Role of Inflammatory Markers in Patients with Coronary Artery Ectasia versus Patients with Obstructive Coronary Artery Disease
Mohamed Abdel-shafy
Tabl1*, Heba Abdel-kader Mansour1, Eman Said El-keshk1,
Hani Asaad Kaddah2
1Department of Cardiology, Benha University, Benha, Egypt
2Department of
Cardiology, Mahalla Cardiology Center, Mahalla, Egypt
Citation: Tabl MAS, Mansour HAK, El-keshk ES, Kaddah HA (2018) Role of
Inflammatory Markers in Patients with Coronary Artery Ectasia versus Patients
with Obstructive Coronary Artery Disease. Cardiolog Res Cardiovasc Med 3: 140. DOI: 10.29011/2575-7083.000040
Abstract
Objective: The
aim of the study is to compare between Eosinophilic Count (EC), Mean Platelet
Volume, (MPV), Neutrophil/Lymphocyte Neutrophil Ratio (NLR) and High Sensitive
CRP (HS-CRP) level in patients with coronary artery ectasia versus patients
with obstructive coronary artery disease.
Methods: 150
patients underwent diagnostic coronary angiography in cardiology departments of
Mahalla cardiology center and Benha University hospitals, divided into three
groups, 50 patients with Coronary Artery Ectasia (CAE), 50 patients with
Obstructive Coronary Artery Disease (O-CAD) and 50 patients as a control group.
Results: All
parameters were found to be significantly increased when comparing patients
have CAE or O-CAD with the controls (P<0.001). Plasma levels of EC and
HS-CRP were significantly higher in CAE patients compared with O-CAD patients
(0.202 ± 0.075, 0.126 ± 0.031/nl, P<0.001),
(2.45 ± 0.5, 2.23 ± 0.42 mg/l, P=0.045) respectively.
Meanwhile levels of MPV and NLR were insignificant in CAE patients compared to
O-CAD patients (7.354 ± 0.623, 7.338 ± 0.486 fL, P=0.642),
(2.857 ± 0.88, 2.667 ± 0.569, P=0.222) respectively.
Conclusion: This
study has revealed a relationship between plasma EC and HS-CRP and Coronary Artery
Ectasia (CAE) in comparison to patients with Obstructive Coronary Artery
Disease (O-CAD). These results confirm that CAE is a more severe inflammatory
process than O-CAD.
Keywords: Angiography;
Coronary Ectasia; Eosinophils; High Sensitive CRP; Inflammatory Markers
Abbreviations: AUROC:
Area Under Receiver Operating Characteristic curve; CAD: Coronary Artery Disease;
CAE: Coronary Artery Ectasia; CI: Confidence Interval; EC: Eosinophilic
Count; HS-CRP: High Sensitive CRP; MPV: Mean Platelet Volume; NLR:
Neutrophil/Lymphocyte Neutrophil Ratio; NPV: Negative Predictive Value; OR: Odds
Ratio; O-CAD: Obstructive Coronary Artery Disease; PPV: Positive
Predictive Value; ROC curve: Receiver Operating Characteristic curve; SN :
Sensitivity; SP: Specificity
1. Introduction
Coronary
Artery Ectasia (CAE) is characterized by an abnormal dilatation of the coronary
arteries, which is a variant of Coronary Artery Disease (CAD) [1]. In general,
CAE is considered to be a different form of vascular remodeling in response to
atherosclerosis; however, the underlying mechanisms responsible for ectasia
formation are clearly unknown [2].
Therefore,
determination of the factors associated with the presence and severity of CAE
may have a salutary influence on the management of these patients. Previous
studies have demonstrated that inflammation, neuro-hormonal process and
cardiovascular risk factors are associated with development of CAE. Although it
has been suggested that CAE is a commonly a variant of O-CAD, a definitive link
between atherosclerosis and ectasia has not been confirmed [3].
Based on the findings obtained from previous studies it was suggested that, a
more severe inflammation could be involved in the pathogenesis of CAE [4]. In
addition, C reactive protein (CRP) is a sensitive marker of systemic
inflammation and the elevation of systemic and local levels of this
inflammatory marker has been associated with an increased risk for
cardiovascular disease [5,6].
This study
will be performed on the hypothesis that a more severe inflammation might be
involved in development of isolated CAE compared to obstructive CAD (O-CAD).
2. Methods
2.1. Study Population
Among patients
with angina pectoris undergoing angiographic procedures, 150 patients were
prospectively selected for this study. On the basis of angiographic findings,
they were divided into three groups; 50 patients with isolated CAE, 50 patients
with obstructive CAD and age-matched, sex-matched, 50 controls with normal
coronary arteries. Medical history, atherosclerotic risk factors, and
medications were interrogated on physical examination. Blood samples were
obtained at least 7 days after coronary angiography to exclude possible effect
of angiography on inflammatory situation. Non-inclusion criteria were as
follows: acute coronary syndromes, known aortic aneurysms, hematological
disorders, acute/chronic infectious diseases, hepatitis or previously known
inflammatory/autoimmune disorders, acute/chronic renal failure, documented
cancer, use of steroids, and renin-angiotensin-aldosterone system blockers. All
patients were provided informed consent for participation in this study.
2.2. Assay of
Inflammatory Markers
Blood samples
were drawn into tubes including EDTA after an 8-h fasting period in the morning
with minimal trauma from antecubital vein. Plasmas were separated by
centrifugation at 3000g for 10 min and then stored at -701ºC.
Absolute cell
counts and mean platelet volume were used in this analysis. C-reactive protein
was estimated. Total lipid profile and fasting glucose were also measured.
2.3. Angiographic
Evaluation
Coronary
angiography was obtained in right and left anterior oblique projection with
caudal and cranial angulations for the left and right coronary system. Images
were recorded in digital format and stored for later analyses. Right anterior
oblique view was considered to evaluate the ectasia for the left coronary
system and left anterior oblique view for the right coronary artery. Evaluations
were visually performed by two experienced angiographers. The vessel diameter
was calculated quantitatively in case of presence of conflict about CAE.
Each major
coronary artery was subdivided into proximal, middle, and distal segments.
Coronary ectasia was defined as a dilation exceeding the 1.5-fold of normal
diameters in major coronary arteries [1,2]. If no adjacent normal segment could
be identified, the mean diameter of the corresponding segment in the control
group was considered as normal value. A luminal narrowing greater than 50% in
the coronary artery was considered as obstructive CAD. Absence of any
atherosclerotic plaques was regarded as normal coronary artery. Patients with
concomitant obstructive and ecstatic lesions were not included in this study.
2.4. Statistical Analysis
Continuous
variables were presented as mean ± SD and categorical variables as number (%).
Comparisons between the groups were performed with Student’s t-test, Mann-
Whitney U test and Fisher’s exact test as appropriate. Kruskal Wallis test was
used for relationship between the severity of CAE and inflammatory markers.
Receiver operating characteristics analysis was used to estimate cut-points for
EC, MPV, NLR and HS-CRP to identify CAE patients in the study population. A P
value of less than 0.05 was considered significant. All analyses were made by
using SPSS 11.0.
3. Results
In the receiver operating
characteristics analysis, EC levels greater than 0.1375/nl identified CAE
patients with 80% sensitivity and 80% specificity (Area Under Curve=0.88,
P<0.001). Similarly, hs-CRP levels greater than 1.925 mg/dl estimated the
patients with 82% sensitivity and 70% specificity (Area Under Curve=0.808,
P<0.001).
A multinomial
logistic regression model was performed for the tested inflammatory markers to
determine the likelihood that participants would have CAE or O-CAD. The result
showed that MPV is an independent predictor for CAE [Odds Ratio (OR) =195.017;
95% Confidence Interval (C.I) = 77.249 – 492.325; p<0.001].
4. Discussion
Coronary Artery Ectasia
(CAE) has been defined as localized or diffuse non-obstructive lesions of the
epicardial coronary arteries, with a luminal dilation ≥ 1.5 times normal of the
adjacent segments or vessel diameter. Isolated CAE has been defined as CAE
without significant coronary artery stenosis. This abnormal dilatation of
coronary arteries can cause angina pectoris and even myocardial infarction due
to vasospasm, dissection or thrombus in patients without coronary artery
disease [1,7].
Therefore,
determination of the factors associated with the presence and severity of CAE
may have a salutary influence on the management of these patients [8].
Previous studies have demonstrated that inflammation, neuro hormonal process
and cardiovascular risk factors are associated with development of CAE.
Although it has been suggested that CAE is a commonly a variant of O-CAD, a
definitive link between atherosclerosis and ectasia has not been confirmed
[3,8].
Plasma
Esinophilic Count (EC) was found to be significantly higher in patients with
isolated CAE compared to both patients with O-CAD or controls (p value <
0.001).
Puri R et al.
and Freeman et al., reported in previous studies that eosinophilic vasculitis
with medial necrosis has been identified at autopsy in otherwise healthy
individuals with spontaneous coronary dissection or rupture [9]. It has
therefore been proposed that cytotoxic substances released from perivascular
eosinophils may result in direct medial destruction, predisposing to aneurysmal
formation or spontaneous intimal dissection and sudden cardiac death [10-19].
Also, Moosbauer et al. and Khoury et al., reported in their studies that
eosinophils are equipped with several granule- associated molecules which play
a role in the occurrence of thrombosis and vascular injury. Also eosinophils
generate an increased tendency to thrombosis through leukocyte, platelet
stimulation and release of tissue factor [20,21].
Neutrophil to
Lymphocyte Ratio (NLR) showed significant increase in CAE and O-CAD groups in
comparison to controls (p value < 0.001). Previously, Işık et al., stated in
their study that NLR is a readily available clinical laboratory value that is
associated with the presence of isolated CAE [3]. Also, Sarli et al., stated
that NLR was significantly higher in patients with CAE than in patients with
normal coronaries [22].
According to
MPV there was significant difference between the CAE and O-CAD in comparison to
controls [p value < 0.001]. The results of Sen et al., confirmed that
patients with CAE have higher MPVs than control subjects with normal coronary
angiograms. The increased MPV values may indicate the altered platelet
reactivity and aggregation in patients with CAE [23,24].
With reference
to HS-CRP, in present study, the mean level of HS-CRP in CAE, O-CAD and control
groups was (2.45 ± 0.5, 2.23 ± 0.42 and 0.68 ± 0.15 respectively) with high
significant increase in patients of CAE and O-CAD compared to controls [p value
< 0.001]. Also there was a significant difference in serum level of HS- CRP
between patients with isolated CAE when compared to patients with O-CAD [p
value = 0.045]. These results were consistent with the results of Wang et al.,
study which reported that HS- CRP levels were significantly higher in patients
with isolated CAE, suggesting that more severe inflammation may be involved in
CAE [25,26].
5. Conclusion
As a result,
current study has revealed a clear relationship between plasma EC and HS-CRP
and Coronary Artery Ectasia (CAE) when compared to patients with obstructive
coronary artery disease or controls. This was in context with the hypothesis of
CAE as a more severe inflammatory process than O-CAD. In spite of insignificant
differences for NLR or MPV in patients with CAE when compared to patients with
O-CAD, MPV was an independent predictor for CAE.
Figure 1: Demographic data of the study groups.
Figure 2: ROC curve analysis regarding CAE.
Variables |
CAE group (n=50) |
O-CAD group (n=50) |
Control group (n=50) |
P values |
||
P1 |
P2 |
P3 |
||||
Mean age Male/Female Risk factors: Hypertension Diabetes Dyslipidemia Smoking Family history of CAD |
57.7 ± 5.9 34/16
30 (60%) 24 (48%) 26 (52%) 26 (52%) 19 (38%) |
58.2 ± 5.9 31/19
21 (42%) 28 (56%) 26 (52%) 27 (54%) 18 (36%) |
58.6 ± 5.2 31/19
25 (50%) 21 (42%) 27 (54%) 23 (46%) 22 (44%) |
0.355 0.529
0.315 0.546 0.841 0.548 0.542 |
0.709 0.529
0.072 0.423 1.00 0.841 0.836 |
0.602 1.00
0.422 0.161 0.841 0.424 0.414 |
P1: CAE versus controls; P2: CAE versus O-CAD; P3: O-CAD versus controls. Variables were presented mean ± SD, and n (%). O-CAD: Obstructive Coronary Artery Disease; CAE: Coronary Artery Ectasia. |
Table 1: Baseline clinical characteristics of the study population.
Variables |
CAE group (n=50) |
O-CAD group (n=50) |
Controls (n=50) |
P values |
||
P1 |
P2 |
P3 |
||||
EC /nl NLR MPV fL Hs-CRP mg/dl
|
0.202 ± 0.075 2.857 ± 0.88 7.354 ± 0.623 2.45 ± 0.5 |
0.126 ± 0.031 2.667 ± 0.569 7.338 ± 0.486 2.23 ± 0.42 |
0.066 ± 0.013 1.117 ± 0.395 5.409 ± 0.499 0.68 ± 0.15 |
<0.001 <0.001 <0.001 <0.001
|
<0.001 0.222 0.642 0.045
|
<0.001 <0.001 <0.001 <0.001
|
P1 = CAE group versus controls; P2 = CAE group versus O-CAD group; P3 = O-CAD group versus controls. O-CAD: Obstructive Coronary Artery Disease; CAE: Coronary Artery Ectasia, HS-CRP: High-Sensitive C-Reactive Protein; EC: Eosinophil Count; NLR: Neutrophil/Lymphocyte Ratio; MPV: Mean Platelet Volume. |
Table 2: Inflammatory markers levels of the study groups.
Cut-off value |
Sensitivity % |
Specifity % |
PPV % |
NPV % |
Accuracy |
AUROC |
p-value |
EC > 0.1375 |
80% |
80% |
66.7% |
88.9% |
80% |
0.888 |
<0.001 (HS) |
NLR > 1.9775 |
88% |
60% |
52.4% |
90.9% |
69.3% |
0.771 |
<0.001 (HS) |
MPV > 7.0115 |
70% |
71% |
54.7% |
82.6% |
70.7% |
0.763 |
<0.001 (HS) |
HS-CRP >1.925 |
82% |
70% |
58.6% |
88.6% |
74% |
0.808 |
<0.001 (HS) |
ROC curve: Receiver Operating Characteristic curve; SN: Sensitivity; SP: Specificity; PPV: Positive Predictive Value; NPV: Negative Predictive Value; AUROC: Area Under Receiver Operating Characteristic curve. |
Table 3: Inflammatory markers as predictors for CAE; ROC curve analysis in reference to controls.
Study groups a |
Inflammatory markers |
Intercept |
Std. Error |
Wald |
Degree of freedom |
Sig. |
Odds ratio |
95% Confidence Interval for Odds ratio |
||
Lower Bound |
Upper Bound |
|||||||||
CAE |
Constant |
-74.516 |
624.132 |
.014 |
1 |
.905 |
|
|
|
|
EC |
25.369 |
4702.258 |
.000 |
1 |
.996 |
104113564502.584 |
.000 |
. b |
||
NLR |
3.052 |
378.475 |
.000 |
1 |
.994 |
21.150 |
.000 |
. b |
||
MPV |
5.273 |
.472 |
124.55 |
1 |
.000 |
195.017 |
77.249 |
492.325 |
||
HS-CRP |
22.184 |
527.589 |
.002 |
1 |
.966 |
4307382465.904 |
.000 |
. b |
||
O-CAD |
Constant |
-63.837 |
624.118 |
.010 |
1 |
.919 |
|
|
|
|
EC |
.958 |
4702.255 |
.000 |
1 |
1.000 |
2.607 |
.000 |
. b |
||
NLR |
2.672 |
378.475 |
.000 |
1 |
.994 |
14.469 |
.000 |
. b |
||
MPV |
4.779 |
.000 |
. |
1 |
. |
118.969 |
118.969 |
118.969 |
||
HS-CRP |
21.252 |
527.588 |
.002 |
1 |
.968 |
1696494334.279 |
.000 |
. b |
||
a. The reference category is: Normal CA group. b. Floating point overflow occurred while computing this statistic. Its value is therefore set to system missing. |
Table 4: Multinomial logistic regression analysis for inflammatory markers for CAE and O-CAD.
- Pahlavan
PS, Niroomand F (2006) Coronary artery aneurysm: a review. Clin Cardiol 29:
439-443.
- Manginas
A, Cokkinos DV (2006) Coronary artery ectasias: imaging, functional assessment
and clinical implications. Eur Heart J 27: 1026-1031.
- Işık
T, Ayhan E, Uyarel H, Tanboğa IH, Kurt M, et al. (2013) Association of
neutrophil to lymphocyte ratio with presence of isolated coronary artery
ectasia. Turk Kardiyol Dern Ars 41: 123-130.
- Hansson
GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J
Med 352: 1685-1695.
- Xu
R, Feng LM, Jun L, Yuan LG, Cheng GZ, et al. (2016) Gender differences in the
association of red cell distribution width and coronary artery disease. Lipid
and Cardiovascular Research 2: 42-47.
- Li
JJ, Nie SP, Qian XW, Zeng HS, Zhang CY (2009) Chronic inflammatory status in
patients with coronary artery ectasia. Cytokine 46: 61-64.
- Eitan
A, Roguin A (2016) Coronary artery ectasia: new insights into pathophysiology,
diagnosis, and treatment. Coron Artery Dis 27: 420-428.
- Ozturk
S, Yetkin S, Waltenberger J (2018) Molecular and cellular insights into the
pathogenesis of coronary artery ectasia. Cardiovas Pathol 35: 37-47.
- Puri
R, Dundon BK, Leong DP, Khurana S, Worthley MI (2009) Hypereosinophilic
Syndrome associated with multiple coronary aneurysms. Int J Cardiol 133: 43-45.
- Fujiwara S, Emoto M, Komatso M, Motoyama K,
Morioka T, et al. (2003) Arterial wall thickness is associated with insulin
resistance in type 2 diabetic patients. Journal of atherosclerosis and
thrombosis 10: 246-252.
- Huang QJ, Zhang Y, Li XL, Li S, Guo YL, et al.
(2014) Clinical features of coronary ectasia in the elderly. J Geriatr Cardiol
11: 185-191.
- Swanton
RH, Thomas ML, Coltart DJ, Jenkins BS, Webb-Peploe MM, et al. (1978) Coronary
artery ectasia--a variant of occlusive coronary arteriosclerosis. Br Heart J
40: 393-400.
- Allen
N, Berry JD, Ning H, Van Horn L, Dyer A, et al. (2011) Impact of blood pressure
and blood pressure change during middle age on the remaining lifetime risk for
cardiovascular disease: the cardiovascular lifetime risk pooling project.
Circulation 125: 37-44.
- Adiloglu
AK, Can R, Nazli C, Ocal A, Ergene O, et al. (2005) Ectasia and severe
atherosclerosis: relationships with Chlamydia pneumoniae, Helicobacter pylori,
and inflammatory markers. Tex Heart Inst J 32: 21-27.
- Gunes YB, Boztosun A, Yildiz A, Metin Esen M,
Saglam M, et al. (2006) Clinical profile and outcome of coronary artery
ectasia. Heart 92: 1159-1160.
- Sudhir
K, Ports TA, Amidon TM, Goldberger JJ, Bhushan V, al. (1995) Increased
prevalence of coronary ectasia in heterozygous familial hypercholesterolemia.
Circulation 91: 1375-1380.
- Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman
MV, et al. (1976) Clinical significance of coronary arterial ectasia. The
American journal of cardiology 37: 217-222.
- Ogbogu PU, Rosing DR, Horne MK (2007)
Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy
Clin North Am 27: 457-475.
- Freeman AF, Avila EM, Shaw PA, Davis
J, Hsu AP, et al. (2011) Coronary artery abnormalities in Hyper-IgE syndrome. J
Clin Immunol 31: 338-345.
- Moosbauer
C, Morgenstern E, Cuvelier SL, Manukyan D, Bidzhekov K, et al. (2007)
Eosinophils are a major intravascular location for tissue factor storage and
exposure. Blood 109: 995-1002.
- Khoury
P, Grayson C, Klion AD (2014) Eosinophils in vasculitis: characteristics and
roles in pathogenesis. Nat Rev Rheumatol 10: 474-483.
- Sarli
B, Diao J, Chunmei Qi, Jingjing Jin, Li Li, et al. (2014)
Neutrophil-to-lymphocyte ratio is associated with severity of coronary artery
ectasia. Angiology 65: 147-151.
- Sansanayudh
N, Anothaisintawee T, Muntham D, McEvoy M, Attia J, et al. (2014) Mean platelet
volume and coronary artery disease: a systematic review and meta-analysis. Int
J Cardiol 175: 433-440.
- Serafettin D, Mustafa Kemal A, Zeynep K, Murat
S, Ayd RT, et al. (2013) Mean platelet volume in patients with coronary artery
ectasia. Postepy Kardiol Interwencyjnej 9: 241-245.
- Yintang
W, Yang W, Shijie Y, Hongjian W, Dong Y, et al. (2016) Independent prognostic
value of high-sensitivity C-reactive protein in patients with coronary artery
ectasia. Chin Med J 129: 2582-2588.
- Tokgozoglu
L, Oktay E, Ozan K, Cem N, Gulsen H, et al. (2004) Interleukin-6 levels are
increased in coronary artery ectasia. Acta Cardiol 59: 515-519.
- Pahlavan PS, Niroomand F (2006) Coronary artery aneurysm: a review. Clin Cardiol 29: 439-443.
- Manginas A, Cokkinos DV (2006) Coronary artery ectasias: imaging, functional assessment and clinical implications. Eur Heart J 27: 1026-1031.
- Işık T, Ayhan E, Uyarel H, Tanboğa IH, Kurt M, et al. (2013) Association of neutrophil to lymphocyte ratio with presence of isolated coronary artery ectasia. Turk Kardiyol Dern Ars 41: 123-130.
- Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352: 1685-1695.
- Xu R, Feng LM, Jun L, Yuan LG, Cheng GZ, et al. (2016) Gender differences in the association of red cell distribution width and coronary artery disease. Lipid and Cardiovascular Research 2: 42-47.
- Li JJ, Nie SP, Qian XW, Zeng HS, Zhang CY (2009) Chronic inflammatory status in patients with coronary artery ectasia. Cytokine 46: 61-64.
- Eitan A, Roguin A (2016) Coronary artery ectasia: new insights into pathophysiology, diagnosis, and treatment. Coron Artery Dis 27: 420-428.
- Ozturk S, Yetkin S, Waltenberger J (2018) Molecular and cellular insights into the pathogenesis of coronary artery ectasia. Cardiovas Pathol 35: 37-47.
- Puri R, Dundon BK, Leong DP, Khurana S, Worthley MI (2009) Hypereosinophilic Syndrome associated with multiple coronary aneurysms. Int J Cardiol 133: 43-45.
- Fujiwara S, Emoto M, Komatso M, Motoyama K, Morioka T, et al. (2003) Arterial wall thickness is associated with insulin resistance in type 2 diabetic patients. Journal of atherosclerosis and thrombosis 10: 246-252.
- Huang QJ, Zhang Y, Li XL, Li S, Guo YL, et al. (2014) Clinical features of coronary ectasia in the elderly. J Geriatr Cardiol 11: 185-191.
- Swanton RH, Thomas ML, Coltart DJ, Jenkins BS, Webb-Peploe MM, et al. (1978) Coronary artery ectasia--a variant of occlusive coronary arteriosclerosis. Br Heart J 40: 393-400.
- Allen N, Berry JD, Ning H, Van Horn L, Dyer A, et al. (2011) Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project. Circulation 125: 37-44.
- Adiloglu AK, Can R, Nazli C, Ocal A, Ergene O, et al. (2005) Ectasia and severe atherosclerosis: relationships with Chlamydia pneumoniae, Helicobacter pylori, and inflammatory markers. Tex Heart Inst J 32: 21-27.
- Gunes YB, Boztosun A, Yildiz A, Metin Esen M, Saglam M, et al. (2006) Clinical profile and outcome of coronary artery ectasia. Heart 92: 1159-1160.
- Sudhir K, Ports TA, Amidon TM, Goldberger JJ, Bhushan V, al. (1995) Increased prevalence of coronary ectasia in heterozygous familial hypercholesterolemia. Circulation 91: 1375-1380.
- Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman MV, et al. (1976) Clinical significance of coronary arterial ectasia. The American journal of cardiology 37: 217-222.
- Ogbogu PU, Rosing DR, Horne MK (2007) Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy Clin North Am 27: 457-475.
- Freeman AF, Avila EM, Shaw PA, Davis J, Hsu AP, et al. (2011) Coronary artery abnormalities in Hyper-IgE syndrome. J Clin Immunol 31: 338-345.
- Moosbauer C, Morgenstern E, Cuvelier SL, Manukyan D, Bidzhekov K, et al. (2007) Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 109: 995-1002.
- Khoury P, Grayson C, Klion AD (2014) Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nat Rev Rheumatol 10: 474-483.
- Sarli B, Diao J, Chunmei Qi, Jingjing Jin, Li Li, et al. (2014) Neutrophil-to-lymphocyte ratio is associated with severity of coronary artery ectasia. Angiology 65: 147-151.
- Sansanayudh N, Anothaisintawee T, Muntham D, McEvoy M, Attia J, et al. (2014) Mean platelet volume and coronary artery disease: a systematic review and meta-analysis. Int J Cardiol 175: 433-440.
- Serafettin D, Mustafa Kemal A, Zeynep K, Murat S, Ayd RT, et al. (2013) Mean platelet volume in patients with coronary artery ectasia. Postepy Kardiol Interwencyjnej 9: 241-245.
- Yintang W, Yang W, Shijie Y, Hongjian W, Dong Y, et al. (2016) Independent prognostic value of high-sensitivity C-reactive protein in patients with coronary artery ectasia. Chin Med J 129: 2582-2588.
- Tokgozoglu L, Oktay E, Ozan K, Cem N, Gulsen H, et al. (2004) Interleukin-6 levels are increased in coronary artery ectasia. Acta Cardiol 59: 515-519.