Journal Pone 0202977
Journal Pone 0202977
Funding: Funded by National Health Research hazards on CVD. In a meta-analysis of 603,838 individuals, long working hours (55 hours
Institutes of Taiwan (98-EO-PP01, 99-EO-PP01, per week) were associated with a 13% increase in coronary heart disease risk and a 33%
00-EO-PP01, EO-101-PP-01, EO-102-PP-01 and
increase in stroke risk [1]. In the Nurses’ Health Study, rotating night shift work was associated
EO-103-PP-01) to Dr. Saou-Hsing Liou National
Institute of Occupational Safety and Health, Japan with a 4% increased risk of ischemic stroke for every 5 years[2]. Previously, 13 European epide-
(IOSH96-M102 and IOSH97-M102) to Dr. Saou- miologic cohort studies had reported that the association between job strain and coronary
Hsing Liou. heart disease was significant for men and women, including those younger and older than 50
Competing interests: The authors have declared years of age, and at all levels of socioeconomic status[3]. Based on abovementioned evidence,
that no competing interests exist. overwork was a multifactorial, work-related psychosocial factor that interacted with environ-
mental and lifestyle factors to cause CVD or karoshi. In the transportation industry, concur-
rent individual risk factors and work environmental risk factors among professional drivers
contributed to cumulative CVD impact, such as age, metabolic syndrome, smoking, sedentary
work, unconventional and irregular hours, shift work, long working hours, a tight delivery
schedule, and job strain. Among approximately 120,000 Japanese workers from a national rep-
resentative insurance organization, several business categories, including transportation, con-
struction, and mining had the highest prevalence for metabolic syndrome (MetS) at 25.7%,
21.0%, and 20.5%, respectively[4]. Among them, metabolic Syndrome (MetS) is a cluster of
metabolic abnormalities and is considered as a multi-morbid condition.
Metabolic syndrome (MetS), characterized by central obesity, glucose intolerance, athero-
genic dyslipidemia, and fluctuations in blood pressure, was strongly associated with increased
risk of coronary heart disease, cerebrovascular diseases, diabetes, and mortality[5, 6]. Patients
with MetS were associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold
increase in all-cause mortality compared with those without MetS[7]. Moreover, previous Nor-
wegian HUNT Study mentioned that the association between metabolic syndrome and the
risk of death from cardiovascular disease was stronger among persons with sedentary work
and physically heavy work compared with persons with a lot of walking/lifting at work[8].
These findings implied that occupational physical activity or job categories may moderate the
detrimental effects of MetS on CVD. Despite the tight link between MetS and CVD risk, little
empirical evidence had been found that the psychosocial factors in workplace play which role
in the development of MetS and CVD.
Importantly, light could be shed on psychosocial risks in workplace which was still largely
uninvestigated. Therefore, studies on whether or not psychosocial factors contributes to or
exacerbates CVD with/without MetS, could support a novel target for cardiovascular risk
reduction in bus drivers. Thus, we performed a perspective cohort study to investigate the
interaction of occupational psychosocial hazards with the risk of CVD among drivers with
MetS.
Methods
Ethics statement
Our study protocol was approved by the institutional review board (IRB) of the National
Health Research Institutes and Tri-Service General Hospital in accordance with the revised
Helsinki Declaration. All subjects completed consent forms and agreed to participate in the
survey after a detailed explanation of the protocol of the study.
Study population
A total of 1,650 professional drivers from a largest transportation company were recruited in
the Taiwan Bus Driver Cohort Study (TBDCS). After completion of informed consents, all
participants received the basic and working related questionnaire and biochemistry tests. This
cohort was linked to the Driving Hours Dataset during the period from 2005 to 2007[9]. At
baseline, all 1,650 eligible drivers were followed up at the time of the evaluation and received
comprehensive examinations. Our exclusion criteria included previous CVD history (n = 85),
driving days < 100 days (n = 613), missing information on demographics (n = 23), and bio-
chemical examinations (n = 222). To ensure some homogeneity of social background, all sub-
jects were selected from the same bus company. Finally, 707 eligible drivers were followed up
from 2005 to 2012.
discomfort, lack of motivation, and sleepiness[18]. The participants scores their perceived
intensity of fatigue based on 25 items.
Sociodemographic variables
All eligible subjects were interviewed using a structured questionnaire, including questions
regarding demographics (age, marital status, and education status), work conditions (work
hours, years of driving experience, frequency of driving more than 12 hours a day, and schedule
of rotating shifts), lifestyle habits (smoking, betel nut chewing, and drinking), and past medical
histories. Long working hours were analyzed as a categorical variable (driving hours more than
12 hour/day and less than or equal to 12 hour/day). Body weight and height were evaluated
using a digital scale, and BMI level was calculated as the subject’s weight in kilograms divided
by the square of their height in meters (kg/m2). We used a digital automatic sphygmomanome-
ter to measure systolic and diastolic blood pressure in a sitting position after 10 to 15 minutes of
rest. The blood testing was collected after 8 to 10 hours of overnight fasting to determine serum
levels of high-density lipoprotein cholesterol, triglyceride and fasting blood glucose.
Outcome measures
Each eligible subject was traced from the date of the baseline evaluation to the development of
CVD or the end of the follow-up. The primary endpoint in our study was incident CVD,
including ischemic heart disease, congestive heart failure, dissecting aneurysm of the aorta,
serious cardiac arrhythmia, and cerebrovascular disease (ICD9: 390–459 and ICD10: I00-I99)
based on the recognition criteria for overwork-related CVD in Taiwan [19, 20].
Statistical analysis
All statistical analyses were examined using SPSS (Version 18.0 for Windows, SPSS, Inc., Chi-
cago, IL, USA). Two-sided P-values < 0.05 were used to indicate significant differences. Con-
cerning the association analysis, Cox proportional hazards regression was used to investigate
the hazard ratios (HRs) for cardiovascular and cerebrovascular disease incidence. The poten-
tial confounders adjusted in the HRs analysis included age, BMI, education, drinking, smok-
ing, and exercise. Five models were used to clarify the correlations among metabolic
syndrome, work-related factors, and CVD incidences. Dichotomized occupational psychoso-
cial hazards in theses analyses were long working hour (driving hour>12 hour/day vs 12
hour/day), high job stress (SSOS score < +2 vs +2), and high fatigue (SOFI 3.5 vs < 3.5). The
five models analyzed include: Model 1: a single occupational psychosocial hazard was investi-
gated for CVD incidences; Model 2: long working hours and high job stress were investigated
for CVD incidence; Model 3: long working hours and high fatigue were investigated for CVD
incidence; Model 4: high job stress and high fatigue were investigated for CVD incidences.
Model 5: three variables, including long working hours, high job stress, and high fatigue, were
investigated for CVD incidence. Finally, sensitivity analyses were performed to determine the
robustness of the findings using different exclusion criteria. In the sensitivity analyses (S1 and
S2 Tables) of 778 drivers, the exclusion definition of previous CVD history did not include
hypertension (n = 71).
Results
Baseline characteristics
Demographic characteristics and biochemical indices were presented in Table 1. At study
baseline, there were 327 drivers with MetS and 380 drivers without MetS (Non-MetS). The
Table 1. Demographic characteristics and biochemical indices among bus drivers and stratified by metabolic syndrome (n = 707).
Variables All drivers (N = 707) MetS (N = 327) Non-MetS (N = 380) p-value
Continuous variables
Age (years), mean (SD) 43.5 (6.9) 43.8 (6.5) 43.2 (7.2) 0.285
BMI (kg/m2), mean (SD) 26.1 (4.0) 28.4 (3.8) 24.1 (3.0) <0.001
Systolic blood pressure (mmHg), mean (SD) 126.9 (13.1) 132.2 (12.2) 122.4 (12.1) <0.001
Diastolic blood pressure (mmHg), mean (SD) 80.9 (10.3) 85.1 (10.0) 77.3 (9.1) <0.001
Total cholesterol (mg/dl), mean (SD) 203.5 (38.0) 210.1 (38.0) 197.8 (37.1) <0.001
Triglyceride (mg/dl), mean (SD) 209.9 (181.3) 287.1 (226.0) 143.6 (87.9) <0.001
HDL cholesterol (mg/dl), mean (SD) 37.7 (9.3) 33.6 (7.0) 41.2 (9.7) <0.001
Fasting blood glucose (mg/dl), mean (SD) 102.7 (41.5) 115.2 (53.2) 91.9 (22.7) <0.001
Categorical variables
CVD after follow-up 0.012
Yes 77(10.9) 46(14.1) 31(8.2)
No 630(90.1) 281(85.9) 349(91.8)
Marital status, n (%) 0.899
Unmarried 123 (17.4) 59 (18.0) 64 (16.8)
Married 506 (71.2) 233 (71.3) 273 (71.8)
Others 78 (11.4) 35 (10.7) 43 (11.4)
Education, n (%) 0.563
Junior high school 206 (29.1) 93 (28.4) 113 (29.7)
Senior high and vocational school 451 (63.8) 214 (65.4) 237 (62.4)
University and College 50 (7.1) 20 (6.2) 30 (7.9)
Cigarette smoking, n (%) 0.033
Never smokers 241 (34.1) 99 (30.3) 142 (37.4)
Ex-smokers 47 (6.6) 17 (5.2) 30 (7.9)
Current smokers 414 (59.3) 207 (64.5) 207 (54.7)
Missing n = 5
Alcohol use, n (%) 0.489
No 557 (82.4) 253 (77.4) 304 (80.0)
Yes 146 (17.6) 71 (22.6) 75 (20.0)
Missing n = 4
Betel nut chewing 0.110
No 583 (82.5) 262 (80.1) 321 (84.5)
Yes 123 (17.5) 65 (19.9) 58 (15.5)
Missing n = 1
Moderate exercise, n (%) 0.159
No 516 (72.9) 248 (75.8) 268 (70.5)
Yes 181 (27.1) 76 (24.2) 105 (29.5)
Missing n = 10
Working hour, n (%) 0.134
12 hr 424 (59.9) 186 (56.9) 238 (62.6)
> 12 hr 278 (40.1) 138 (43.1) 140 (37.4)
Missing n = 5
SSOS, n (%) 0.966
+ 2 ~ +1 161 (22.8) 66 (20.2) 95 (25.0)
-2 ~ 0 544 (77.2) 261 (79.8) 283 (75.0)
Missing n = 2
SOFI, n (%) 0.610
(Continued)
Table 1. (Continued)
SD, standard deviation; MetS, metabolic syndrome; BMI, body mass index; HDL, high-density lipoprotein; SSOS, Stress Satisfaction Offset Score; SOFI, Swedish
Occupational Fatigue Inventory
https://doi.org/10.1371/journal.pone.0202977.t001
mean age of participants with MetS and Non-MetS was 43.8 and 43.2 years old, respectively.
With comparison to participants with non-MetS, participants with MetS were older and had
higher mean BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycer-
ide, and fasting blood glucose.
Table 2. Unadjusted and adjusted hazard ratios of work patterns and psychosocial hazards on CVD in bus drivers (n = 707).
Univariate Analysis Multivariate Analysis a.
b
Independent variables HR 95% CI p-value HR 95% CI p-value
1 Metabolic syndrome (Ref.< No)
Yes 1.77 1.12 2.79 0.014 1.38 0.80 2.36 0.247
2 Long working hours (Ref. Working hour 12 hour/ day)
Working hour >12 hour/ day 1.93 1.23 3.02 0.004 1.76 1.11 2.79 0.016
3 Shift work (Ref. No shift work)
Shift work 0.74 0.43 1.28 0.281 0.68 0.39 1.18 0.172
4 Job Content Questionnaire (Ref. Low strain)
High strain 1.17 0.71 1.94 0.538 1.08 0.65 1.80 0.772
5 Stress Satisfaction Offset Score (Ref. = +2~+1)
-2 ~ 0 1.38 0.78 2.42 0.270 1.20 0.67 2.14 0.539
6 Swedish Occupational Fatigue Inventory (Ref. <3)
>=3 1.51 0.95 2.39 0.080 1.58 0.98 2.55 0.060
CVD, cardiovascular and cerebrovascular diseases; HR, hazard ratios; CI, confidence interval; BMI, body mass index.
a.
Adjusted for age, BMI, education, drinking, smoking, and exercise.
b.
Each independent variable (1–6) was solely included in the models
https://doi.org/10.1371/journal.pone.0202977.t002
Table 3. Hazard ratios f of interactions among psychosocial hazards or on CVD classified by psychosocial hazards in participants (n = 707).
Dependent variable Univariate Analysis Multivariate Analysis
Model 1 HR 95%CI p-value HR 95%CI p-value
Long working hours 1.76 1.11 2.81 0.017 1.65 1.03 2.66 0.037
High job stress 1.03 0.56 1.87 0.936 0.94 0.51 1.74 0.852
High fatigue 1.31 0.81 2.12 0.280 1.43 0.87 2.36 0.160
MetS 1.69 1.07 2.67 0.025 1.33 0.77 2.29 0.308
Model 2
Ref: Working hours < = 12 hrs and SSOS = +2
Either long working hours or high job stress only 1.80 0.83 3.89 0.135 1.64 0.76 3.57 0.210
Both long working hours and high job stress 2.48 1.14 5.37 0.022 2.17 0.99 4.79 0.054
MetS 1.69 1.07 2.67 0.025 1.33 0.77 2.30 0.302
Model 3
Ref: Working hours < = 12 hr & SOFI<3
Either long working hours or high fatigue only 1.27 0.71 2.28 0.419 1.35 0.75 2.43 0.321
Both long working hours and high fatigue 2.29 1.28 4.09 0.005 2.31 1.26 4.23 0.007
MetS 1.69 1.07 2.67 0.025 1.32 0.77 2.26 0.321
Model 4
Ref: SSOS = +2 & SOFI<3
Either high job stress or high fatigue only 2.10 0.92 4.77 0.078 1.90 0.83 4.35 0.130
Both high job stress and high fatigue 2.15 0.96 4.83 0.064 2.07 0.90 4.73 0.086
MetS 1.70 1.08 2.69 0.022 1.32 0.76 2.27 0.321
Model 5
Ref: Working hours < = 12 hr & SSOS = +2 & SOFI<3
One of three variables (long working hours, high job stress, or high fatigue) 2.76 0.95 8.02 0.062 2.43 0.83 7.08 0.105
Two of three variables (long working hours, high job stress, or high fatigue) 2.66 0.92 7.67 0.070 2.57 0.89 7.45 0.082
All of three variables (long working hours, high job stress, or high fatigue) 4.10 1.42 11.80 0.009 3.71 1.26 10.91 0.017
MetS 1.69 1.07 2.67 0.025 1.31 0.76 2.26 0.331
Long working hours = driving hour>12 hour/ day; High job stress = SSOS_scores < +1; High fatigue = SOFI > = 3.
CVD, cardiovascular and cerebrovascular diseases; HR, hazard ratios; CI, confidence interval; MetS, metabolic syndrome; SSOS, Stress Satisfaction Offset Score; SOFI,
Swedish Occupational Fatigue Inventory.
a.
Adjusted for age, BMI, education, drinking, smoking, and exercise.
https://doi.org/10.1371/journal.pone.0202977.t003
Table 4. Combinations of individual psychosocial hazards and metabolic syndrome for predicting CVD (n = 707).
Univariate Analysis Multivariate Analysis a.
Combinations LWH HJS HF MetS HR 95%CI p-value HR 95%CI p-value
1 - - - - Reference Reference
2 + - - - 2.95 0.49 17.66 0.237 2.38 0.39 14.66 0.349
3 - + - 1.38 0.33 5.78 0.662 1.22 0.29 5.20 0.788
4 - - + - 1.74 0.29 10.49 0.544 1.99 0.33 12.15 0.458
5 + + - 0.61 0.06 5.83 0.664 0.66 0.07 6.42 0.721
6 - + + - 2.27 0.60 8.63 0.227 2.31 0.60 8.91 0.223
7 + + - 6.75 0.70 65.09 0.099 6.94 0.69 69.77 0.100
8 + + + - 2.58 0.69 9.62 0.158 2.46 0.64 9.43 0.190
9 + - - + 2.53 0.26 24.37 0.422 2.19 0.23 21.38 0.499
10 - + - + 3.45 0.95 12.60 0.061 2.62 0.69 9.95 0.158
11 - - + + 3.56 0.59 21.33 0.165 2.97 0.48 18.28 0.241
12 + + - + 4.46 1.15 17.29 0.031 3.24 0.80 13.14 0.100
13 - + + + 1.48 0.35 6.20 0.595 1.30 0.30 5.60 0.723
14 + - + + 12.01 2.39 60.43 0.003 10.91 2.11 56.30 0.004
15 + + + + 4.76 1.39 16.34 0.013 3.72 1.02 13.56 0.046
LWH, long working hours; HJS, high job stress; HF, high fatigue; MetS, metabolic syndrome
a.
Adjusted for age, BMI, education, drinking, smoking, and exercise.
https://doi.org/10.1371/journal.pone.0202977.t004
CI = 1.26–10.91, P value = 0.017), respectively, which were higher than the HRs of participants
with two psychosocial hazards. Our results still remained robust to sensitivity analyses using the
different exclusion definitions (S1 Table).
In the Table 4, we showed the different combinations of individual psychosocial hazards
and metabolic syndrome for predicting CVD. Compared with those without any psychosocial
hazards, there were no significant associations with CVD among non-MetS participants with
1–3 occupational psychosocial hazards. Notably, multivariate analysis HRs of MetS partici-
pants with two (long working hours+ high fatigue) and three occupational psychosocial haz-
ards were 10.91 (95% CI = 1.02–56.30, P value = 0.004) and 3.72 (95% CI = 1.02–13.56, P
value = 0.046), respectively. In the sensitivity analyses (S2 Table), our results were still robust
to using the different exclusion definitions.
Discussion
To the best of our knowledge, our study was the first investigation to examine the combined effect
of metabolic syndrome and occupational psychosocial hazards on the risk of CVD. Thus, we
sought to describe an approach to evaluate the status of overwork using by multiple clustered
traits. In this 8-year longitudinal cohort study, we found that the risk of CVD was highest among
the MetS participants who had long working hours, high job stress, and high fatigue. However, no
evidence of associations between occupational psychosocial hazards and CVD was observed in
the subjects without MetS. There was a linear increase in the HR among MetS participants with
increased numbers of occupational psychosocial hazards. Among three occupational psychosocial
hazards, long working hours were most associated with an elevated risk of CVD.
For detrimental effect of long working hours, our study finding was concordant with the
findings of several previous studies. The results from several prospective observational studies
suggested an approximately 40% increase in the risk of CHD among employees with long
working hours[21]. In a systematic review of epidemiological evidence, long working hours
had significant adverse effects on many health outcomes, including depressive state, anxiety,
sleep condition, and coronary heart disease[22]. Moreover, employees who work long hours
have an elevated risk of stroke than those who work standard hours[1]. There was one plausi-
ble explanation for this. Sleep deprivation and fragmentation caused by long working hours
increased the risk of type 2 diabetes through β-cell dysfunction and insulin resistance, indi-
rectly leading to accelerate insult to vascular endothelial cells and an increased risk of CVD
[23].
High job stress was linked with a broader spectrum of diseases via an unhealthy lifestyle
and obesity, including type 2 diabetes, coronary heart disease, and stroke[24, 25]. Meta-analy-
sis of individual participant data from over 47,000 participants showed that the association
between job strain and elevated cardiovascular risks was attributable to the higher prevalence
of diabetes, smoking, and physical inactivity among those reporting job strains[26]. In the
cross-sectional data of 46,573 Finnish public sector employees, an association between higher
work stress and lower leisure time physical activity was observed[27]. High stress attenuated
the willingness or the ability of employees to engage in regular exercise and other physical
activity[28]. Another possible pathophysiological mechanism underlying the association
between job strain and CVD was attributed to an imbalance of the autonomic nervous system
and elevated catecholamines. Emerging evidence had shown that high strain jobs were
reported to be significantly associated with decreased vagal tone indicators[29, 30]. It was sug-
gested that reduced activity of the parasympathetic nervous system increased the risk of coro-
nary heart disease[31].
In terms of high fatigue, MetS participants with high fatigue had a higher risk of CVD com-
pared with those without three occupational psychosocial hazards. Consistent with our find-
ings, Appels et al observed that undue fatigue was a frequent premonitory symptom of cardiac
events. They delineated a triad of symptoms as vital exhaustion (VE) or exhaustion, including
excessive fatigue, feelings of demoralization, and increased irritability[32]. In a meta-analysis
of 17 studies concerning VE/exhaustion, a significant association between VE/exhaustion and
CVD events remained after adjusting for a number of clinical and psychosocial factors[33].
The psychosocial consequences of fatigue were becoming increasingly addressed because high
levels of fatigue, as measured by the Short Form 36 vitality domain, were associated with
increased mortality in the general population[34]. Collectively, it was possible that fatigue or
VE/exhaustion was a potential underlying psychophysiological mediator of CVD.
Even through this body of research had the undeniable merit of offering valuable insights
into the interaction between MetS and psychosocial hazards, it also some limitations. The first
limitation concerned the assessments used in the current study. Although there were many
work-related psychosocial hazards that had a substantial impact on CVD outcomes, we tried
to adopted several valuable questionnaires to evaluate these hazards. Second, the generalizabil-
ity of the results to other populations with different occupations may be limited since all partic-
ipants in the present study were drivers. Third, the interaction between MetS and changes in
psychosocial hazards over time was not analyzed, because the pertinent variables were mea-
sured only once at enrollment into the study. Last, all measures were only taken once at base-
line but not repeated measures during follow-up period. Moreover, the interpretation of our
observations was limited because of absence of long-term changes in psychosocial hazards and
cardiometabolic risks.
Conclusion
Our findings clearly supported the notion that a combination of long working hours, high job
stress, and high fatigue in MetS participants increased the risk of developing CVD. These
Supporting information
S1 Table. Hazard ratios f of interactions among psychosocial hazards or on CVD classified
by psychosocial hazards in participants.
(DOCX)
S2 Table. Combinations of individual psychosocial hazards and metabolic syndrome for
predicting CVD.
(DOCX)
Author Contributions
Conceptualization: Wei-Liang Chen, Wei-Te Wu, Saou-Hsing Liou.
Data curation: Wei-Liang Chen, Chung-Ching Wang, Sheng-Ta Chiang, Ying-Chuan Wang,
Yu-Shan Sun, Wei-Te Wu, Saou-Hsing Liou.
Formal analysis: Wei-Liang Chen, Chung-Ching Wang, Sheng-Ta Chiang, Ying-Chuan
Wang, Yu-Shan Sun, Wei-Te Wu, Saou-Hsing Liou.
Funding acquisition: Saou-Hsing Liou.
Investigation: Wei-Liang Chen, Chung-Ching Wang, Sheng-Ta Chiang, Ying-Chuan Wang,
Yu-Shan Sun, Wei-Te Wu, Saou-Hsing Liou.
Methodology: Wei-Liang Chen, Chung-Ching Wang, Sheng-Ta Chiang, Ying-Chuan Wang,
Yu-Shan Sun, Wei-Te Wu, Saou-Hsing Liou.
Project administration: Wei-Liang Chen, Chung-Ching Wang, Sheng-Ta Chiang, Ying-
Chuan Wang, Yu-Shan Sun, Wei-Te Wu, Saou-Hsing Liou.
Resources: Wei-Liang Chen.
Supervision: Wei-Te Wu, Saou-Hsing Liou.
Validation: Wei-Liang Chen, Wei-Te Wu, Saou-Hsing Liou.
Visualization: Wei-Liang Chen, Wei-Te Wu, Saou-Hsing Liou.
Writing – original draft: Wei-Liang Chen.
Writing – review & editing: Wei-Liang Chen, Wei-Te Wu, Saou-Hsing Liou.
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