Coronary Heart Disease

Angiology
2014, Vol 65(1) 60-64
A New Parameter Predicting Chronic The Author(s) 2013
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Total Occlusion of Coronary Arteries: DOI: 10.1177/0003319713486339
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Platelet Distribution Width

Mehmet Akif Vatankulu, MD1, Osman Sonmez, MD1,

Gokhan Ertas, MD2, Ahmet Bacaksiz, MD1, Murat Turfan, MD1,
Ercan Erdogan, MD1, Abdurrahman Tasal, MD1, Seref Kul, MD1,
Huseyin Uyarel, MD1, and Omer Goktekin, MD1

Abstract
Platelet distribution width (PDW) measures the variability in platelet size and is a marker of platelet activation. We investigated
whether PDW is associated with the extent of coronary artery disease (CAD) and coronary total occlusions (CTOs). We studied
162 patients: 108 had a coronary lesion with a diameter stenosis of 50%, the CAD() group, and 54 patients had normal
coronary anatomy, the CAD() group. The CAD() group was subdivided into CAD() CTO() and CAD() CTO() groups.
Among patients with CAD, the CTO() group had a significantly greater PDW (%) than the CTO() group (16.9 + 2.8, 15.4 +
3.0, and 15.4 + 1.9, respectively; P .008). In a receiveroperating characteristic analysis, a PDW cut point of 15.7% was
identified in patients with CTO() (area under curve 0.64, 95% confidence interval 0.54-0.75). A PDW value of more than
15.7% demonstrated a sensitivity of 64% and a specificity of 66%. The PDW is a simple platelet index that may predict the presence
of CTO.

Keywords
platelet distribution width, coronary artery disease, total occlusion

Introduction Patients and Methods

Atherosclerosis is a chronic inflammatory disease that may
progress to thrombotic complications.1,2 Chronic coronary total
occlusions (CTOs) are generally considered to be lesions with
duration of >3 months in which the vessel shows either com-
plete interruption of antegrade blood flow on angiography or
only minimal contrast penetration through the lesion without
distal vessel opacification.3 The CTO most often arise from
thrombotic occlusion, followed by thrombus organization.4
The lesions are typically characterized by heavy plaque burden
within the artery. Mean platelet volume (MPV) and platelet dis-
tribution width (PDW) are simple platelet indices that increase
during platelet activation.5-10 The PDW directly measures
the variability in platelet size and is a marker of platelet
activation.11 However, only few studies have investigated the
relationship between this index and coronary artery disease
(CAD),5,12-14 and none have addressed the association between
PDW and CTO. Thus, the aim of the current study was to inves-
tigate whether PDW is associated with the extent of CAD and
CTO. We hypothesized that PDW would be associated with a
greater complexity of CAD as assessed using the SYNTAX
score (SS) and would be associated with CTO. The SS is an
angiographic tool used to grade the complexity of CAD.
Patient Selection
The study population included 162 patients who were referred
for elective coronary angiography for stable angina pectoris
between March 2011 and August 2012. All patients recruited
into the study had objective signs of ischemia. Patients present-
ing with acute myocardial infarction (AMI), coronary artery
bypass grafting, end-stage renal disease, malignancy, prior blood
transfusion or hematological disorder such as idiopathic throm-
bocytopenic purpura, aplastic anemia, or other diseases that have
direct impact on platelet size and volume were excluded from
the study. Patients (n 108) who had coronary lesion with a dia-
meter stenosis of 50% were included in the CAD() group; 54
1
Department of Cardiology, Faculty of Medicine, BezmiAlem Vakif University,
Istanbul, Turkey
2
Deparment of Cardiology, Dr. Siyami Ersek Thoracic and Cardiovascular
Surgery Training and Research Hospital, Istanbul, Turkey
Corresponding Author:
Osman Sonmez, Department of Cardiology, Faculty of Medicine, BezmiAlem
Vakif University, Istanbul, Turkey.
Email: osmansonmez2000@gmail.com
Vatankulu et al 61

Table 1. Baseline Characteristics of Groups.a

CAD(), n 54 CAD() CTO(), n 54 CAD() CTO(), n 54 P

Age, years 57 + 10 62 + 9 59 + 12 .08

Female/male 34/12 16/32 11/38 .0001
Diabetes, % 26 37 43 .11
Hypertension, % 43 50 50 .78
Hyperlipidemia, % 30 37 54 .02
BMI, kg/m2 28.9 + 2.5 29.9 + 2.9 31.5 + 2.7 .12
WBC count, 103 7.1 + 1.9 7.5 + 2.2 7.7 + 2.0 .40
Neutrophil count, 103 4.0 + 1.6 4.6 + 1.6 4.6 + 1.7 .07
Lymphocyte count, 103 2.2 + 0.8 2.1 + 0.8 2.0 + 0.7 .58
Platelet count, 103 268 + 67 246 + 66 230 + 56 .015 .012b
MPV, fL 9.2 + 0.9 9.3 + 1.1 9.6 + 0.9 .16
PDW, % 15.4 + 1.9 15.4 + 3.0 16.9 + 2.8 .008 .02-.02c
Hemoglobin, g/dL 12.3 + 1.7 12.4 + 1.5 13.0 + 1.9 .12
Creatinine, mg/dL 0.9 + 0.7 0.9 + 0.4 0.9 + 0.3 .99
LDL, mg/dL 121 31 146 + 39 113 + 32 .008
SYNTAX score 14.9 + 10.1 21.4 + 10.5 .008d
Aspirin, % 12 16 18 S
b-Blocker, % 5 9 13 NS
ACE inhibitor, % 20 26 29 NS
Statin, % 14 18 27 .008
Abbreviations: BMI, body mass index; WBC, white blood cell; NLR, neutrophil-to-lymphocyte ratio; MPV, mean platelet volume; PDW, platelet distribution width;
ACE, angiotensin converting enzyme; CAD, coronary artery disease; CTO, coronary total occlusion; LDL, low-density lipoprotein.
a
Results are expressed as mean + standard deviation or frequency (within group percentage). Analysis of variance and chi-square test are used.
b
Bonferroni post hoc test CAD() group and CAD() CTO() group.
c
Bonferroni post hoc test CAD(), CAD() CTO(), CAD() CTO(), and CAD() CTO() groups.
d
Student t test.

patients who had normal coronary anatomy were included in the
CAD() group. The CAD() group was subdivided into the
CAD() CTO() group and CAD() CTO() group. The CTO
was considered to be lesions with a duration of >3 months, in
which the vessel shows no antegrade blood flow on angiography
or only minimal contrast penetration through the lesion without
distal vessel opacification.3 A clinical history of risk factors such
as age, sex, diabetes mellitus (DM), hypertension (HT), hyperch-
olesterolemia (HL), and family history of cardiovascular disease
was recorded. For each patient, height, weight, and body mass
index were calculated. Hemoglobin, white blood cell (WBC),
platelet (Plt) count, MPV, and PDW were measured as part of
the automated complete blood count using a Sysmex XT-
1800i (Sysmex Corporation, Kobe, Japan) hematology analyzer.
Baseline neutrophil-to-lymphocyte ratio was measured by divid-
ing the neutrophil count by the lymphocyte count. Patients with
WBC count >12 000 cells/mL or <4000 cells/mL and high body
temperature >38 C were excluded from the study.
SYNTAX Score
The SS is an angiographic index used to grade the complexity
of CAD. Each coronary lesion with a diameter stenosis of
50%, in vessels 1.5 mm, should be scored. The online latest
updated version (2.1) was used for the calculation of the SS
(www.syntaxscore.com).15
Statistical Analyses
The statistical analyses were performed using software (SPSS
15.0; SPSS Inc, Chicago, Illinois). Continuous variables are
expressed as mean + standard deviation or median (interquar-
tile range) when appropriate. Categorical variables are
expressed as percentages. To compare parametric continuous
variables, Student t test or analysis of variance was used; to com-
pare nonparametric continuous variables, the Mann-Whitney
U test or the Kruskall-Wallis test was used. To compare cate-
gorical variables, the chi-square test was used. The Pearson
correlation analysis was used to correlate MPV and SS and also
PDW and SS. Multivariate logistic regression analysis was
used to identify the independent predictors of CTO. All vari-
ables showing significance values of less than 0.1 on univariate
analysis (age, sex, DM, HT, HL, platelet count, MPV, and
PDW) were included in the model. A 2-tailed P < .05 was
considered significant.
Results
The baseline characteristics of the groups are presented in
Table 1. In 162 patients (mean age 59.6 + 11.9, 58% male),
PDW ranged from 10.7% to 48.7% (median 15.8%, mean
16.04 + 3.73%). Among patients with CAD, the CTO()
group had a significantly greater PDW (%) value than CTO()
group (16.9 + 2.8, 15.4 + 3.0, and 15.4 + 1.9, respectively;
P .008). Patients in the group without CAD were signifi-
cantly younger female individuals, and the CAD() CTO()
group had significantly more hyperlipidemia history. In con-
trast to the PDW (%), the CAD() group had a significantly
higher platelet count (103 cells/mL; 268 + 67, 246 + 66 and
230 + 56, respectively; P .015). There was no significant
difference in MPV. The CAD() CTO() group had higher
62 Angiology 65(1)

Table 2. Predictors of CTO in Multivariate Logistic Regression

Analysis.

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

Age, years .26

Male, % (0.23-1.4) .23
Diabetes mellitus, % (0.34-1.7) .53
Hyperlipidemia, % (0.2-1.0) .06 2.0 (0.8-4.2) .09
Platelet count, 103 .21
MPV, fL .21
PDW, % .02 1.2 (1.0-1.4) .01
Abbreviations: MPV, mean platelet volume; PDW, platelet distribution width;
OR, odds ratio; CI, confidence interval; CTO, coronary total occlusion.

Figure 1. Correlation between mean platelet volume (MPV) and

SYNTAX score; Pearson test was used.

Figure 2. Correlation between platelet distribution width (PDW)

and SYNTAX score; Pearson test was used.

coronary complexity as assessed by SS than the CAD()

CTO() group (21.4 + 10.5 and 14.9 + 10.1; P .008).
In the correlation analyses, there were no correlation
between PDW and SS and also MPV and SS (Figures 1 and
2). The CAD() CTO()and CAD() CTO() groups were
compared in the univariate analysis. Variables found to be sig-
nificant in univariate analyses were entered into multivariate
logistic regression analysis.
In univariate analysis, age, male sex, HL, platelet, MPV,
high SS, and PDW were predictors of CTO. In the multiple
logistic regression analysis, PDW (odds ratio 1.2, 95% con-
fidence interval [CI] 1.0-1.4; P .01) and HL were identified
as independent predictors of CTO in our model (Table 2).
In a receiveroperating characteristic analysis, a cut point of
15.7% for PDW was identified in patients with CTO() (area
Figure 3. Receiveroperating characteristic analysis and curve for
predicting coronary total occlusions (CTO).
under curve 0.64, 95% CI 0.54-0.75). A PDW value more
than 15.7% demonstrated a sensitivity of 64% and a specificity
of 66% (Figure 3).
Discussion
We found a relation between PDW and CTO of coronary
arteries in stable CAD. Our findings suggest that high levels
of PDW can predict CTO in CAD.
Platelets play a role in every spectrum of CAD.7 The MPV
and PDW are simple platelet indices that increase during
Vatankulu et al
platelet activation. The MPV is an extensively studied platelet
activation marker in coronary atherosclerosis.5-10 The PDW
directly measures the variability in platelet size. According to
the recent studies, PDW is a more specific marker of platelet
activation11 and may provide more information than MPV.14
Coronary artery CTO most often arises from thrombotic occlu-
sion, followed by thrombus organization and tissue aging.4 The
histopathological progress of CTO is not clearly defined. A
thrombus develops after coronary artery occlusion, and then
they progress to an organized thrombus that is more solid than
fresh thrombus formation, with dense collagen-rich fibrous
tissue.16-18 To the best of our knowledge, we have not identi-
fied any literature reporting that PDW values predict CTO. In
their study, De Luca et al did not describe a separate CTO
group, but the high PDW group had a high, but not significant,
CTO percentage. However, their study group had approxi-
mately 30% normal coronary artery, and CAD() group
was not compared with CAD() group. Ege et al showed that
PDW levels were higher in patients with an occluded saphe-
nous vein graft.13
In the present study, there were no relationship between
CAD() and CAD() groups for MPV values as in studies
conducted by others.19,20
Supporting our data, De Luca et al showed that PDW was
inversely correlated with the total platelet count.14 There are
few data describing the relationship between PDW and the
extent of CAD.5,14 However, the issue is confusing because
there are conflicting results about the relationship between
PDW and CAD. De Luca et al showed that PDW is not related
to the extent of CAD and carotid atherosclerosis. Khandekar
et al reported that MPV, PDW, and platelet large cell ratio were
significantly higher in patients with unstable angina or AMI.21
Ihara et al reported that MPV, platelet large cell ratio, and PDW
were significantly higher in angiographically negative group
than in angiographically positive group. They concluded that
lower platelet large cell ratio seems to identify patients with
positive coronary angiography.22 Finally, CTO group had sig-
nificantly more hyperlipidemia history and had significantly
more statin therapy. According to recently published data, Akin
et al showed that atorvastatin therapy has positive effect on
hematologic parameter in patients with hyperlipidemia.23
These findings can explain our low sensitivity and specificity
values for predicting CTO.
Major limitations of our study include the small population
and lack of measured inflammatory markers. Second, we did
not measure and correlate other inflammatory markers or plate-
let function tests.
The PDW is a simple platelet index that may predict the
presence of CTO. However, prospective studies with more
patients are needed to support this finding.
Authors Note
The preliminary results of this study have been accepted as
abstract in 28th National Cardiology Congress, November 14,
2012, Istanbul.
63
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
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