Original research 1
Relationship between C-reactive protein-to-albumin ratio and
the extent of coronary artery disease in patients with
non-ST-elevated myocardial infarction
Muhsin Kalyoncuoglu and Gunduz Durmus
Background This study aimed to investigate the predictive
value of the newly defined C-reactive protein (CRP)-to-
albumin ratio (CAR) in determining the extent and severity
of coronary artery disease (CAD) in comparison with the
other inflammatory markers such as neutrophil-to-
lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio
(PLR), in patients with non-ST-elevated myocardial
infarction (NSTEMI).
Patients and methods This study is retrospectively
designed and includes 205 patients with NSTEMI with a
mean age of 56.6 ± 11.4 years. The study cohort was
subdivided into two groups according to Synergy Between
Percutaneous Coronary Intervention with Taxus and cardiac
surgery score (SS) as low (< 23) and intermediate-high
(≥23). Complete blood counts, serum CRP, and serum
albumin were obtained at admission. The CAR, NLR, and
PLR values of all patients were calculated. Then, we
evaluated the relationship of CAR, NLR, and PLR with the
CAD extent and severity.
Results CAR and NLR were moderately correlated with SS
(r = 0.517, P < 0.001; r = 0.222, P = 0.001, respectively),
whereas PLR showed weak correlation with SS (r = 0.191,
P = 0.006). According to multivariate analysis models, CAR,
Introduction
Inflammation plays an essential role in the progression and
destabilization of atherosclerosis and eventually in the
initiation of acute coronary syndrome (ACS) by leading to
vascular inflammation, plaque rupture, and subsequent
thrombosis [1–3]. Several inflammatory markers such as
neutrophil-to-lymphocyte ratio (NLR) and platelet-to-
lymphocyte ratio (PLR) are associated with coronary artery
disease (CAD) severity and worse cardiovascular outcomes
[4–6]. Recent studies have also reported that acute-phase
proteins (APPs) such as C-reactive protein (CRP) and albu-
min are associated with the presence of both stable and
unstable CAD, CAD severity, peripheral artery disease,
stroke, and unfavourable cardiovascular outcomes [2,3,7].
The serum levels of APPs vary according to the severity of the
cardiovascular disease [2]. Recently, a novel parameter
defined as the ratio of C-reactive protein–to-albumin (CAR)
has been proposed as more valuable than either CRP or
albumin alone in predicting inflammatory status and prognosis
in various clinical settings [8–10]. To the best of our knowl-
edge, very few data exist regarding the association between
0954-6928 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
NLR, and left ventricular ejection fraction were found to be
independent predictors of CAD severity (P < 0.05). The area
under the curve (AUC) for CAR (AUC: 0.829; 95% confidence
interval: 0.770–0.878) was significantly greater than the AUC
of NLR (AUC: 0.657; 95% confidence interval: 0.588–0.722),
with P value of 0.002. A CAR more than 17 predicted an
intermediate-high SS with 86% sensitivity and 76%
specificity.
Conclusion Novel inflammatory marker CAR can be used
as a reliable marker in prediction of CAD severity in patients
with NSTEMI. Coron Artery Dis 00:000–000 Copyright ©
2019 Wolters Kluwer Health, Inc. All rights reserved.
Coronary Artery Disease 2019, 00:000–000
Keywords: coronary artery disease, C-reactive protein, lymphocytes,
neutrophils, serum albumin
Cardiology Department, Haseki Training and Research Hospital, University of
Health Sciences, Istanbul, Turkey
Correspondence to Muhsin Kalyoncuoglu, MD, Cardiology Department, Haseki
Training and Research Hospital, University of Health Sciences, 34107 Istanbul,
Turkey
Tel: + 90 537 598 1051; fax: + 90 212 589 6229;
e-mail: mkalyoncuoglu80@gmail.com
Received 4 May 2019 Revised 18 May 2019 Accepted 29 May 2019
CAR and the CAD severity [7,11]. Additionally, there is no
comparative study on the use of CAR and inflammatory
markers for the prediction of CAD severity in patients with
non–ST-elevated myocardial infarction (NSTEMI). As such,
in this study, aimed to investigate the relationship between
CAR and CAD severity, as identified by the Synergy
Between Percutaneous Coronary Intervention with Taxus
and cardiac surgery (SYNTAX) score (SS), in comparison with
NLR and PLR.
Patients and methods
Study population
We reviewed the medical records of consecutive patients
from January 2015 to December 2017 who were admitted to
the Department of Cardiology, Haseki Training and
Research Hospital, University of Health Sciences in
Istanbul, Turkey. Patients who were diagnosed with
NSTEMI and who underwent coronary angiography with or
without percutaneous coronary intervention (PCI) were
enrolled in our study. Based on hospital records, patient
baseline clinical and demographic characteristics including
DOI: 10.1097/MCA.0000000000000768
 2 Coronary Artery Disease 2019, Vol 00 No 00
hypertension, diabetes mellitus, CAD, family history of
CAD, dyslipidemia, smoking, chronic obstructive pulmon-
ary disease, and history of CAD or a CAD-equivalent con-
dition such as peripheral arterial disease were obtained.
Peripheral arterial disease was defined as either the presence
of atherosclerotic disease in the aorta and arteries other than
the coronary arteries with exercise-related claudication, the
use of revascularization therapies, reduced or absent pulsa-
tion, or angiographic stenosis of more than 50%.
The medical records of 321 patients were retrospectively
reviewed and analyzed by using our database. Finally, 205
patients were enrolled in the study. Patients with a history
of CAD treated with PCI or coronary artery bypass grafting
(n = 36), malignancy (n = 12), active infection (n = 15),
connective tissue disorder (n = 5), end-stage renal disease
or receiving haemodialysis (n = 16), no significant CAD or
other evident causes of coronary pain such as significant
myocardial bridging or diffuse coronary spasm during
angiography (n = 24), and/or any missing information
(n = 7) were excluded from the study.
The diagnosis of ACS is made according to symptoms,
ECG findings, and other accessory examinations, and the
standard of ACS diagnosis employs diagnostic criteria of
ACS from the American College of Cardiology/American
Heart Association guidelines. Presentation with acute
chest pain or overwhelming shortness of breath with the
absence of persistent ST-elevation is suggestive of non-
ST-elevated ACS (except in patients with true posterior
myocardial infarction). Non-ST-elevated-ACS can be
further subdivided based on cardiac biomarkers of
necrosis such as cardiac troponin. If cardiac biomarkers
are elevated and the clinical findings are appropriate, the
patient is considered to have NSTEMI; otherwise, the
patient is deemed to have unstable angina pectoris [12].
To identify the patient’s risk, Global Registry for Acute
Coronary Events risk score (GRS) was also calculated
from the medical history, initial clinical findings, ECG,
and laboratory values collected on admission. The GRS
system consists of the following eight variables recorded
at admission: age, heart rate, systolic blood pressure,
plasma creatinine, Killip class, ST-segment deviation,
elevated cardiac biomarkers, and cardiac arrest at the time
of admission. The final score can range from 0 to 372
points [13]. All patients were treated in accordance with
the current guidelines [12,14]. As our study was retro-
spectively designed, written informed consent from par-
ticipants could not be obtained, but our study protocol
was approved by the ethics committee of the Haseki
Training and Research Hospital.
Laboratory measurements
In our hospital, blood samples were collected from the
antecubital vein within 24 h of hospital admission.
Complete blood cell counts including total white blood
cells (WBCs), haemoglobin, platelets, neutrophils, lym-
phocytes, and monocytes were all measured with an
Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
autoanalyzer. Plasma levels of fasting blood glucose, total
cholesterol, triglycerides, high-density lipoprotein cho-
lesterol, low-density lipoprotein cholesterol, creatinine,
and troponin I levels were measured for all patients by
using an automated chemistry analyzer. Serum albumin
and CRP levels were measured by using a Roche
Diagnostics Cobas 8000 c502 analyser (Roche Holding
AG, Basel, Switzerland).
CAR was calculated as the ratio of serum CRP level (mg/
l) to serum albumin level (g/l) multiplied by 100 for easy
interpretation, as done in previous studies [7,9]. NLR
was calculated by dividing the neutrophil count with the
lymphocyte count [4,6]. PLR was calculated as the ratio
of the platelet count to lymphocyte count [5]. The esti-
mated glomerular filtration rate was calculated by using
the Modification of Diet in Renal Disease formula. Left
ventricular ejection fraction (LVEF) was measured by
using the modified Simpson method in the apical four-
chamber and two-chamber views in both end-diastole
and end-systole.
Angiographic analyses
Coronary angiograms were recorded to digital media for
quantitative analysis (DICOM viewer; MedCom GmbH,
Darmstadt, Germany). Coronary angiograms were ana-
lyzed by two experienced interventional cardiologists
who were blinded to patients’ clinical data.
The anatomic severity of coronary stenosis was quanti-
tatively evaluated with the anatomical SS by using the
version downloaded from http://www.syntaxscore.com.
The study population was divided into two groups as
follows according to CAD severity by using SS: low
(< 23) and intermediate-high (≥23).
Statistical analysis
Statistical analyses were performed using the statistical
package for the social sciences version 24.0 software program
(IBM Corp., Armonk, New York, USA). The continuous
variables were given as mean ± SD (if normal distribution)
and medians (interquartile ranges) (if not normal distribu-
tion). The categorical variables were given as percentages.
The χ2-test was used to compare the categorical variables
between the groups. The Kolmogorov–Smirnov test was
used to assess whether the variables were normally dis-
tributed. The Student’s t-test or Mann–Whitney U-test was
used to compare the continuous variables between the
groups according to whether they were normally distributed
or not. Pearson’s coefficient was calculated to describe the
degree of correlation of parameters among each other and
with SS. To identify the independent predictors of an
intermediate-high SS score, univariate and multivariate
logistic regression analyses were performed. Only the vari-
ables with a P value of less than 0.1 in univariate analysis
were incorporated in the multivariate logistic regression
analysis. Receiver operating characteristic (ROC) curve
 Relationship between CAR and CAD severity Kalyoncuoglu and Durmus 3

analysis was performed to determine additional abilities of
parameters found to be independent predictors of
intermediate-high SS. The optimal cutoff value was calcu-
lated from the point of maximal sensitivity and specificity
(Youden’s index). To compare the predictive performance
of parameters found to be independent predictors of
intermediate-high SS, DeLong test was also used. The
results were evaluated within a 95% confidence interval (CI)
and at a significance level of P value less than 0.05.
Results
The study population included 205 patients with NSTEMI
with a mean age of 56.6 ± 11.4 years. Of these, 168 (82%)
were male and 108 (52.7%) had HT, 53 (25.9%) had DM,
63 (30.7%) had dyslipidemia, and 122 (59.5%) were smo-
kers. The mean SS value of the study population was
15.2 ± 9.9, and 58 (28%) patients had intermediate-high SS.
Of the study participants, the mean CAR value was
22 ± 18.5, mean NLR value was 3.2 ± 2.3, and mean PLR
value was 106.1 ± 56.4. Detailed demographic, clinical,
angiographic, and laboratory parameters of the study cohort
are represented in Tables 1 and 2.
Independent predictors of intermediate-high Synergy
Between Percutaneous Coronary Intervention with Taxus
and cardiac surgery score
Intermediate-high SS patients were older (P = 0.02) and
had higher GRSs and lower LVEF values as compared
with low SS patients (P = 0.001 and P < 0.001, respec-
tively). According to admission laboratory results, serum
creatinine level (P = 0.05), serum CRP level (P < 0.001),
and neutrophil (P = 0.001) and monocyte (P = 0.008)
counts were higher in the intermediate-high SS group,
but serum albumin level was lower (P = 0.01). As com-
pared with patients in the low SS group, patients in the
intermediate-high SS group also had significantly higher
values of CAR (P < 0.001), NLR (P = 0.007), and PLR
(P = 0.02).
Correlation analysis revealed that CAR and NLR exhibited
moderate correlation with SS (r = 0.517, P < 0.001 and
r = 0.222, P = 0.001, respectively), whereas PLR was weakly
correlated with SS (r = 0.191, P = 0.006). Additionally, CAR,
NLR, and PLR were moderately correlated with GRS
(r = 203, P = 0.003; r = 0.212, P = 0.002; and r = 0.245,
P < 0.001, respectively). Besides that, we also observed a good
positive correlation between NLR and PLR (r = 0.756,
P < 0.001). Detailed correlation analysis findings are depicted
in scatterplot diagrams (Fig. 1).
To determine the independent predictors of intermediate-
high SS, we performed multivariable logistic regression
analysis by using variables that showed statistically sig-
nificant associations in the univariate analysis, except the
angiographic parameters. CRP and age were not included in
the regression analysis because of excellent correlation
between CAR and CRP (r = 0.962, P < 0.001) and between
GRS and age (r = 0.825, P < 0.001), but albumin was inclu-
ded as it exhibited a relatively weak correlation with CAR
(r = − 0.283, P < 0.001). As we found a perfect correlation
between NLR and PLR, we developed two separate mul-
tivariate analysis models that included NLR (model 1) and
PLR (model 2) separately (Table 3). Model 1 multivariate
analysis demonstrated that higher CAR values [odds ratio
(OR): 1.071; 95% CI: 1.045–1.097; P < 0.001], higher NLR
values (OR: 1.186; 95% CI: 1.015–1.387; P = 0.032), and
lower LVEF values (OR: 0.950; 95% CI: 0.908–0.994;

Table 1 Demographic, clinical, and angiographic parameters of study population grouped by Synergy Between Percutaneous Coronary
Intervention with Taxus and cardiac surgery score
Variables All population ≤ 22 (n = 147) ≥ 23 (n = 58) P

Clinical characteristics
Sex (male) [n (%)] 168 (82) 123 (82.6) 45 (80.4) 0.71
Age (years) 56.6 ± 11.4 55.5 ± 10.9 59.8 ± 12.3 0.02
BMI (kg/m2) 26.7 ± 3.0 26.7 ± 3.1 26.7 ± 2.8 0.92
Hypertension [n (%)] 108 (52.7) 76 (51.4) 32 (56.1) 0.54
Diabetes mellitus [n (%)] 53 (25.9) 38 (25.7) 15 (26.3) 0.93
Dyslipidemia [n (%)] 63 (30.7) 41 (27.7) 22 (38.6) 0.13
Smoking [n (%)] 122 (59.5) 88 (59.1) 34 (60.7) 0.83
Family history [n (%)] 123 (60) 89 (59.7) 34 (60.7) 0.89
CAD history [n (%)] 56 (27.3) 41 (27.7) 15 (26.3) 0.84
LVEF (%) 49.8 ± 8.1 51.3 ± 8.0 45.9 ± 6.9 < 0.001
GRS 95.2 ± 24.8 91.8 ± 23.7 103.9 ± 25.6 0.001
In-hospital mortality [n (%)] 7 (3.4) 3 (2.1) 4 (6.3) 0.13
Angiographic characteristics
LMCA disease [n (%)] 18 (8.8) 1 (0.7) 17 (29.7) < 0.001
TVD [n (%)] [n (%)] 38 (18.5) 10 (6.8) 28 (49.1) < 0.001
Bifurcation [n (%)] 38 (18.5) 11 (7.4) 27 (47.4) < 0.001
CTO [n (%)] 48 (23.4) 13 (8.8) 35 (61.4) < 0.001
Lesion length > 20 mm [n (%)] 52 (25.4) 17 (11.5) 35 (61.4) < 0.001
Severe tortuosity [n (%)] 38 (18.5) 16 (10.8) 22 (38.6) < 0.001
Heavy calcification [n (%)] 41 (20) 19 (12.8) 22 (38.6) < 0.001
Thrombus [n (%)] 60 (29.3) 31 (20.9) 29 (50.9) < 0.001
SS 15.2 ± 9.9 10 ± 5.1 28.3 ± 6.2 < 0.001

CAD, coronary artery disease; CTO, chronic total occlusion; GRS, Global Registry for Acute Coronary Events risk score; LMCA, left main coronary artery; LVEF, left
ventricular ejection fraction; SS, Synergy Between Percutaneous Coronary Intervention with Taxus and cardiac surgery score; TVD, three-vessel disease.

Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 4 Coronary Artery Disease 2019, Vol 00 No 00

Table 2 Laboratory parameters of study population grouped by P = 0.028) were statistically independent predictors for
Synergy Between Percutaneous Coronary Intervention with Taxus
and cardiac surgery score intermediate-high SS. Elsewhere, model 2 multivariate
analysis revealed that higher CAR value (OR: 1.069; 95%
≤ 22 (n = 147) ≥ 23 (n = 58)
Variables All population P
CI: 1.044–1.095; P < 0.001) and lower LVEF value (OR:
FBG (mg/dl) 141 ± 61.4 140.8 ± 60.9 150.4 ± 70.2 0.33 0.949; 95% CI: 0.907–0.993; P =0.023) predicted CAD
Creatinine (mg/dl) 0.89 ± 0.26 0.87 ± 0.23 0.95 ± 0.31 0.05 severity. To determine the additional abilities of CAR and
TC (mg/dl) 205.6 ± 51 203.1 ± 49.8 212.1 ± 52.7 0.27
LDL-C (mg/dl) 129.6 ± 40.8 128.6 ± 38 132 ± 47.5 0.58 NLR in the prediction of CAD severity, we performed a
HDL-C (mg/dl) 38.7 ± 9.2 38.4 ± 8.8 39.7 ± 10.3 0.38 ROC analysis and determined a cutoff value for CAR of 17
Triglycerides 209.1 ± 147.6 210.7 ± 143.7 205.2 ± 157.8 0.80
(mg/dl)
(86% sensitivity and 76% specificity) and that for NLR of
Neutrophil 6.7 ± 2.7 6.3 ± 2.4 7.7 ± 2.9 0.001 2.3 (72% sensitivity and 51% specificity) as defined by
(103/μl) Youden’s index (i.e. the point at which the values of sen-
Lymphocyte 2.5 ± 0.9 2.6. ± 0.9 2.4 ± 1.0 0.22
(103/μl)
sitivity and specificity were maximal). When we compared
Platelet (103/μl) 236.2 ± 69.5 234.8 ± 72.9 239.7 ± 60.4 0.65 the ROC curves of CAR, and NLR, the area under the
Monocyte (103/μl) 0.69 ± 0.3 0.66 ± 0.29 0.78 ± 0.32 0.008 curve (AUC) value of CAR (AUC: 0.829; 95% CI:
CRP (mg/l) 8.2 ± 6.8 5.9 ± 4.5 14.1 ± 7.8 < 0.001
Albumin (g/l) 38.8 ± 3.7 39.2 ± 3.6 37.7 ± 3.8 0.01 0.770–0.878; P < 0.001) was significantly different from that
CAR (×100) 22 ± 18.5 15.8 ± 13.3 37.8 ± 20.5 < 0.001 of NLR (AUC: 0.657; 95% CI: 0.588–0.722; P < 0.001), with
3.2 ± 2.3 2.9 ± 2.1 3.8 ± 2.5
NLR
PLR 106.1 ± 56.4 100.9 ± 49 120.0 ± 70
0.007
0.02
a P value of 0.002 (Fig. 2).

CAR, C-reactive protein-to-albumin ratio; CRP, C-reactive protein; FBG, fasting Discussion
blood glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density
lipoprotein cholesterol; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to- The main findings of this study are as follows: (i) ele-
lymphocyte ratio; TC, total cholesterol. vated CAR, higher NLR, and lower LVEF values are

Fig. 1

Correlation analysis of inflammatory markers and GRS with the SS. CAR, C-reactive protein to albumin ratio; GRS, Global Registry for Acute
Coronary Events risk score; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; SS, Synergy Between Percutaneous Coronary
Intervention with Taxus and cardiac surgery score.

Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 Relationship between CAR and CAD severity Kalyoncuoglu and Durmus 5

Table 3 Factors that were found to be independently associated with the intermediate-high Synergy Between Percutaneous Coronary
Intervention with Taxus and cardiac surgery score in univariate and multivariate logistic regression analysis models (model 1 and model 2)
Univariate Model 1 multivariate Model 2 multivariate

Variables OR (95% CI) P OR (95% CI) P OR (95% CI) P

CAR 1.075 (1.051–1.099) < 0.001 1.071 (1.045–1.097) < 0.001 1.069 (1.044–1.095) < 0.001
NLR 1.185 (1.041–1.348) 0.01 1.186 (1.015–1.387) 0.032 – –
PLR 1.006 (1.001–1.011) 0.025 – – 1.004 (0.998–0.1.011) 0.21
GRS 1.020 (1.007–1.034) 0.002 1.005 (0.988–1.023) 0.56 1.006 (0.988–1.024) 0.51
LVEF 0.916 (0.877–0.958) < 0.001 0.950 (0.908–0.994) 0.028 0.949 (0.907–0.993) 0.023
Albumin 0.895 (0.822–0.975) 0.01 0.956 (0.863–1.060) 0.39 0.968 (0.876–1.071) 0.53
Creatinine 3.132 (0.991–9.902) 0.05 2.303 (0.592–8.966) 0.22 2.242 (0.580–8.661) 0.24

CAR, C-reactive protein-to-albumin ratio; CI, confidence interval; GRS, Global Registry for Acute Coronary Events risk score; LVEF, left ventricular ejection fraction; NLR,
neutrophil-to-lymphocyte ratio; OR, odds ratio; PLR, platelet-to-lymphocyte ratio.

Fig. 2 severity and adverse cardiovascular outcomes [4–6]. In the

Receiver operating characteristic (ROC) curves of the C-reactive
protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR)
for prediction the intermediate-high Synergy Between Percutaneous
Coronary Intervention with Taxus and cardiac surgery score. CI,
confidence interval.
significantly associated with CAD severity as identified
by using the SS in patients with NSTEMI; (ii) a CAR
value of more than 17 and a NLR value of more than 2.3
were found to be predictors of intermediate-high SS; and
(iii) CAR is a superior marker to NLR for the prediction
of CAD extent and severity in patients with NSTEMI.
It is well known that inflammation plays a very important
role in atherosclerosis and that the burden of coronary
atherosclerosis is closely associated with the prognosis in
ACS [1–3,15].
There is substantial evidence to suggest that inflammation is
involved in all stages of coronary atherosclerosis, and high-
circulating platelet count and WBC counts including neu-
trophils, lymphocytes, and monocytes are associated with
major adverse cardiovascular outcomes [16–18]. According to
the literature, various inflammatory markers such as NLR
and PLR have been proposed to be related with CAD
current study, we demonstrated that NLR is a predictor
marker for CAD severity but that PLR is not. Parallel to us,
Sari et al. [6] also reported that, of all other systemic
inflammatory markers including PLR, only NLR is an
independent predictor of CAD severity. Although total
WBC count was found to be associated with the presence,
severity, and extent of coronary atherosclerosis and with
increased mortality and worse outcomes after acute myo-
cardial infarction, NLR was proposed to be more accurate
and stable than absolute blood cell counts, especially in
patients with acute presentations [4]. NLR is calculated by
taking the absolute neutrophil count and dividing it by the
absolute lymphocyte count. It demonstrates the balance of
the neutrophils, which constitute an active inflammatory
component, and the lymphocytes, which are the regulatory
and protective components [4]. Indeed, leukocytes play an
important role in inflammatory processes and neutrophils are
the most abundant type of WBC [4]. The main role of
neutrophil in CAD may be explained by the secretion of
various inflammatory mediators such as elastase, myeloper-
oxidase, and free oxygen radicals, which cause tissue
damage. The probable cause of lymphopenia may be linked
to increased steroid levels owing to CAD-induced stress and
increased apoptosis triggered by increased inflammation,
which thereby results in elevated NLR [19]. As a result, a
higher NLR represents a higher level of inflammation, and
this may explain why NLR was found to be related with
CAD extent and severity.
The inflammatory status can be measured by using APPs
such as CRP (a positive APP) and albumin (a negative APP)
[2,3]. CRP is one of the major APPs that may not only be a
marker of systemic inflammation but also a component that
directly and actively participates in both atherogenesis and
atheromatous plaque disruption [2,20]. In the literature,
increased CRP levels have been reported to be indepen-
dently associated with the extent of CAD and recurrent
cardiovascular events in patients with stable CAD and ACS
[21,22]. Although the pathophysiological mechanisms are
not fully understood, it is most likely that CRP has a role in
all phases of atherosclerosis by directly influencing pro-
cesses such as endothelial damage, complement activation,

Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 6 Coronary Artery Disease 2019, Vol 00 No 00
apoptosis, vascular cell activation, and thrombosis [20].
There is also substantial evidence that decreased albumin
plasma concentrations may be causally related to athero-
sclerosis development and progression [23]. The potential
pathophysiological mechanism of hypoalbuminemia in
CAD may be primarily related to its decreased antioxidant,
anti-inflammatory, and antiplatelet aggregation activity
leading to impaired endothelial function, increased blood
viscosity, oxidative stress, and increase of an important
mediator of platelet-derived coronary artery narrowing
[3,24]. Besides that, it has been suggested that, as a novel
inflammatory parameter, CAR is more sensitive and specific
in the prediction of the systemic inflammatory state and
prognosis in various noncardiac clinical conditions when
compared with the predictive values of these two markers
separately [8–10]. CAR first was described by Fairclough
et al. [8] and proposed as a better prognostic parameter to
predict poor prognosis than either serum CRP or albumin
levels alone in patients with acute medical conditions.
Similar to in our study, Cagdas et al. [7] demonstrated that
CAR predicted CAD severity as defined by SS. These
authors also reported that CAR was a more valuable marker
than CRP and albumin in the prediction of intermediate-
high SS in patients with NSTEMI. Moreover, some pre-
vious studies have shown that CAR is superior to NLR in
predicting the systemic inflammatory response syndrome
and prognosis in various noncardiac conditions [25–28].
Recently, Cınar et al. [29] also proposed that CAR has better
prognostic performance for predicting poor prognosis in
patients with STEMI in comparison with NLR. There is
no study published to date comparing the predictive value
of CAR and other inflammatory markers such as NLR and
PLR. As such, this research is the first study to evaluate the
value of CAR in predicting CAD versus NLR and PLR. In
this study, although NLR independently predicted CAD
severity, CAR exhibited better predictive performance for
intermediate-high SS than did NLR.
Here, we also observed that GRS was not associated with
CAD severity in both multivariant analysis models. We
know that GRS is not intended to predict the severity of
CAD, and the current data evaluating the association
between GRS and CAD severity are still controversial
[30,31]. Additionally, in this study, LVEF was found to
be an independent predictor for CAD extent and sever-
ity, as also indicated in previous studies [32].
Importantly, this study has some limitations. First, this
study employed a retrospective design, had a relatively
small sample size, and relied on single-centre experience.
Second, coronary artery severity based on luminal ste-
nosis was only evaluated by visual coronary angiograms
and we did not include additional information about the
quantitative assessment of coronary artery atherosclerosis
such as distribution, lumen area, plaque burden, and
characteristics. Third, this study also did not include
patients with a history of coronary artery bypass grafting
and PCI. Fourth, we measured only baseline CRP and
Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
albumin levels at admission, and the changes that would
be observed by serial measurements may have an addi-
tional predictive value. Fifth, the data obtained did not
allow us to evaluate the prognostic value of CAR on
adverse cardiovascular outcomes, as we recorded only
small volume and event rate values.
This study demonstrated that decreased LVEF, higher
CAR value, and elevated NLR were independent pre-
dictors for CAD severity. We also observed that the
predictive accuracy of CAR for CAD severity was better
than that of NLR.
Conclusion
This study revealed that CAR has significant association
with SS and may be a potential available, easily mea-
surable, and inexpensive parameter for determining the
coronary atherosclerosis severity. So, it may be a part of
cardiovascular examination to identify individuals with
NSTEMI at high risk for advanced CAD who might
need a more aggressive therapeutic approach and closer
clinical follow-up. However, to evaluate the predictive
value of CAR and especially its prognostic value in
patients with NSTEMI, large-scale and prospective stu-
dies are still required.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
References
1 Wada H, Dohi T, Miyauchi K, Doi S, Naito R, Konishi H, et al. Independent
and combined effects of serum albumin and C-reactive protein on long-term
outcomes of patients undergoing percutaneous coronary intervention. Circ J
2017; 81:1293–1300.
2 Ahmed MS, Jadhav AB, Hassan A, Meng QH. Acute phase reactants as
novel predictors of cardiovascular disease. ISRN Inflamm 2012;
2012:953461.
3 Koenig W, Rosenson RS. Acute-phase reactants and coronary heart
disease. Semin Vasc Med 2002; 2:417–428.
4 Verdoia M, Barbieri L, Di Giovine G, Marino P, Suryapranata H, De Luca G.
Novara Atherosclerosis Study Group (NAS). Neutrophil to lymphocyte ratio
and the extent of coronary artery disease: results from a large cohort study.
Angiology 2016; 67:75–82.
5 Zhou D, Wang G, Fan Y, Wan Z, Liu X. Platelet to lymphocyte ratio is
associated with the severity of coronary artery disease and clinical outcomes
of percutaneous coronary intervention in the Chinese Han population. Exp
Ther Med 2017; 13:731–738.
6 Sari I, Sunbul M, Mammadov C, Durmus E, Bozbay M, Kivrak T, Gerin F.
Relation of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio with
coronary artery disease severity in patients undergoing coronary
angiography. Kardiol Pol 2015; 73:1310–1316.
7 Cagdas M, Rencuzoğullari I, Karakoyun S, Karabag Y, Yesin M, Artaç I, et al.
Assessment of relationship between C-reactive protein to albumin ratio and
coronary artery disease severity in patients with acute coronary syndrome.
Angiology 2017; 70:361–368.
8 Fairclough E, Cairns E, Hamilton J, Kelly C. Evaluation of a modified early
warning system for acute medical admissions and comparison with
C-reactive protein/albumin ratio as a predictor of patient outcome. Clin Med
2009; 9:30–33.
9 Ranzani OT, Zampieri FG, Forte DN, Azevedo LCP, Park M. Creactive
protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One
2013; 8:e59321.
10 Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The
C-reactive protein/ albumin ratio, a novel inflammation-based prognostic
 Relationship between CAR and CAD severity Kalyoncuoglu and Durmus 7
score, predicts outcomes in patients with hepatocellular carcinoma. Ann
Surg Oncol 2015; 22:803–810.
11 Karabag Y, Cagdas M, Rencuzogullari I, Karakoyun S, Artac I, İliş D, et al.
Relationship between C-reactive protein/albumin ratio and coronary artery
disease severity in patients with stable angına pectoris. J Clin Lab Anal
2018; 32:e22457.
12 Amstardam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, et al. 2014
AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation
Acute Coronary Syndromes: A Report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines.
J Am Coll Cardiol 2014; 64:139–228.
13 Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP,
et al. Global Registry of Acute Coronary Events Investigators. Predictors of
hospital mortality in the global registry of acute coronary events. Arch Intern
Med 2003; 163:2345–2353.
14 Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015
ESC Guidelines for the management of acute coronary syndromes in
patients presenting without persistent ST-segment elevation: Task Force for
the Management of Acute Coronary Syndromes in Patients Presenting
without Persistent ST-Segment Elevation of the European Society of
Cardiology (ESC). Eur Heart J 2016; 37:267–315.
15 Palmerini T, Genereux P, Caixeta A, Cristea E, Lansky A, Mehran R, et al.
Prognostic value of the SYNTAX score in patients with acute coronary
syndromes undergoing percutaneous coronary intervention: analysis from
the ACUITY (Acute Catheterization and Urgent Intervention Triage
Strategy) trial. J Am Coll Cardiol 2011; 57:2389–2397.
16 Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol
2012; 32:2045–2051.
17 Nikolsky E, Grines CL, Cox DA, Garcia E, Tcheng JE, Sadeghi M, et al.
Impact of baseline platelet count in patients undergoing primary
percutaneous coronary intervention in acute myocardial infarction (from the
CADILLAC trial). Am J Cardiol 2007; 99:1055–1061.
18 Gaul DS, Stein S, Matter CM. Neutrophils in cardiovascular disease. Eur
Heart J 2017; 38:1702–1704.
19 Sharma K, Patel AK, Shah KH, Konat A. Is neutrophil-to-lymphocyte ratio a
predictor of coronary artery disease in Western Indians? Int J Inflam 2017;
2017:4136126.
20 Shrivastava AK, Singh HV, Raizada A, Singh SK. C-reactive protein,
inflammation and coronary heart disease (review). Egypt Heart J 2015;
67:89–97.
21 Van Wijk DF, Boekholdt SM, Wareham NJ, Ahmadi-Abhari S, Kastelein JJ,
Stroes ES, Khaw KT. C-reactive protein, fatal and nonfatal coronary artery
Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
disease, stroke, and peripheral artery disease in the Prospective EPIC-
Norfolk Cohort Study. Arterioscler Thromb Vasc Biol 2013; 33:2888–2894.
22 Karadeniz M, Duran M, Akyel A, Yarlıoglues M, Ocek AH, Celik IE. High
sensitive CRP level is associated with intermediate and high SYNTAX score
in patients with acute coronary syndrome. Int Heart J 2015; 56:377–380.
23 Schillinger M, Exner M, Mlekusch W, Amighi J, Sabeti S, Schlager O, et al.
Serum albumin predicts cardiac adverse events in patients with advanced
atherosclerosis – interrelation with traditional cardiovascular risk factors.
Thromb Haemost 2004; 91:610–618.
24 Arques S. Human serum albumin in cardiovascular diseases. Eur J Intern
Med 2018; 52:8–12.
25 Xu H, Hu L, Wei X, Niu J, Gao Y, He J, Hou J. The predictive value of
preoperative high-sensitive C-reactive protein/albumin ratio in systemic
inflammatory response syndrome after percutaneous nephrolithotomy.
J Endourol 2019; 33:1–8.
26 Liang Y, Xiao W, Guan YX, Wang W, Chen HY, Fang C, et al. Prognostic
value of the C-reactive protein/albumin ratio (CAR) in patients with operable
soft tissue sarcoma. Oncotarget 2017; 8:98135–98147.
27 Kunizaki M, Tominaga T, Wakata K, Miyazaki T, Matsumoto K, Sumida Y, et al.
Clinical significance of the C-reactive protein-to-albumin ratio for the
prognosis of patients with esophageal squamous cell carcinoma. Mol Clin
Oncol 2018; 8:370–374.
28 Sun P, Chen C, Xia Y, Bi X, Liu P, Zhang F, et al. The ratio of C-reactive
protein/albumin is a novel inflammatory predictor of overall survival in
cisplatin-based treated patients with metastatic nasopharyngeal carcinoma.
Dis Markers 2017; 2017:6570808.
29 Cınar T, Cagdas M, Rencuzogullari I, Karakoyun S, Karabag Y, Yesin M, et al.
Prognostic efficacy of C-reactive protein/albumin ratio in ST elevation
myocardial infarction. Scand Cardiovasc J 2019; 53:83–90.
30 Hammani R, Jdidi J, Mroua F, Kallel R, Hentati M, Abid L, Kammoun S.
Accuracy of the TIMI and GRACE scores in predicting coronary disease in
patients with non-ST-elevation acute coronary syndrome. Rev Port Cardiol
2018; 37:41–49.
31 Bekler A, Altun B, Gazi E, Temiz A, Barutcu A, Güngör Ö, et al. Comparison
of the GRACE risk score and the TIMI risk index in predicting the extent and
severity of coronary artery disease in patients with acute coronary syndrome.
Anatol J Cardiol 2015; 15:801–806.
32 Liu S, Moussa M, Wassef AW, Hiebert BM, Hussain F, Jassal DS. The utility
of systolic and diastolic echocardiographic parameters for predicting
coronary artery disease burden as defined by the SYNTAX score.
Echocardiography 2016; 33:14–22.