key words: Inflammation, Plaque burden, Acute coronary syndrome

N
 on-ST segment elevation myocardial infarction
(NSTEMI) is one of the leading causes of death in
patients with coronary artery disease (CAD).2,3) Pa-
tients with NSTEMI tend to have multivessel CAD and similar
cardiovascular mortality compared to patients with STEMI.
Several treatment strategies including intensive medical treat-
ment and invasive procedures have been successful in decreas-
ing the morbidity and mortality of NSTEMI.4) However, the
severity of CAD in coronary angiography is the leading factor
in determining the most useful treatment strategy. The SYN-
TAX score (SXscore) is an anatomic scoring system which
quantifies the properties of a lesion including complexity, mor-
phology, and location in the coronary vasculature.5) It has been
shown that the SXscore may predict short and long-term mor-
tality in patients with CAD intervention.6)
The role of inflammation in the initiation and progression
of coronary atherosclerosis is well described.7-10) Increased lev-
els of inflammatory markers have been found in association
with the severity of coronary atherosclerosis and prognosis in
acute coronary syndromes.11,12) The neutrophil to lymphocyte
ratio (NLR) is an indicator of baseline inflammatory response.
Although the predictive value of NLR on the severity of
CAD in patients with STEMI and stable CAD is well known,
its role in NSTEMI is less clear. Therefore, the aim of the
present study was to investigate whether there is an association
between NLR and severity of CAD in patients with NSTEMI
using the SXscore.
Methods
Patient selection: A total of 414 patients (292 males, mean
age, 63.8 ± 12 years) were consecutively selected from among
patients with NSTEMI who underwent coronary angiography
in the catheterization laboratory of the Kayseri Education and
Research Hospital between July 2012 and November 2013.
The control group consisted of 35 patients (22 males, mean
age, 64.4 ± 8 years) without CAD who underwent coronary
angiography for anginal symptoms or suspected CAD in non-
invasive tests. NSTEMI was defined as having typical chest
pain and a positive troponin-I level (defined in our clinical lab-
oratory as > 0.01 ng/mL) without any evidence of ST segment
elevation on 12-lead electrocardiogram. To diminish any con-
founders that might influence NLR, patients with a history of
congestive heart failure, previous percutaneous coronary inter-
vention, coronary artery bypass grafting surgery history, active
infectious disease, inflammatory or immunologic disease, cir-
rhosis, peripheral arterial disease, chronic obstructive pulmo-
nary disease, chronic kidney disease, malignancy, or cardio-
genic shock on admission were excluded.

From the 1 Department of Cardiology, Kahramanmaras State Hospital, Kahramanmaras, 2 Department of Cardiology, Kayseri Education and Research Hospital, and
3
Department of Cardiology, Erciyes University School of Medicine, Kayseri, Turkey.
Address for correspondence: Bahadir Sarli, MD, Department of Cardiology, Kayseri Education and Research Hospital, 38010, Kayseri, Turkey. E-mail: drsarli@yahoo.
com
Received for publication June 3, 2014. Revised and accepted June 16, 2014.
Released in advance online on J-STAGE December 24, 2014.
All rights reserved by the International Heart Journal Association.
18
Vol 56
No 1 NLR AND SYNTX SCORE IN NSTEMI
Biochemical analysis: Fasting blood samples (12 hours) were
collected on the day of admission to the hospital. All measure-
ments were performed within 30 minutes after blood collec-
tion. Complete blood count (Cell-Dyn 3700 System; Abbot,
Abbott Park, Illinois), fasting blood glucose, creatinine levels,
and lipid profile were analyzed for all patients using a Beck-
man-Coulter AU 2700 (Australia Pty Ltd, Sydney, Australia).
High-sensitivity C-reactive protein (hsCRP) level was analyzed
using a BN-II nephelometer (Siemens, Marburg, Germany).
Coronary angiography: Quantitative coronary angiography
was performed using the Judkins technique by 2 experienced
interventional cardiologists unaware of the clinic and laborato-
ry results of the patients. Significant CAD was defined as >
50% stenosis in at least 1 coronary artery. Each coronary le-
sion producing a ≥ 50% luminal obstruction in vessels ≥ 1.5
mm was separately scored and added to provide the vessel SX-
score. The SXscore was calculated using dedicated software
that integrates the number of lesions with their specific weight-
ing factors based on the amount of myocardium distal to the
lesion according to the score of Leaman, et al and the morpho-
logic features of each single lesion, as previously reported.13,14)
The study population was then divided into 3 tertiles based on
the SYNTAX trial results.1) The low syntax group (n = 329)
was defined as those with a SXscore ≤ 22, the intermediate
syntax group (n = 58) as a SXscore ≥ 23 and < 33, and the high
syntax group (n = 27) as those with an SXscore ≥ 33. An in-
hospital major adverse cardiac event (MACE) was defined as a
non-fatal MI, in-stent thrombosis, or in-hospital mortality dur-
ing hospitalization.
Statistical analysis: Statistical analysis was performed using
the SPSS software version 15 (SPSS Inc., Chicago, Illinois,
USA). Continuous variables are presented as the mean ±
standard deviation and categorical variables as a percentage.
The variables were investigated using the Kolmogorov-Smir-
nov test to determine whether or not they were normally dis-
tributed. Continuous variables were compared using 1-way
analysis of variance and the post hoc Tukey test. The chi-
square test was used for univariate analysis of the categorical
variables. Linear regression analysis was performed to identify
the significance of the relation between the SXscore and sever-
al variables. The effects of different variables on in-hospital
MACE were calculated using univariate analyses for each vari-
able. The variables for which the unadjusted P value was less
than 0.10 in logistic regression analysis were identified as po-
tential risk markers and included in the full model. We reduced
the model using backward elimination multivariate logistic re-
gression analyses, and we eliminated potential risk markers us-
ing likelihood ratio tests. A 2-tailed P < 0.05 was considered
Table I. Independent Correlates of Variables With SYNTAX Score in Linear Regression Analysis
Coefficients β
Age (years) 0.222
Diabetes 0.048
Hypertension -0.060
Smoking 0.082
NLR 0.380
Mean platelet volume 0.044
LDL 0.104
C-reactive protein 0.067
LDL indicates low density lipoprotein cholesterol; and NLR, neutrophil to lymphocyte ratio.
19
significant.
Results
The clinical characteristics and laboratory parameters of
the patients with NSTEMI and controls are listed in Supple-
mental Table I. Left ventricular ejection fraction (49 ± 8% to
61 ± 3.5%, P < 0.001) was significantly lower in patients with
NSTEMI compared with controls. Also NLR (4.1 ± 3.9 to 2 ±
0.8, P = 0.002), mean platelet volume (MPV, 9.3 ± 1.3fl to 8.2
± 1.8, P < 0.001), and C-reactive protein (CRP, 21 ± 29 mg/L
to 5.5 ± 4 mg/L, P = 0.002) were significantly higher in pa-
tients with NSTEMI.
Patients with a low SXscore were younger (62.2 ± 12
years to 69.6 ± 9 years and 69.9 ± 11 years, P < 0.001), had
lower triglyceride levels (176 ± 88 mg/dL to, 210 ± 123 mg/
dL, and 214 ± 128 mg/dL, P = 0.013) and lower CRP levels
(18 ± 26 mg/L to 29 ± 36 mg/L and 34 ± 36 mg/L, P = 0.003)
compared to patients with an intermediate or high SXscore.
Also, MPV was lower in patients with a low SXscore com-
pared to patients with an intermediate SXscore (9.1 ± 1.3 fl to
9.6 ± 1.4 fl, P = 0.032) in post-hoc analysis. NLR was signifi-
cantly lower in patients with a low SXscore compared to pa-
tients with an intermediate or high SXscore (3.7 ± 4 to 4.6 ± 2
and 7.9 ± 4, P < 0.001, Supplemental Figure 1, Supplemental
Table II). In addition, when the patients were divided into 3
tertiles according to NLR values, patients with the highest
NLR tertile had significantly higher peak CK-MB when com-
pared with patients with the lowest and intermediate NLR ter-
tiles (75 ± 12 to 55 ± 6 and 47 ± 13, P < 0.001, respectively).
Linear regression analysis revealed that NLR (coefficient
β = 0.380, 95%CI: 1.165-1.917, P < 0.001), age (coefficientβ
= 0.222, 95%CI: 0.100-0.245, P < 0.001) and LDL cholesterol
level (coefficientβ = 0.104, 95%CI: 0.004-0.052, P = 0.024,
Table I) were significantly associated with SXscore in patients
with NSTEMI. Supplemental Figure 2 shows the association
between NLR and SXscore. Multivariate logistic regression
analysis revealed age, SXscore, and NLR were independent
predictors of in-hospital MACE in patients with NSTEMI (Ta-
ble II).
Discussion
Our results clearly demonstrate that patients with NSTE-
MI had higher NLR compared to controls with normal coro-
nary arteries. Our results also show that there is a significant
95% CI P
0.100-0.245 < 0.001
-0.950-2.949 0.312
-3.065-0.697 0.214
-0.290-3.448 0.093
1.165-1.917 < 0.001
-0.314-0.913 0.332
0.004-0.052 0.024
-0.008-0.052 0.156

20 KURTUL, ET AL
Table II. Effects of Multiple Variables on In-Hospital MACE in Univariate and Multivariate Logistic Regression Analysis
Variable Unadjusted OR 95% CI
Age 1.058 1.022 - 1.094
Diabetes 1.213 0.553 - 2.659
Hypertension 1.018 0.474 - 2.188
Smoking 1.586 0.762 - 3.303
NLR 1.601 1.385 - 1.851
MPV 1.010 0.774 - 1.318
SX score 1.159 1.111 - 1.210
Adjusted for age, NLR, SXscore. MPV indicates mean platelet volume; NLR, neutrophil to lymphocyte ratio; and SXscore, SYN-
TAX score.
association between NLR and severity of CAD in patients with
NSTEMI. In this study we showed that patients with a high
SXscore had higher NLR compared to those with a low or in-
termediate SXscore in NSTEMI.
Non-ST segment elevation myocardial infarction is one
of the most frequent presentations of patients with CAD. Al-
though in-hospital mortality in patients with NSTEMI is lower
than those with ST segment elevation, 6-month mortality is
similar. Moreover, 4-year mortality in patients with NSTEMI
is two-fold higher than patients with ST segment myocardial
infarction.3,4,15) Therefore, risk stratification, management of
patients with NSTEMI in the acute phase, and long-term fol-
low-up are crucial to prevent increased mortality and morbidity
in these patients.
The SXscore, a lesion-based angiographic scoring sys-
tem, has been introduced to grade the complexity of coronary
artery disease. Since the initial trial, several trials have demon-
strated that the SXscore can be used to risk-stratify patients
with complex coronary disease. These studies have shown that
patients with a relatively high SXscore have worse cardiovas-
cular outcomes, and that the score is an independent predictor
of MACE for percutaneous coronary intervention (PCI).16-18)
Therefore, SXscore can be used in the selection of optimal
treatment by identifying those patients at highest risk of ad-
verse events following PCI.
The role of inflammation in the initiation and progression
of coronary atherosclerosis is well described.7,9,10) High levels
of inflammatory markers have been found in association with
the severity of coronary atherosclerosis, prognosis in acute
coronary syndromes, and prognosis after coronary interven-
tions.12)
NLR has been proposed as a prognostic marker and
shown to be related with a pro-inflammatory state and resultant
worse clinical outcomes in cardiovascular disease. NLR has
been evaluated as a prognostic marker for several cardiovascu-
lar diseases including coronary artery ectasia, stable CAD,
NSTEMI, and STEMI.7,19-21) NLR has also been shown in as-
sociation with complexity of CAD in patients with stable CAD
and acute coronary syndromes. In a recent study, Sahin, et al
showed that NLR was significantly associated with severity of
CAD in patients with STEMI. They also showed that NLR
was an independent predictor for SXscore in patients with
STEMI.22) Another study conducted by Kaya, et al showed that
NLR was significantly associated with both the presence and
severity of CAD in patients with stable CAD.23) In a more re-
cent study, Altun, et al. showed that in patients with acute cor-
onary syndrome, high sensitive troponin T and NLR were sig-
nificantly correlated with the severity of CAD.
Int Heart J
January 2015
P Adjusted OR 95% CI P
< 0.001 1.053 1.010 - 1.099 0.016
0.631
0.964
0.218
< 0.001 1.436 1.218 - 1.692 < 0.001
0.941
< 0.001 1.062 1.020 - 1.105 0.003
Similar to previous investigations, our study demonstrates
that NLR, an indicator of systemic inflammatory response, is
significantly associated with severity of CAD and may predict
the SXscore in patients with NSTEMI. To our knowledge the
present study is the largest study investigating the role of NLR
on SXscore in patients with NSTEMI. The role of inflamma-
tion in the initiation and progression of atherosclerosis is well
established. During the early stages of atherosclerotic plaque
development, inflammatory monocytes are provoked to move
into the vascular wall by several adhesion and chemoattractant
molecules released from endothelial cells.24) These monocytes
differentiate to macrophages to contribute to the formation of
the lipid core in advanced stages of atherosclerotic plaque de-
velopment. In mature atherosclerotic plaque, various inflam-
matory mediators play a role in the expression of proteolytic
enzymes which may weaken the fibrous cap and result in
plaque rupture.25,26) With this background in mind, we suggest
that the inflammatory state, represented by NLR, contributes to
the formation of coronary atherosclerosis in patients with
NSTEMI.
Our study has several limitations. First, this is an observa-
tional, single-institution, cross-sectional study. However, our
study is the first to evaluate the relation between SXscore and
NLR in homogenous unselected NSTEMI patients, therefore
mirroring a real world scenario. Second, additional markers of
inflammation were not assessed in our study. Also, the lack of
longitudinal data regarding the association of NLR and prog-
nosis of NSTEMI is another limitation of the study.
In conclusion, NLR is a widely available parameter
around the world. In patients with NSTEMI, NLR was higher
in the high-SXscore group than in the low-SXscore group and
was independently associated with SXscore. Also, there was a
significant correlation between the SXscore and NLR ratio.
Thus, we suggest that patients with NSTEMI who have more
atherosclerotic involvement also have a higher NLR and we
also suggest that a preprocedural NLR, which is an inexpen-
sive and universally available marker, can be used for the risk
stratification of patients with NSTEMI. Additionally, these re-
sults might play an important role in better understanding the
role of inflammation in the pathogenesis of atherosclerosis and
may lead to improved treatment strategies in patients with
NSTEMI.
Disclosure
Conflict of interest: None
Vol 56
No 1 NLR AND SYNTX SCORE IN NSTEMI
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Supplemental Files
Supplemental Table I, II
Supplemental Figure 1, 2
Please find supplemental files;
  https://www.jstage.jst.go.jp/article/ihj/56/1/56_14-175/_article/supplement