論文の公開元へSmoking status and endothelial function in Japanese men
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Journal : SREP 41598
Article No : 80012
Author’s Response
Pages : 1
MS Code : 80012
Dispatch : 17-12-2020
www.nature.com/scientificreports
OPEN
Smoking status and endothelial
function in Japanese men
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Haruki Hashimoto1, Tatsuya Maruhashi1, Takayuki Yamaji1, Takahiro Harada1, Yiming Han1,
Yuji Takaeko1, Yasuki Kihara1, Kazuaki Chayama2, Chikara Goto3, Yoshiki Aibara4,
Farina Mohamad Yusoff4, Shinji Kishimoto4, Masato Kajikawa4, Ayumu Nakashima5 &
Yukihito Higashi4,6*
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It is established that smoking is a major risk factor of atherosclerosis. Endothelial dysfunction occurs
in the initial step in the pathogenesis of atherosclerosis and plays a critical role in the development
of atherosclerosis. The purpose of this study was to evaluate the association between smoking
status and endothelial function in detail in men. We measured flow-mediated vasodilation (FMD) in
2209 Japanese men including 1181 men who had never smoked and 1028 current smokers. All of the
participants were divided into five groups by smoking pack-years: never smoker group (= 0), light
smoker group (> 0 to 10), moderate smoker group (> 10 to 20), heavy smoker group (> 20 to 30) and
excessive smoker group (> 30). FMD significantly decreased in relation to pack-years (6.6 ± 3.4% in the
never smoker group, 6.8 ± 3.0% in the light smoker group, 6.5 ± 2.9% in the moderate smoker group,
5.9 ± 2.9% in the heavy smoker group, and 4.9 ± 2.7% in the excessive smoker group; P < 0.001). After
adjustment for age (≥ 65 years), body mass index, systolic blood pressure, low-density lipoprotein
cholesterol, glucose, and year of recruitment, FMD was significantly smaller in the excessive smoker
group than in the never smoker group as a reference group (OR 1.95, 95% CI 1.42 to 2.67; P < 0.001).
These findings suggest that FMD decreases with an increase in the number of cigarettes smoked and
that excessive smoking is associated with endothelial dysfunction. Cigarette smoking is harmful to
vascular function in men who are heavy smokers.
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Cigarette smoking kills over five million people worldwide every year despite the fact that cigarette control
policies have been implemented and the prevalence of smoking has declined in many countries1. It has been
reported that approximately 10% of all the adult deaths from cardiovascular diseases are attributed to cigarette
use2. Smoking per se is a major risk factor of atherosclerosis3. It is thought that smoking plays a critical role in
the maintenance and development of atherosclerosis through an increase in low-density lipoprotein cholesterol
levels, decrease in high-density lipoprotein cholesterol level, increase in catecholamine level, increase in the
amount of fibrinogen, increase in reactive oxygen species (ROS), enhancement of platelet aggregation, increase
in insulin resistance, and activation of Rho-associated kinase4–6.
Endothelial dysfunction occurs in the initial step in the pathogenesis of atherosclerosis and plays a critical role
in the development of atherosclerosis7,8. Traditional cardiovascular risk factors are associated with endothelial
dysfunction. It is thought that smoking also plays a critical role in the pathogenesis and development of atherosclerosis by, at least in part, endothelial dysfunction. Several investigations, including us, have clearly shown
that smoking impairs endothelial function6,9–11. In addition, it has been shown that smoking is an independent
predictor for endothelial dysfunction. However, the relationship between smoking status and endothelial function has not been shown in detail. How much does smoking affect endothelial function?
Recently, measurement of flow-mediated vasodilation (FMD) in the brachial artery has been widely used for
assessing endothelial function in humans12–15. Measurement of FMD is useful for assessment of atherosclerosis
1
Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima
University, Hiroshima, Japan. 2Department of Gastroenterology and Metabolism, Institute of Biomedical
and Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima,
Japan. 3Hiroshima International University, Hiroshima, Japan. 4Department of Cardiovascular Regeneration
and Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3
Kasumi, Minami-ku, Hiroshima 734-8551, Japan. 5Department of Stem Cell Biology and Medicine, Hiroshima
University Graduate School of Biomedical Sciences, Hiroshima, Japan. 6Division of Regeneration and Medicine,
Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. *email:
yhigashi@hiroshima-u.ac.jp
Scientific Reports | _#####################_ | https://doi.org/10.1038/s41598-020-80012-x
Journal : SREP 41598
Article No : 80012
Pages : 8
MS Code : 80012
1
Dispatch : 17-12-2020
ol.:(
)
www.nature.com/scientificreports/
P value
Variables
Total (n = 2209)
Never smoker (n = 1181)
Current smoker (n = 1028)
Age, y
48 ± 14
47 ± 16
50 ± 12
Body mass index, kg/m2
23.4 ± 3.5
23.3 ± 3.5
23.6 ± 3.6
0.01
Systolic blood pressure, mmHg
128 ± 16
127 ± 15
129 ± 17
< 0.001
< 0.001
< 0.001
Diastolic blood pressure, mmHg
79 ± 12
77 ± 12
81 ± 12
Heart rate, bpm
65 ± 12
65 ± 12
65 ± 11
0.33
Total cholesterol, mmol/L
5.04 ± 0.88
5.04 ± 0.88
5.04 ± 0.88
0.82
Triglycerides, mmol/L
1.35 ± 0.71
1.24 ± 0.64
1.47 ± 0.76
< 0.001
HDL cholesterol, mmol/L
1.45 ± 0.39
1.53 ± 0.39
1.40 ± 0.36
< 0.001
LDL cholesterol, mmol/L
2.97 ± 0.80
2.97 ± 0.80
2.97 ± 0.83
0.86
Glucose, mmol/L
5.72 ± 1.44
5.66 ± 1.44
5.77 ± 1.44
< 0.001
HbA1c, %
5.7 ± 0.7
5.6 ± 0.8
5.7 ± .0.7
0.23
Medical history, n (%)
487 (41.2)
510 (43.2)
Diabetes mellitus
262 (11.9)
120 (10.2)
Previous cardiovascular and cerebrovascular
disease
250 (11.3)
131 (11.1)
486 (47.3)
0.005
549 (53.4)
< 0.001
142 (13.8)
0.008
119 (11.6)
0.74
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973 (44.1)
1059 (47.9)
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Hypertension
Dyslipidemia
Table 1. Clinical characteristics of never and current smokers in men. All results are presented as mean ± SD.
HDL, high-density lipoprotein; LDL, low-density lipoprotein.
− 0.40
Body mass index, kg/m2
− 0.22
P value
95% CI
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r
Age, y
− 0.44
− 0.37
− 0.26
− 0.18
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Variables
Systolic blood pressure, mmHg
− 0.21
− 0.25
− 0.17
< 0.001
< 0.001
< 0.001
Diastolic blood pressure, mmHg
− 0.14
− 0.18
− 0.09
< 0.001
Heart rate, bpm
− 0.05
− 0.09
− 0.01
0.03
0.04
Total cholesterol, mmol/L
0.00
0.09
− 0.17
− 0.21
− 0.13
< 0.001
HDL cholesterol, mmol/L
0.11
0.07
0.15
< 0.001
0.04
EC
0.04
Triglycerides, mmol/L
0.04
0.00
0.09
− 0.29
− 0.32
− 0.25
< 0.001
HbA1c, %
− 0.16
− 0.20
− 0.12
< 0.001
Smoking, pack-years
− 0.16
− 0.20
− 0.12
< 0.001
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LDL cholesterol, mmol/L
Glucose, mmol/L
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Table 2. Univariate analysis of the relation between FMD and variables in never smokers and current
smokers of men. HDL, indicates high-density lipoprotein; LDL, low-density lipoprotein; FMD, flow-mediated
vasodilation; 95% CI 95% confidence interval.
from the early stage to end stage of. It has been shown that FMD is an independent predictor of cardiovascular
outcomes16.
In the present study, we evaluated the association of smoking status with endothelial function assessed by
FMD in men.
Results
Relationship between smoking and endothelial function in current smokers in men. We evaluated the relationship between smoking and endothelial function in current smokers in men. The characteristics
of 2209 subjects (1181 men who had never smoked and 1028 current smokers) are summarized in Table 1. The
mean value of FMD in the 2209 subjects was 6.2 ± 3.2%. FMD was significantly smaller in current smokers than
in men who had never smoked (5.9 ± 2.9% vs. 6.6 ± 3.4%, P < 0.001).
Univariate analysis revealed that pack-years was significantly correlated with FMD (r = -0.16, P < 0.001)
(Table 2 and Fig. 1). After adjustment for age, body mass index (BMI), systolic blood pressure, low-density lipoprotein cholesterol, glucose, and year of recruitment, the association between pack-years and FMD (β = -0.07,
P < 0.001) was significant (Table 3).
The clinical characteristics of men who had never smoked and current smokers categorized according to
smoking pack-years are summarized in Table 4. ...
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