Journal of Cardiology 63 (2014) 358–364

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Journal of Cardiology
journal homepage: www.elsevier.com/locate/jjcc

Original article

Current cigarette smoking is an independent risk factor for subacute

stent thrombosis in acute myocardial infarction patients
Tsuyoshi Honda (MD) ∗ , Kazuteru Fujimoto (MD), Yuji Miyao (MD),
Hidenobu Koga (MD), Masanobu Ishii (MD)
Department of Cardiology, Cardiovascular Center, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Background: Acute myocardial infarction (AMI) is prevalent and has serious consequences including re-
Received 16 May 2013 infarction and death. Cigarette smoking is a coronary risk factor for AMI, although a “smoker’s paradox”
Received in revised form for AMI has been reported in Western countries. On the other hand, some researchers have reported that
16 September 2013
smoking is associated with subacute stent thrombosis (SAST) after AMI. However, the occurrence of this
Accepted 6 October 2013
condition is not well documented in Japan. The aim of this study was to clarify how prior smoking status
Available online 14 November 2013
may affect prognosis, including SAST, in Japanese patients with AMI.
Methods: A total of 266 consecutive patients with AMI were enrolled retrospectively in the study if they
Keywords:
Acute myocardial infarction
had undergone emergency coronary intervention (bare metal stent) within 24 h of symptom onset, and
Current smoker had a 5–10 month follow-up examination. The patients were divided into three groups based on their
Subacute stent thrombosis cigarette smoking status (non-smokers, past smokers, and current smokers).
Results: Current smokers were significantly younger than the other two groups, although their levels of
low density lipoprotein-cholesterol and triglyceride were significantly higher. White blood cell count
and hemoglobin level on admission were also significantly higher in current smokers compared with the
other two groups. The incidence of SAST was significantly higher in current smokers than in the other
groups, although the occurrence of heart failure after AMI was similar in the three groups. On the other
hand, improvement in left ventricular ejection fraction was observed in non-smokers and past smokers,
but not in current smokers. Multiple logistic analysis revealed that current smoking was an independent
risk factor for SAST (odds ratio 5.4; p < 0.05). Current smokers were about five times more likely to have
a SAST compared with non-smokers.
Conclusions: These findings indicate that current cigarette smoking predicts SAST after primary percuta-
neous coronary intervention for AMI in Japanese patients.
© 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Introduction that female smokers are more likely to experience cardiovascular

Cigarette smoking is one of the major classical risk factors for
atherosclerosis and cardiovascular disease [1,2] including acute
myocardial infarction (AMI) [3–5]. AMI is a leading cause of death in
adults and it is therefore important to evaluate patient risk includ-
ing future adverse events in the early stages after an AMI.
Smokers who have had an AMI have lower mortality rates
than non-smokers despite having an increased risk for coronary
artery disease. Several studies have reported this “smoker’s para-
dox” [6–8]. In contrast, other studies have shown that patients
who continue to smoke after an AMI have increased mortality, and
complications 6 months after an AMI than male smokers [9,10].
Although the “smoker’s paradox” associated with an AMI has been
studied in Western countries, the condition is less well documented
in Japan.
On the other hand, it has been reported that current cigarette
smoking is a risk factor for subacute stent thrombosis (SAST) after
an AMI in Western countries [11–13]. However this association has
also not been investigated extensively in Japan.
This study therefore examined the association between prior
smoking status and prognosis including SAST in Japanese patients
with an AMI.

Methods
∗ Corresponding author at: Department of Cardiology, Cardiovascular Center,
National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-ku,
Study population
Kumamoto 860-0008, Japan. Tel.: +81 96 353 6501; fax: +81 96 325 2519.
E-mail addresses: tsuyohonda-circ@umin.ac.jp, thonda@kumamoto2.hosp.go.jp The study involved a retrospective analysis of 296 consecutive
(T. Honda). patients who underwent percutaneous coronary intervention (PCI)

0914-5087/$ – see front matter © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jjcc.2013.10.007
 T. Honda et al. / Journal of Cardiology 63 (2014) 358–364
at Kumamoto Medical Center within 24 h after the onset of AMI
and had a follow-up examination 5–10 months later. The diagno-
sis of AMI was made using the Universal Definition of Myocardial
Infarction [14]. As it is possible that differences in PCI [thrombolysis,
POBA (plain old balloon angioplasty], BMS (bare metal stent), and
DES (drug-eluting stent)] may influence the prognosis of patients
with AMI, the study population only included 266 patients treated
with a BMS. The main exclusion criteria were the presence of malig-
nant disease, severe renal failure, known hepatic disease, and the
lack of a follow-up examination. The primary endpoint was stent
thrombosis in patients treated with a BMS.
The patients were divided into three groups according to their
prior smoking status (current smokers, past smokers, and non-
smokers). We defined current smokers as individuals who had
smoked any tobacco products in the previous 12 months, including
those who had quit within the past year. Past smokers were defined
as those who had quit more than one year earlier.
Blood pressure, heart rate (HR), plasma glucose (PG), white
blood cell (WBC) count, glomerular filtration rate (GFR), and
hemoglobin (Hb) were measured on admission to the emergency
unit of Kumamoto Medical Center. GFR was calculated using the
abbreviated Modification of Diet in Renal Disease Study formula
[15]. Creatine phosphokinase (CK) was measured every 4–6 h after
admission in all patients. Blood samples for measures of PG and
WBC count were obtained at the time of hospital admission. Total
cholesterol (T-Cho), high-density lipoprotein cholesterol (HDL-C),
low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and
hemoglobin A1c (HbA1c) levels were measured in the fasting state
the day after admission.
Analysis of coronary risk factors for coronary artery disease
The traditional risk factors for coronary artery disease used in
the statistical analyses were hypertension (HT), lipid profiles (T-
Cho, HDL-C, LDL-C, and TG), current cigarette smoking habit, body
mass index (BMI), and diabetes mellitus (DM).
HT was defined as a blood pressure ≥140/90 mmHg and/or
the use of antihypertensive medication, dyslipidemia as a HDL-
C < 40 mg/dl, and/or LDL-C > 140 mg/dl, and/or TG > 150 mg/dl,
and/or the use of antidyslipidemic medication, and DM as a fas-
ting blood glucose ≥ 126 mg/dl, and/or HbA1c ≥6.5%, or the use of
antidiabetic medication [16].
Coronary angiography and coronary intervention
Emergency coronary intervention using BMSs was performed
in all patients. The AMI sites were divided into two groups (ante-
rior AMI and non-anterior AMI). A diseased coronary artery was
defined as stenosis ≥75%, with the patients being divided into
two groups (single-vessel disease and multivessel disease). Reper-
fusion therapy was used at the discretion of the attending physician
and the type of BMS was selected by the physician (DRIVERTM ,
Medtronic, Minneapolis, MN, USA; VISIONTM , Abbott, Abbott
Park, IL, USA; S-STENTTM , Biosensors International, Singapore;
IntegrityTM , Medtronic, USA; TSUNAMITM , Terumo, Tokyo, Japan;
LibertéTM , Boston Scientific, Natick, MA, USA).
Dual anti-platelet therapy
All patients received aspirin (200 mg) and were given a 300 mg
loading dose of clopidogrel before the angioplasty. Aspirin was con-
tinued indefinitely, with a dose of 100 mg daily, and clopidogrel was
continued for at least 1 month with a daily dose of 75 mg.
359
Evaluation of left ventricular end-diastolic volume index and left
ventricular ejection fraction by echocardiography
All patients underwent echocardiography performed by labora-
tory technicians after admission and at follow-up. The values for
left ventricular (LV) end-diastolic volume were corrected for body
surface area and expressed as the LV end-diastolic volume index
(LVEDVI).
Subacute stent thrombosis
SAST was defined according to the Academic Research Consor-
tium definition and was categorized according to the time of the
event as subacute (from 24 h to 30 days) [17].
Heart failure and major cardiovascular events
Heart failure was defined as dyspnea and/or edema that
required hospitalization, accompanied by pulmonary congestion
on a chest roentgenogram, and LV dysfunction on an echocardio-
gram.
Major cardiovascular events were defined as death, myocardial
infarction, or cerebrovascular events after discharge.
Target lesion revascularization
A clinically driven target lesion revascularization (TLR) proce-
dure was defined as one performed because of recurrent angina
and/or documented ischemia on noninvasive tests, with >70%
diameter stenosis by quantitative coronary angiography (QCA) in
the absence of symptoms [17].
Statistical analysis
The subjects were divided into three groups according to their
prior smoking status. Differences in frequencies were analyzed
using the chi-square method. A comparison of continuous vari-
ables in the three groups was performed using a one-way analysis
of variance (ANOVA), followed by Scheffé’s procedure to compare
individual groups. Continuous variables were compared in the two
groups using a two-tailed paired t-test. Odds ratios (OR) and 95%
confidence intervals (CI) for SAST were calculated using logistic
regression analysis. Differences with p < 0.05 were considered sta-
tistically significant in all the analyses. Data were expressed as the
mean ± SD.
Results
Clinical characteristics at baseline
Current smokers were significantly younger than non-smokers.
The percentage of males in the non-smokers group was signifi-
cantly lower than in the current and past smokers groups. The
percentage of HT was lower in the current smokers group com-
pared with the other two groups. Although LDL-C and TG levels
were increased significantly in current smokers compared with the
other two groups, the percentage of patients treated with statins
was lowest in the current smokers group (Table 1).
Clinical and angiographic characteristics of acute myocardial
infarction
There were no differences in blood pressure or HR on admis-
sion between the three groups. Anterior AMI was more frequent
in current smokers compared with the other groups. However, ST-
elevation myocardial infarction (STEMI), previous MI, preinfarction
360 T. Honda et al. / Journal of Cardiology 63 (2014) 358–364

Table 1
Clinical characteristics of the patients at baseline.

Non-smokers Past smokers Current smokers p-Value

n = 84 n = 79 n = 103

Age (yrs) 75 ± 8 71 ± 11 59 ± 11*,†

Male (%) 25 (29.8) 72 (91.1) 92 (89.3) <0.0001
BMI (kg/m2 ) 22.8 ± 3.0 23.3 ± 3.0 24.1 ± 3.1*
Hypertension (%) 59 (70.2) 49 (62.0) 54 (52.4) 0.0445
Dyslipidemia (%) 38 (45.2) 38 (48.1) 49 (47.6) 0.925
Diabetes mellitus (%) 23 (27.4) 24 (30.4) 29 (28.2) 0.908
T-Cho (mg/dl) 191 ± 40 184 ± 39 201 ± 39†
HDL-C (mg/dl) 47 ± 13 45 ± 10 42 ± 11*
LDL-C (mg/dl) 120 ± 32 117 ± 31 133 ± 35*,†
TG (mg/dl) 107 ± 59 108 ± 51 152 ± 110*,†
Hemoglobin A1c (%) 5.9 ± 1.3 6.0 ± 1.2 6.3 ± 1.8

Previous medical treatment

ACE-I (%) 4 (4.8) 2 (2.5) 2 (1.9) 0.491
ARB (%) 22 (26.2) 13 (16.5) 17 (16.5) 0.153
Beta-blocker (%) 1 (1.2) 5 (6.3) 3 (2.9) 0.173
Statin (%) 20 (23.8) 13 (16.5) 9 (8.7) 0.0189

BMI, body mass index; T-Cho, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; ACE-I, angiotensin-
converting enzyme inhibitor; ARB, angiotensin receptor blocker.
*
p < 0.05 vs non-smokers.
†
p < 0.05 vs past smokers.

angina, and coronary multi-vessel involvement were not signifi-
cantly different in the three groups. WBC count and hemoglobin
level were increased significantly in current smokers compared
with the other groups. There was no difference in LVEDVI and LV
ejection fraction (LVEF) at baseline in the three groups. The diam-
eter of the stents implanted in the culprit lesion was significantly
greater in current smokers than in non-smokers (Table 2).
Clinical characteristics of patients at follow-up
The incidence of SAST was increased significantly in current
smokers compared with the other two groups. The follow-up period
of this study was 197 ± 65 days. Time to SAST was 6 ± 4 days after
primary PCI. All SASTs observed in this study were definite (stent
thrombosis category of Academic Research Consortium), and each
outcome was non-fatal AMI [17].
In this study, the incidence of SAST were 4 (3.2%) of 124
DRIVERTM stents, 3 (6.7%) of 45 VISIONTM stents, 2 (3.4%) of 58
S-STENTTM stents, 1 (6.3%) of 16 IntegrityTM stents, 0 (0%) of 17
TSUNAMITM stents, and 0 (0%) of 6 LibertéTM stents, respectively.
There was no significant difference for the incidence of SAST among
these stents.
There were no significant differences in the occurrence of
heart failure. In this study, 6 major cardiovascular events (4
death, 2 myocardial infarction, and 0 cerebrovascular events) were
observed during the follow-up period. Incidence of major cardio-
vascular events in each group was 3 (3.6%) of 84 non-smokers, 1
(1.3%) of 79 past-smokers, 2 (1.9%) of 103 smokers, respectively.
There was no significant difference with regard to major cardio-
vascular events (Table 3).
Improvement in LVEF was observed in non-smokers and past
smokers, but not in current smokers (Fig. 1).

Table 2
Clinical and angiographic characteristics of acute myocardial infarction.

Non-smokers Past smokers Current smokers p-Value

n = 84 n = 79 n = 103

Time from chest pain to PCI (h) 8.1 ± 7.1 7.5 ± 6.9 6.4 ± 5.9
SBP on admission (mmHg) 129 ± 31 136 ± 32 136 ± 33
HR on admission (bpm) 75 ± 22 76 ± 26 77 ± 20
Previous MI (%) 5 (6.0) 7 (8.9) 8 (7.8) 0.775
Preinfarction angina (%) 32 (38.1) 24 (30.4) 37 (35.9) 0.567
STEMI (%) 60 (71.4) 56 (70.9) 80 (77.7) 0.501
Anterior MI (%) 41 (48.8) 31 (39.2) 59 (57.3) 0.0542
Killip > I (%) 22 (26.2) 15 (19.0) 19 (18.4) 0.376
Coronary multi-vessel involvement (%) 35 (41.7) 33 (41.8) 32 (31.1) 0.218
PG on admission (mg/dl) 185 ± 82 172 ± 63 196 ± 114
WBC count on admission (/mm3 ) 9426 ± 3327 9305 ± 2854 10,953 ± 3468*,†
GFR on admission (ml/min/1.73 m2 ) 72.1 ± 28.0 70.5 ± 25.9 79.0 ± 29.1
Hemoglobin on admission (g/dl) 12.6 ± 1.9 13.7 ± 1.8* 14.8 ± 1.5*,†
Peak CK (IU/l) 2457 ± 2509 2438 ± 2580 3112 ± 2924
LVEDVI at baseline (ml/m2 ) 59.3 ± 14.5 57.8 ± 15.2 56.8 ± 14.7
LVEF at baseline (%) 58.9 ± 11.7 58.6 ± 11.2 59.9 ± 10.4
TIMI grade 3 after PCI (%) 66 (78.6) 60 (75.9) 83 (80.6) 0.786
Stent diameter at culprit lesion (mm) 2.94 ± 0.45 3.01 ± 0.42 3.10 ± 0.44*
Stent length implanted at culprit lesion (mm) 22 ± 9 27 ± 17* 22 ± 8†

PCI, percutaneous coronary intervention; SBP, systolic blood pressure; HR, heart rate; MI, myocardial infarction; STEMI, ST-elevation myocardial infarction; PG, plasma
glucose; WBC, white blood cell; GFR, glomerular filtration rate; CK, creatine phosphokinase; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular
ejection fraction; TIMI, thrombolysis in myocardial infarction.
*
p < 0.05 vs non-smokers.
†
p < 0.05 vs past smokers.
 T. Honda et al. / Journal of Cardiology 63 (2014) 358–364 361

Table 3
Clinical characteristics of patients at follow-up.

Non-smokers Past smokers Current smokers p-Value

n = 84 n = 79 n = 103

Subacute stent thrombosis (%) 1 (1.2) 1 (1.3) 8 (7.8) 0.0240

Time from PCI to follow-up (day) 194 ± 77 197 ± 62 199 ± 59
CHF during follow-up (%) 7 (8.3) 2 (2.5) 5 (4.9) 0.246
Major cardiovascular events (%) 3 (3.6) 1 (1.3) 2 (1.9) 0.589
LVEDVI at follow-up (ml/m2 ) 65.0 ± 17.1 62.5 ± 14.7 62.1 ± 18.8
LVEF at follow-up (%) 63.0 ± 11.4 62.5 ± 10.3 61.4 ± 11.5
Target lesion revascularization (%) 14 (16.7) 22 (27.8) 25 (24.3) 0.218
Active medical treatment
Aspirin (%) 84 (100) 78 (98.7) 103 (100) 0.305
ACE-I (%) 51 (60.7) 47 (59.5) 63 (61.2) 0.973
ARB (%) 24 (28.6) 16 (20.3) 24 (23.3) 0.451
Beta-blocker (%) 27 (32.1) 29 (36.7) 31 (30.1) 0.636
CaCB (%) 24 (28.6) 26 (32.9) 31 (30.1) 0.830
Nitrate (%) 15 (17.9) 18 (22.8) 17 (16.5) 0.542
Diuretics (%) 19 (22.6) 11 (13.9) 14 (13.6) 0.193
Statin (%) 65 (77.4) 47 (59.5) 80 (77.7) 0.0111
EPA (%) 4 (4.8) 4 (5.1) 9 (8.7) 0.460
Thiazolidindione (%) 0 (0.0) 2 (2.5) 2 (1.9) 0.372
DPP4-I (%) 4 (4.8) 3 (3.8) 8 (7.8) 0.472
Insulin therapy (%) 11 (13.1) 4 (5.1) 6 (5.8) 0.100

PCI, percutaneous coronary intervention; CHF, congestive heart failure; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; ACE-I,
angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CaCB, calcium channel blocker; EPA, eicosapentaenoic acid; DPP4-I, dipeptidyl peptidase-4
inhibitor.

Logistic analysis for the risk of SAST
Multiple logistic analysis incorporating all the clinical vari-
ables in Tables 1 and 2 showed that current smoking [odds ratio
(OR) 5.35; 95% confidence interval (CI) 1.00–28.5; p < 0.05] was an
independent risk factor for stent thrombosis with the strongest
predictive potential for the condition (Table 4).
In 20 of 266 patients, clopidogrel was changed to cilostazol with
a daily dose 200 mg due to side effects. However, this variance was
Fig. 1. Comparisons of LVEDVI and LVEF at baseline and follow-up. LVEDVI, left ven-
tricular end-diastolic volume index; LVEF, left ventricular ejection fraction. White
box: baseline, black box: follow-up.
not significantly associated with incidence of SAST (OR 1.39; 95%
CI 0.17–11.5; p = 0.76).
Discussion
We report for the first time that current cigarette smoking
increases the risk for SAST in Japanese patients with AMI treated
with BMSs. In addition, improvement in LVEF was not observed
in current smokers, although it was observed in past smokers and
non-smokers. However, current cigarette smoking did not exacer-
bate the occurrence of congestive heart failure during follow-up.
The incidence of SAST in this study (3.8%) was somewhat higher
in comparison with previous reports (0.71–4.5%) [11–13,18]. First,
the regimen of dual antiplatelet therapy (aspirin plus clopidogrel)
in this study was different from that of Ishikawa’s study (aspirin
plus ticlopidine) [18]. The difference in dual anti-platelet therapy
might be associated with the incidence of SAST, because a recent
study reported that three quarters of Japanese patients with acute
coronary syndrome (ACS) carried CYP2C19 variant alleles and the
majority had increased platelet reactivity during the early phase of
ACS after standard maintenance dose of clopidogrel [19]. Second,
the prevalence of CYP2C19 polymorphism is high in Asians com-
pared to Westerners and Caucasians [19]. The association between
the occurrence of SAST and CYP2C19 polymorphism is interest-
ing, but it might be beyond the scope of the present study. Future
research is needed for further investigation [20]. Finally, this study
excluded AMI patients who did not undergo the follow-up exami-
nation. This might be associated with the somewhat high incidence
of SAST.
The current smokers in the study were significantly younger
than non- and past smokers, and were more likely to be male.
In addition, the prevalence of hypertension was lower in current
smokers, although there was no significant difference in the preva-
lence of dyslipidemia and diabetes in the three groups. Previous
researchers have reported that the prevalence of smoking in males
increased over time, and that smokers were younger at presen-
tation with fewer co-morbidities than non-smokers [10]. These
findings indicate that smokers experience ACS events earlier than
non-smokers, and that smoking is an important risk factor for ACS.
The levels of HDL-C were significantly lower, but LDL-C and TG
were significantly higher in current smokers than non-smokers as
362 T. Honda et al. / Journal of Cardiology 63 (2014) 358–364

Table 4
Logistic analysis for the risk of subacute stent thrombosis.

Univariate model Multivariate model

OR (95% CI) p-Value OR (95% CI) p-Value

Age 0.967 (0.921–1.02) 0.175 – –

Male 3.80 (0.473–30.5) 0.209 – –
BMI 1.09 (0.886–1.33) 0.429 – –
Hypertension 0.631 (0.178–2.23) 0.475 – –
HDL-C 0.992 (0.938–1.05) 0.766 – –
LDL-C 1.01 (0.995–1.03) 0.150 – –
TG 1.00 (0.999–1.01) 0.106 – –
Hemoglobin A1c 1.26 (0.937–1.70) 0.126 – –
Previous statin therapy 0.583 (0.072–4.73) 0.613 – –
SBP on admission 1.01 (0.985–1.02) 0.638 – –
HR on admission 0.986 (0.954–1.02) 0.377 – –
Previous MI 3.31 (0.653–16.7) 0.149 – –
STEMI 1.45 (0.300–6.98) 0.646 – –
Preinfarction angina 1.91 (0.538–6.77) 0.317 – –
Anterior MI 1.57 (0.433–5.70) 0.492 – –
Killip class > I on admission 1.64 (0.410–6.56) 0.483 – –
Coronary multi-vessel involvement 0.703 (0.177–2.78) 0.615 – –
PG on admission 1.00 (0.995–1.01) 0.770 – –
WBC count on admission 1.00 (1.00–1.00) 0.671 – –
GFR on admission 1.01 (0.992–1.04) 0.195 – –
Hemoglobin on admission 1.38 (0.952–2.00) 0.0891 1.17 (0.771–1.77) 0.463
Stent diameter implanted at culprit lesion 0.881 (0.209–3.72) 0.863 – –
Stent length implanted at culprit lesion 1.01 (0.973–1.06) 0.519 – –
Current cigarette smoking 6.78 (1.41–32.6) 0.0169 5.35 (1.00–28.5) 0.0497

OR, odds ratio; CI, confidence interval; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; SBP,
systolic blood pressure; HR, heart rate; MI, myocardial infarction; STEMI, ST-elevation myocardial infarction; PG, plasma glucose; WBC, white blood cell; GFR, glomerular
filtration rate.

shown in Table 1. Cigarette smoking has been reported to affect
these lipid parameters, with studies showing that the plasma levels
of HDL-C were lower and TG higher in current smokers than in non-
smokers [21,22]. These lipid profiles were similar to those observed
in the “metabolic syndrome”, and suggest a mechanism by which
smoking may promote atherosclerosis. Previous reports have also
shown that the levels of inflammatory markers in the blood are
elevated in patients with the metabolic syndrome [23–25]. A pre-
vious study showed smokers had elevated levels of inflammatory
markers such as blood leukocyte count and plasma C-reactive pro-
tein level [21]. In addition, another study showed that an increased
WBC count on admission after AMI was associated with smok-
ing [26]. As we have shown in an experimental animal model
that chronic inflammation accompanied by the metabolic syn-
drome may be accelerated by myocardial ischemia-reperfusion, it
is possible that cigarette smoking may also exacerbate myocardial
ischemia-reperfusion injury and the prognosis of AMI [27]. In 978
patients with a first myocardial infarction, Robinson et al. reported
that the smokers had a larger infarct size as estimated by serum
CK concentrations (1382 IU/l versus 1146 IU/l, p = 0.010) [28]. In the
current study, the WBC count on admission was significantly higher
in current smokers than in the other two groups. In addition, there
was a tendency that current smokers had larger infarct size com-
pared to past smokers and non-smokers, and improvement in LVEF
was not observed only in current smokers. Moreover, there is a pos-
sibility that it may be associated with frequency of SAST in current
smokers. In this study, the prevalence of anterior MI was greater
in current smokers. Although a previous study demonstrated that
anterior MI was associated with adverse events after AMI, the high
incidence of anterior MIs in current smokers in the present study
was not related to adverse outcomes [29].
Although there is evidence that an elevated WBC count is
associated with a high risk of adverse events following an AMI,
the occurrence of heart failure in current smokers with a high
WBC count was not frequent compared to other groups. As older
age and anemia have been shown to be risk factors for adverse
cardiovascular events after AMI, the earlier onset of AMI and
increased hemoglobin level observed in current smokers may have
a cardioprotective effect in AMI patients, thereby improving prog-
nosis [30,31]. Although the phenomenon of “smoker’s paradox”
may be explained by the fact that current smokers are younger at
presentation, it is also necessary to take into account that levels
of inflammatory markers increase with age, despite the fact that
current smokers were significantly younger than non-smokers.
On the other hand, the incidence of SAST was significantly higher
in current smokers than in the other two groups. Multiple logistic
analysis showed that current smoking was an independent risk fac-
tor for SAST (OR 5.4; p < 0.05). The increased WBC count observed
in current smokers in the present study might appear to influence
the development of SAST through a hypercoagulable or throm-
boresistant state [32]. Another established mechanism underlying
SAST is platelet-mediated thrombosis due to arterial trauma [33].
Previous studies have shown that an increased platelet count, in
combination with elevated levels of C-reactive protein and fibrino-
gen, indicated an increased propensity to thrombosis in smokers
[34,35]. In addition, current smokers in our study had elevated
LDL-C levels compared with the other two groups. It has been
reported that an increased LDL-C level enhances platelet function
and increases the sensitivity of platelets to several naturally occur-
ring agonists [36]. As there is no other report that current smoking
increases the plasma level of LDL-C, it remains uncertain whether
this is a consistent finding. In contrast, increased platelet function
induced by current smoking in combination with elevated LDL-C
levels, may be associated with the occurrence of AMI and SAST.
As statins have been reported to have anti-thrombotic effects
[37,38], we carried out analyses to determine whether differences
in previous medical treatment (statins) affected the incidence of
SAST. However, in our study statin therapy administered either on
or after admission was not associated with SAST.
All of the current smokers in this study quitted smoking after
admission for AMI. We defined current smokers as individuals
who had smoked any tobacco products in the previous 12 months,
 T. Honda et al. / Journal of Cardiology 63 (2014) 358–364
including those who had quit within the past year, because past
studies reported that smoking cessation might attenuate activa-
tion of inflammation and hemostasis 2–12 months later [39], and
most inflammatory and hemostatic levels improved within 5 years
of smoking cessation but took over 20 years to revert to levels of
non-smokers [40]. These findings were compatible with the present
study showing that the risk of SAST in current smokers did not
reduce immediately after smoking cessation.
The present study excluded patients treated with DESs as
the number of patients was too small to analyze the association
between current smoking and SAST after AMI. In addition, as we
excluded patients who did not undergo a follow-up examination,
the study did not include patients who died during hospitaliza-
tion. It therefore remains uncertain whether current smoking is
associated with in-hospital death.
Conclusions
This study demonstrated that current cigarette smoking was an
independent risk factor for SAST, although it was not associated
with adverse outcomes in AMI patients. It is therefore important
to pay attention to the high-risk group for SAST, especially current
smokers after a primary PCI for AMI.
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