Background
Hyperuricemia (HUA) refers to a group of metabolic disorders. To be more specific, the concentration of uric acid in the blood is too high due to chronic impairment of purine nucleotide metabolism and, or abnormal excretion of uric acid in the body [
1]. In the early stages, hyperuricemia is characterized only by elevated blood uric acid concentration and is highly insidious. Gouty arthritis and, in severe instances, renal impairment can develop when the blood is saturated with urate [
2]. Studies have confirmed that hyperuricemia not only causes gouty arthritis and renal impairment but is also associated with type 2 diabetes, hypertension, coronary artery disease, endothelial dysfunction, and metabolic syndrome [
3‐
7]. A study of 36,348 adults showed that the prevalence of hyperuricemia among Chinese adults was 8.4% in 2009–2010 [
8]. In 2015, a mate-analysis conducted by Liu R et al. involving 44 epidemiological surveys in 16 provinces, municipalities, and autonomous regions in the mainland of China, revealed that the overall prevalence of hyperuricemia in China was 13.3% [
9]. In addition, the prevalence of hyperuricemia among US adults, significantly higher than the results of the 1988–1994 survey (18.2%), rises to 20.1% according to the 2007–2016 US National Health and Nutrition Examination Survey [
10]. Thus, it appears that the prevalence of hyperuricemia is increasing every year.
Studies have shown that heat exposure can lead to kidney damage [
11], which in turn can affect the metabolism of uric acid. Roncal-Jimenez CA et al. carried out an animal experiment in which mice exposed to heat for 5 weeks had higher serum uric acid levels, indicating that heat exposure is associated with elevated uric acid in the serum [
12]. A large case–control study was conducted, and the results revealed a link between inorganic dust exposure and gout [
13]. In addition, a Russian study showed a higher prevalence of hyperuricemia in oil press workers exposed to chronic noise than that in the general population [
14]. Different production processes in steel plants involve a variety of occupational hazards such as heat, noise, dust, and long irregular shifts, all of which can be hazardous to the health of workers in steel companies and give rise to various diseases. LI X et al. conducted a survey of steelworkers and made an analysis. They found that the prevalence of hyperuricemia among steelworkers was 35.9% [
15], which was higher than that of the general population. The factors that affect hyperuricemia have been extensively studied [
16‐
19]. However, these studies have mainly focused on social behavior, dietary habits, and genetic factors. There have been very few investigations into the influence of occupational hazardous variables on hyperuricemia. Hence, the current study was carried out to look into the connection between occupational exposure and the development of hyperuricemia in workers at a steel company. Besides, the interactions between occupational hazards were examined.
Methods
Population study
The participants in this study were workers of a steel company who underwent occupational health screening at Hongci Hospital, Tangshan City, Hebei Province, China, from March 2017 to September 2017. Cohort inclusion criteria: formally employed workers, at least one year of service. Cohort exclusion criteria: hyperuricemia and refusal to participate in this cohort study. A total of 4,247 workers from the steel company were included in the cohort. A follow-up survey of a total of 3,706 steelworkers between March 2019 and September 2019 was carried out, with a 12.74% missing rate. Workers in the cohort with new-onset hyperuricemia in steel companies are regarded as the case group. From this cohort population, each new-onset patient was matched with a worker in the steel company without hyperuricemia as a control according to the principle of matched design (the same sex and age) to form a control group. A total of 641 case and control pairs were eventually included as samples after those with incomplete information were excluded.
All participants have read and signed the informed consent form. The subject was approved by the Medical Ethics Committee of the North China University of Technology (No.15006).
Questionnaire
A one-on-one survey was conducted by uniformly trained enumerators with a questionnaire designed by the subject group. The contents of the questionnaire included sex, age, household size, monthly household income, education level, marital status, smoking status, drinking status, tea status, physical exercise, type of work, change in type of work, shift work, type of shift, change in shift work, change in working hours, daily working hours, monthly rest time, and personal disease history. The participants were also asked about the frequency of food intake (0 day per week, 1–2 days per week, 3–6 days per week, and 7 days per week). Food was divided into different groups: vegetables, fruits, meat, eggs, dairy products, soy products, and seafood.
Physical examination
The participants took off their shoes when their height and weight were measured through the ultrasound height and weight measuring device. Measurements were taken three times and averaged. The body mass index (BMI) was calculated based on the measurement. The participant was instructed not to drink tea, coffee, alcohol or other beverages that may affect the results of blood pressure. The participant was asked to have a five-minute break before the blood pressure measurement and to take the measurement three times with an interval of not less than three minutes.
Laboratory examination
Subjects were required to fast for 12 h. Fasting blood and morning urine were collected by the Laboratory Department of Tangshan Hongci Hospital before 9 a.m. the next day. Blood, urine, and blood biochemistry were examined by specialist physicians.
On-site hygienic investigation
The on-site hygienic survey involved heat, dust, and noise.
The measurement tool for temperature is Wet Bulb Black Globe Temperature Gauge (WBGT). According to relevant standard [
20], the temperature should be measured during the hottest season of the year. Temperatures were measured at different workplaces in consideration of the specific conditions of the steel production unit. Three to six measurement points were selected for each workplace, and the test was repeated three times at each measurement point, with the average taken as the final result.
Dust was measured with a dust sampler. The sampling points were chosen according to relevant standard [
21] and specific conditions of the workshop. The sample collection time for each sampling point was 45 min, and the flow rate of the dust sampler was set at 40 L/min. The calculation formula is as follows:
$$\begin{array}{c}C=\frac{\mathrm{m}2-\mathrm{m}1}{\mathrm{Q}\times \mathrm{t}}\times 1000\#\end{array}$$
(1)
where: C- dust concentration, mg/m.3
m2—the mass of the filter membrane after sampling, mg.
m1—the mass of the filter membrane before sampling, mg.
Q—flow rate, L/min.
t—sampling time, min.
Noise testing was carried out according to relevant standards [
22,
23] and specific circumstances of the workplace. When the noise distribution in the workshop was uneven, the noise was divided into different sound zones according to the sound level and two test points were set up in each zone. When the noise distribution in the workshop was relatively even (the sound level difference is less than or equal to 3 dB (A)), three measurement points were set up. The average value was taken as the final result after measurement. The calculation formula for sound level measurement is as follows:
$${L}_{Aeq,T}=10\text{lg(}\frac{1}{T}{\sum }_{i=1}^{n}{T}_{i}{10}^{0.1{L}_{Aeq,{T}_{i}}})$$
(2)
where: \({L}_{Aeq, {T}_{i}}\)- equivalent sound level during the time period Ti.
\({L}_{Aeq, T}\)—equivalent sound level for a full day.
n—the total number of periods.
T—the duration of each period.
Ti- i period of time.
Cumulative exposure measurement (CEM) for steelworkers is calculated based on the results of the on-site hygienic survey, combined with the change in work status and duration of occupational exposure. The formula is as follows:
$$\mathrm{CEM}={\mathrm{L}}_{1} {\mathrm{T}}_{1}+ {\mathrm{L}}_{2} {\mathrm{T}}_{2}\dots \dots +{\mathrm{L}}_{\mathrm{n}} {\mathrm{T}}_{\mathrm{n}}$$
(3)
where: Ln is the average exposure to the target harmful factor over a period of time Tn.
Definition and grouping of indicators
Those having a blood uric acid value greater than or equal to 7.0 mg/dL in men and 6.0 mg/dL in women, as well as previous or ongoing gout treatment, were diagnosed with hyperuricemia [
24]. Never smokers were defined as those who had never smoked from birth to the time of the survey. Former smokers were defined as those who had previously smoked but had quit smoking for 6 months or longer as of this survey. People who had smoked at least 1 cigarette per day for six months or longer as of the survey were defined as current smokers. People who drank alcohol more than twice a week, regardless of the type of alcohol, and who had done so for more than a year were considered to be drinking. The frequency of food consumption was divided into four categories: never (0 day per week), occasionally (1–2 days per week), frequently (3–6 days per week) and daily (7 days per week). In this study, the International Physical Activity Questionnaire (IPAQ) was used to analyze the physical activities of steelworkers [
25]. Physical activities were classified into light, moderate, and heavy activities based on intensity, frequency, and overall weekly physical activity level. Shift work is a system of irregular working hours in which one or more teams perform tasks continuously for 24 h by working in shifts without stopping [
26]. The cumulative number of days of night work represents the total number of days of night work done by workers in the steel plant as of the date of the survey. According to relevant standard [
20], work with a productive heat source and WBGT ≥ 25 °C was defined as heat-exposed work. Dust exposure was defined based on the type of work, the work environment, and the findings of the site hygiene [
21]. Exposure to noise was defined as workers who were exposed to a noisy environment where the 8 h/d or 40 h/week equivalent A-weighted sound pressure level is ≥ 80 dB, which may be harmful to health and hearing [
27].
Statistical methods
Continuous variables were described by means and standard deviations, and the differences between groups were obtained through Student’s t-test. The categorical variables were expressed through the number of individuals (%), and χ
2 tests were used for comparisons between groups. Multifactorial analyses were performed and multiplicative interactions between occupational hazard factors were explored with the help of conditional logistic regression models. Additive interactions were assessed using the attributable proportion of interaction (AP), the relative excess risk of interaction (RERI), and the synergy index (SI), calculated using the Excel spreadsheet by Andersson et al. [
28]. The AP is the proportion of the risk due to the interaction in the doubly exposed group. When RERI is positive, it indicates increased risk due to the additive interaction. SI can be interpreted as the ratio of an increased risk due to both exposures to the sum of individual increased risks.
All statistical analyses were performed by dint of IBM SPSS 24.0 and Excel 2019. P < 0.05 was regarded as significant for two-sided tests.
Discussion
With rapid socio-economic development and changes in people’s lifestyles, hyperuricemia has become the second most prevalent metabolic disease after diabetes, seriously affecting people’s quality of life [
29]. Hyperuricemia is a risk factor for many diseases. The deposition of urate crystals can give rise to metabolic disorders and damage to kidney and heart [
30,
31]. Studies have shown that the prevalence of hyperuricemia in adults is increasing year by year. There is a trend of a younger onset of the disease [
9].
In this study, the incidence rate of hyperuricemia in the workers of the steel company investigated was 17.30%. A meta-analysis revealed that 13.3% of people in the mainland of China had hyperuricemia [
9]. The incidence rate of hyperuricemia among workers in steel companies is higher than the average in the mainland of China. It is therefore essential to study the effects of occupational exposure on hyperuricemia in steelworkers.
According to the US 2010 National Health Interview Survey, about one-fifth of the workforce carries out shift work of varying intensities worldwide [
32]. Shift work has many adverse effects on the physical and mental health of workers. Therefore, shift work is one of the occupational hazards that cannot be overlooked. Despite production reforms, shift work is still practiced in the steel industry. Of the 641 sample pairs in this study, 87.7% of workers in the steel enterprise had a history of shift work, and 65.4% of workers in the steel enterprise were currently working in shifts. In this study, after the adjustment of possible confounders, it was found that the ORs (95% CI) for the risk of developing hyperuricemia due to ever shifts and current shifts were 2.18 and 1.81 times higher than that due to never shifts, respectively. The risk of hyperuricemia was increased in both the 0–1,972.80 and ≥ 1,972.80 (days) groups compared to the 0 (day) cumulative days of night work. The ORs were 1.87 and 2.02, respectively, indicating that the risk of developing hyperuricemia rose with the number of cumulative days of night work. A Japanese cohort study revealed that shift work is independently related to elevated serum uric acid in males [
33]. In another study, the risk of hyperuricemia development was 1.41 times higher in steelworkers who worked shifts compared to that of those who didn’t [
34]. The present study echoes with these results. Long-term shift work disrupts physiological functions and the body’s circadian rhythm. At the same time, the biological clock is disturbed, thus impairing uric acid metabolism. Studies suggest that the culprit could be oxidative stress caused by disrupted circadian rhythms [
35].
Heat is among the main occupational hazards for workers in steel companies, and high workplace temperatures can place a burden of disease on occupational groups [
36,
37]. Over 50% of the 641 sample pairs in this study were exposed to heat. The current study showed that heat exposure raised the risk of hyperuricemia development with an OR of 1.58. The risk of developing hyperuricemia was increased in both groups with the cumulative exposure to heat of 0–567.83 and ≥ 567.83 (°C/year) compared to the reference group, respectively. The ORs were 1.50 and 1.64, respectively. Lin QY et al. examined the factors impacting the prevalence of chronic diseases among heat-exposed workers in a port terminal, and the results revealed that the longer the length of labor exposed to heat, the higher the risk of hyperuricemia is (
P < 0.01), which is similar to the results of this study [
38]. The mechanisms involved are hypothesized: firstly, under the hot working conditions, most of the water in the body is excreted in sweat, thus the urinary excretion is significantly reduced and uric acid accumulates. Secondly, the concentration of lactic acid in workers’ bodies rises under high-temperature working conditions. Lactic acid competitively inhibits the excretion of uric acid. The competitive inhibition affects uric acid excretion and the concentration of uric acid increases in the blood. Furthermore, research has demonstrated that exposure to heat might lead to kidney damage [
11]. Kidney damage can affect the normal excretion of uric acid, leading to the accumulation of uric acid and, ultimately, hyperuricemia.
Dust is generated in all links of the steel production process, and exposure to dust is one of the major occupational hazards for steelworkers. This study showed that dust exposure elevated the risk of developing hyperuricemia in comparison to no exposure to dust with an OR of 1.34. The risk of hyperuricemia development was increased in the group with cumulative dust exposure ≥ 30.02 (mg/m
3/year) compared to the reference group. The OR (95%
CI) was 1.56 (1.05–2.32). When dust is inhaled by the body, it not only accumulates in the lungs, but also enters the circulation through the blood barrier and damages other organs [
39]. This has been confirmed by many animal tests [
40,
41]. It is, therefore, speculated that the increased risk of hyperuricemia development from dust exposure may be owing to kidney damage, which affects the normal metabolism of purines and the normal excretion of uric acid, leading to an elevation in uric acid levels in the blood. There are fewer studies on the association between dust and hyperuricemia, and more research is needed to make clarify the exact mechanisms.
The present study showed no statistically significant association between noise exposure and hyperuricemia, which is consistent with the findings of the Zhang SK study [
42]. However, it has also been noted that hyperuricemia is associated with noise exposure in the work environment [
43]. Noise-induced psychological stress may affect purine metabolism and uric acid excretion through neuroendocrine regulation [
44]. Therefore, the effect of noise exposure on hyperuricemia requires additional investigation.
Few research has clarified the interplay of occupational hazards in prior studies on factors affecting hyperuricemia. In this study, the interaction analysis revealed a multiplicative interaction between heat exposure and dust exposure in the development of hyperuricemia. Exposure to both heat and dust significantly increased the risk of hyperuricemia development, which proves the combined effect of some occupational hazards on physical health. This indicates that reducing workers’ heat exposure can lower the risk of hyperuricemia in steelworkers exposed to dust so as to protect their health.
The main strengths of our study lie in a precise calculation of cumulative exposure to occupational hazards and a comprehensive range of potential confounders, which enables a more accurate study on the effect of occupational exposures on hyperuricemia. However, there are some limitations in our study. There was a 12.74% missed visit rate throughout the study, which may have been subject to missed visit bias. High-temperature and dusty weathers may affect the results of this study, but they weren’t taken into account in this study. Moreover, this study is only based on a sample of workers from a steel company in one region. Due to the uniqueness of the occupational environment, the sample size of female workers was small and the representation of the study population was limited. Therefore, a multi-regional and large sample of the target population is required for validation.
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