Introduction

The high prevalence of cardiovascular diseases (CVDs) among professional drivers is not only a health problem but also a social problem as it is a cause of disease-related traffic accidents [1, 2]. Hypertension is one of the most serious risk factors for CVDs [3]. Therefore, taking measures against hypertension is of paramount importance to prevent CVDs.

Several epidemiological studies have demonstrated that sleep-disordered breathing (SDB) is a risk factor for hypertension [4,5,6,7,8,9,10] and is associated with the incidence of CVDs, such as myocardial infarction, heart failure, and stroke [11,12,13]. Our recent study has also shown that SDB is associated with elevated central systolic blood pressure, which is a better predictor of future CVDs than brachial blood pressure [14]. These findings suggest that early detection and treatment of SDB is important in the overall management of hypertension [15]. On the other hand, alcohol consumption is also known to be a major risk factor for hypertension [16,17,18,19,20] and is also related to severe hypoxemia and severe SDB [21,22,23,24].

Although both SDB and alcohol consumption are associated with hypertension, the combined effects of alcohol consumption and SDB on hypertension remain unknown. We hypothesized that the combination of alcohol consumption and SDB would have a more harmful effect on the development of hypertension than either factor alone. To test this hypothesis, we investigated the combined effects of SDB and alcohol consumption on hypertension among Japanese male bus drivers.

Methods

Study population

This cross-sectional study was conducted between September 2013 and the end of September 2016, and all participants were recruited on a voluntary basis from 222 bus operating companies in 10 prefectures. The participants comprised mainly members of the Nihon Bus Association in Japan. Of the 4443 participants aged 20–82 years, all females (298 in total) were excluded due to the relatively small number compared to the number of males. In addition, 246 participants who were ≥66 years old and individuals lacking past data on SDB (n = 345), alcohol consumption (n = 235), and blood pressure (n = 708) were also excluded. The remaining 2525 men aged 20–65 years formed the study subjects. The study protocol was approved by the Ethics Review Board of Juntendo University Faculty of Medicine, and informed consent was obtained from each study participant.

Data collection

We collected a self-administered questionnaire to obtain information on systolic blood pressure (SBP), diastolic blood pressure (DBP), and use of antihypertensive medications from each participant. Participants were asked to “fill in their recent blood pressure levels,” and they filled in their numerical SBP and DBP values. Hypertension was defined as SBP ≥ 140 mmHg, DBP ≥ 90 mmHg and/or use of antihypertensive medications. Alcohol consumption was also assessed by a self-administered questionnaire. Participants were asked about the average amount of alcohol they drink per day over 1 week. Alcohol consumption was assessed in units of “go”, a Japanese unit of volume corresponding to 23 g ethanol, which was then converted to grams of ethanol per day. One “go” is equivalent to 180 ml of sake and corresponds to one bottle (633 ml) of beer, two single shots (75 ml) of whiskey, or two glasses (180 ml) of wine. It was then converted to grams of alcohol per body weight (kg). The study subjects were classified according to the amount of alcohol consumption into four groups: nondrinker group, <0.5 g/day/kg body weight group, 0.5 to <1.0 g/day/kg body weight group, and ≥1.0 g/day/kg body weight group, using the classification system of Tanigawa and colleagues [22].

Assessment of sleep-disordered breathing

SDB was evaluated noninvasively using a portable single-channel airflow monitor with the attached flow thermocouple sensor (SOMNIE; NGK Spark Plug, Nagoya, Japan). The device automatically measures the flow respiratory disturbance index (RDI), defined as the number of respiratory disturbance events per hour. Each subject was provided with instructions on the use of the monitor and the recording of breathing over the entire night at home [25, 26]. RDI is more sensitive than the oxygen desaturation index, and previous studies reported that RDI correlates with the apnea–hypopnea index (AHI) assessed by concurrent polysomnography (PSG) [25, 26]. The criterion for SDB was RDI levels of 10 and 20 events per hour, based on the findings that these RDI cutoffs represented AHIs of ≥5 and ≥15 events per hour, respectively, as determined by PSG, with corresponding sensitivities of 0.96 and 0.91 and specificities of 0.82 and 0.82 [25, 26].

Covariates

Age, height, weight and the number of cigarettes smoked per day were assessed by self-administered questionnaires. Body mass index (BMI) was calculated as weight (kg) divided by the square of height in m2. Smoking status was classified into three categories: nonsmokers, 1–20, or ≥21 cigarettes per day. Current smokers were defined as individuals who smoked ≥1 cigarette/day.

Statistical analysis

The mean values of age, BMI, alcohol consumption, SBP and DBP; median RDI; and proportion of current smokers and individuals with hypertension were calculated according to the categories of alcohol consumption and RDI. Trend tests were performed by simple regression analysis and the chi-square test. Multivariable logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of hypertension, according to the categories of RDI and alcohol consumption. A linear trend was tested using the median values of RDI and alcohol consumption categories as the dependent variables in these models. Age (years), smoking status (nonsmokers, 1–20, or ≥21 cigarettes/day), BMI, RDI, and alcohol consumption were used as covariates. In addition, to assess the combined effect of alcohol consumption and SDB on hypertension, the combinations of alcohol consumption (<1.0 and ≥1.0 g/day/kg) and RDI (<10, ≥10, and <10, ≥20 events/h) were recategorized. Multivariable logistic regression analysis was used to examine the association between the combined categories and hypertension. In addition, we investigated whether there was an additive interaction between alcohol consumption and SDB. Relative excess risk due to interaction (RERI) is the excess risk as a result of coexposure [27]. RERI was calculated using the following formula:

RERI = exponent (β1 + β2 + β3) − exponent (β1) − exponent (β2) + 1

(β1, β2, and β3 are the coefficients from the models for estimating odds ratios according to the combination of alcohol consumption and SDB.) A value of zero for RERI would mean there is no interaction, or exactly zero additivity; RERI > 0 would mean there is a positive interaction, or more than zero additivity; and RERI < 0 would mean there is a negative interaction, or less than zero additivity. RERI can range from negative infinity to positive infinity. All probability values for statistical tests were two-tailed, and values of p < 0.05 were regarded as statistically significant. All statistical analyses were performed using SAS version 9.4 software (SAS Institute, Cary, NC).

Results

Table 1 shows the characteristics of the participants according to RDI and alcohol consumption categories. Higher alcohol consumption was significantly associated with older age, higher SBP and DBP, higher RDI, higher proportion of smokers and individuals with hypertension, and lower BMI (p for trend <0.01). Furthermore, the mean values of age, BMI, and alcohol consumption; the median RDI; and the proportion of individuals with hypertension were higher depending on the severity of RDI (p for trend <0.01).

Table 1 Characteristics of study participants (Japanese male bus drivers) by alcohol consumption and respiratory disturbance index (RDI)
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Table 2 shows that age- and multivariable-adjusted ORs (95% CI) of hypertension for the alcohol consumption groups (<0.5, 0.5 to <1.0, and ≥1.0 g/day/kg) were 1.33 (1.09–1.63), 1.79 (1.41–2.27), and 1.89 (1.40–2.55), respectively, compared with nondrinkers (p for trend <0.01). The results remained significant after further adjustment for RDI (p for trend <0.01).

Table 2 Multivariable-adjusted odds ratios and 95% confidence intervals of hypertension by alcohol consumption categories
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Table 3 shows that age- and multivariable-adjusted ORs (95% CI) of hypertension for the RDI categories (10 to <20 events/h and ≥20 events/h) were 1.21 (0.99–1.48) and 1.29 (1.04–1.60), respectively, compared to the group with RDI < 10 events/h (p for trend = 0.03). The results remained marginally significant after further adjustment for alcohol consumption (p for trend = 0.053).

Table 3 Multivariable-adjusted odds ratios and 95% confidence intervals of hypertension, according to categories of respiratory disturbance index (RDI)
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Table 4 shows age- and multivariable-adjusted ORs (95% CI) of hypertension according to the combination of alcohol consumption and RDI. The multivariable-adjusted ORs (95% CI) of hypertension for the group with alcohol consumption <1.0 g/day/kg and RDI ≥ 10 events/h, alcohol consumption ≥1.0 g/day/kg, and RDI < 10 events/h, and alcohol consumption ≥1.0 g/day/kg and RDI ≥ 10 events/h were 1.18 (0.98–1.43), 1.12 (0.65–1.92), and 1.89 (1.34–2.65), respectively, compared to those with alcohol consumption <1.0 g/day/kg and RDI < 10 events/h. Similarly, the multivariable-adjusted ORs (95% CI) of hypertension for the group with alcohol consumption <1.0 g/day/kg and RDI ≥ 20 events/h, alcohol consumption ≥1.0 g/day/kg and RDI < 10 events/h and alcohol consumption ≥1.0 g/day/kg and RDI ≥ 20 events/h were 1.19 (0.95–1.50), 1.12 (0.65–1.93), and 2.41 (1.45–4.00), respectively, compared to those with alcohol consumption <1.0 g/day/kg and RDI < 10 events/h. The RERI values for the combination of alcohol consumption of ≥1.0 g/day/kg with RDI ≥ 10 events/h or RDI ≥ 20 events/h were 0.59 (−0.25–1.42) and 1.10 (−0.22–2.42), respectively. This indicates that the combination of alcohol consumption and SDB did not have a significant supra-additive effect on hypertension.

Table 4 Multivariable-adjusted odds ratios and 95% confidence intervals for hypertension according to the combinations of alcohol consumption and respiratory disturbance index (RDI) categories
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Discussion

Our study showed that the severity of SDB and alcohol consumption were independently associated with hypertension among Japanese male bus drivers. The results of our study were consistent with those of previous epidemiological studies [4, 17,18,19,20,21,22,23,24]. We also analyzed the combined effect of alcohol consumption and SDB on hypertension. The results showed that participants with high RDI who were alcohol drinkers had higher ORs than those with either factor alone, even after adjustment for potential confounding factors. These results suggest that the combination of alcohol consumption and SDB seems to be more harmful to arterial blood pressure than either factor alone. To the best of our knowledge, this is the first study to show the combined effect of alcohol consumption and SDB on hypertension in a large population of bus drivers.

In this study, the RERI values for the combination of alcohol consumption of ≥1.0 g/day/kg with RDI ≥ 10 events/h or RDI ≥ 20 events/h were 0.59 (−0.25–1.42) and 1.10 (−0.22–2.42), respectively, suggesting that there may be a supra-additive effect. However, we could not find a significant supra-additive effect of the combination of alcohol consumption and SDB on hypertension. This suggests that alcohol consumption and SDB are independently associated with hypertension via different pathways.

Our study population included higher proportions of individuals who were overweight (43%) and alcohol drinkers (62%) and who had a higher RDI (16.0 events/h) (not shown in tables) than the Japanese male general population (overweight: 31%, alcohol drinkers: 33%, RDI: 8.3 events/h) [28, 29]. These unhealthy characteristics are consistent with previous studies from the United States, which reported that 89% of professional drivers were overweight [30]. Obesity and alcohol intake are known important risk factors for SDB [10, 31], and these factors are independently associated with hypertension [17,18,19,20,21,22,23,24]. Thus, bus drivers may be at a higher risk of hypertension, and the combination of these risk factors may impose a higher risk of hypertension than each factor alone. These results emphasize the need for comprehensive approaches and measures, such as the Swiss cheese model, which is a model for mitigating the risk with different types of defense layers, to control hypertension among bus drivers [32].

What are the mechanisms mediating the biological effects of alcohol consumption and SDB on hypertension? While our study did not directly examine this issue, the potential mechanisms include baroreceptor impairment, destabilization of the central nervous system, and stimulation of the renin–angiotensin system [16]. On the other hand, the hypoxemia resulting from SDB associated with upper airway narrowing/obstruction possibly links SDB to hypertension [31, 33]. Hypoxemia results in increased sympathetic nerve activity and vasoconstriction, leading to hypertension [34]. Therefore, the risk of hypertension might be further increased in individuals with these two overlapping mechanisms.

The strength of this study was the analysis of the combined effect of alcohol consumption and SDB on hypertension in a large population of 2525 bus drivers after adjustment for potential confounding factors, allowing the results to be statistically robust. However, we acknowledge several limitations related to the study design. First, since the study was cross-sectional, no causal relationship could be confirmed. Second, a self-administered questionnaire was used to determine SBP and DBP in this study. Although the data were collected by a self-administered questionnaire, the validity of the self-report method in the assessment of these variables has already been confirmed with a high correlation (r = 0.73 for SBP, r = 0.67 for DBP) [35, 36]. Third, SDB was defined by RDI using a nasal flow sensor rather than by AHI based on overnight PSG. However, we have previously demonstrated a high correlation between RDI recorded by this technology and AHI assessed by polysomnography [26]. Fourth, although we examined the association of alcohol consumption and SDB with hypertension after adjustment for age, BMI, and smoking status, there are other potential confounding factors, e.g., work patterns, psychological stress, and diabetes. In this study, we could not control for these potential confounding factors because these data were not available in this study. Further studies are needed to consider these issues. Fifth, despite the large study population of 2525 bus drivers, they were recruited on a voluntary basis in this study. Therefore, we cannot guarantee the representativeness of our study population and need to be cautious in generalizing our findings to other populations.

Conclusions

The present study examined the combined effect of alcohol consumption and SDB on hypertension in Japanese male bus drivers, and the results demonstrated that the combination of alcohol consumption and SDB seems to be more harmful to arterial blood pressure than either factor alone. The simultaneous approach of both screening for SDB and health education on excessive alcohol consumption may be important in the management of hypertension among Japanese male bus drivers.