Anders Knutsson

Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27 485 people

OBJECTIVES To explore how metabolic risk factors for cardiovascular disease (CVD) differ between shift workers and day workers in a defined population. Shift work has been associated with an increased risk of CVD. Risk factors and causal pathways for this association are only partly known. METHODS A working population of 27 485 people from the Västerbotten intervention program (VIP) has been analysed. Cross sectional data, including blood sampling and questionnaires were collected in a health survey. RESULTS Obesity was more prevalent among shift workers in all age strata of women, but only in two out of four age groups in men. Increased triglycerides (>1.7 mmol/l) were more common among two age groups of shift working women but not among men. Low concentrations of high density lipoprotein (HDL) cholesterol (men<0.9 and women<1.0 mmol/l) were present in the youngest age group of shift workers in both men and women. Impaired glucose tolerance was more often found among 60 year old women shift workers. Obesity and high triglycerides persisted as risk factors in shift working men and women after adjusting for age and socioeconomic factors, with an OR of 1.4 for obesity and 1.1 for high triglyceride concentrations. The relative risks for women working shifts versus days with one, two, and three metabolic variables were 1.06, 1.20, and 1.71, respectively. The corresponding relative risks for men were 0.99, 1.30, and 1.63, respectively. CONCLUSIONS In this study, obesity, high triglycerides, and low concentrations of HDL cholesterol seem to cluster together more often in shift workers than in day workers, which might indicate an association between shift work and the metabolic syndrome.

Shift work, risk factors and cardiovascular disease

The literature on shift work, morbidity and mortality from cardiovascular disease, and changes in traditional risk factors is reviewed. Seventeen studies have dealt with shift work and cardiovascular disease risk. On balance, shift workers were found to have a 40% increase in risk. Causal mechanisms of this risk via known cardiovascular risk factors, in relation to circadian rhythms, disturbed sociotemporal patterns, social support, stress, behavior (smoking, diet, alcohol, exercise), and biochemical changes (cholesterol, triglycerides, etc) are discussed. The risk is probably multifactorial, but the literature has focused on the behavior of shift workers and has neglected other possible causal connections. In most studies methodological problems are present; these problems are related to selection bias, exposure classification, outcome classification, and the appropriateness of comparison groups. Suggestions for the direction of future research on this topic are proposed.

Job strain as a risk factor for coronary heart disease: A collaborative meta-analysis of individual participant data

Summary Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985–2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10–1·37). This effect estimate was higher in published (1·43, 1·15–1·77) than unpublished (1·16, 1·02–1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15–1·48) and 5 years (1·30, 1·13–1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

INCREASED RISK OF ISCHAEMIC HEART DISEASE IN SHIFT WORKERS

504 papermill workers were followed up for 15 years and the incidence of ischaemic heart disease (IHD) in shift workers was compared with that in day workers. The relative risk (RR) of IHD rose with increasing duration of reported exposure to shift work. A significant risk of IHD was associated with an exposure of 11 - 15 years (RR = 2.2, p less than 0.04) and of 16 to 20 years (RR = 2.8, p less than 0.03. The association was independent of age and smoking history. The RR of IHD fell sharply after 20 years of shift work. This was ascribed to the pronounced positive selection that had taken place in this group.

Atopic sensitization and respiratory symptoms among Polish and Swedish school children

Allergic sensitization and symptoms from the airways in relation to air pollution were compared in 10–12‐year‐old school children (n= 1113) from urban Konin in central Poland and both urban and rural parts of Sundsvall in northern Sweden. The measurements included parental questionnaires, skin‐prick tests and serial peak flow measurements during 2 weeks with simultaneous monitoring of outdoor air pollutants. The skin‐prick test technique was validated by IgE antibody determinations. The levels of common industrial pollutants, SO2 and smoke particles were much higher in Konin than in urban Sundsvall and the levels of NO2 were similar. Various respiratory symptoms were more often reported among school children in Konin (except for wheezing and diagnosed asthma). Multiple logistic regression analyses yielded the following increased odds ratios for children in Konin as compared with the reference group (rural Sundsvall): chest tightness and breathlessness 348 (95% confidence interval 2.08–5.82), exercise‐induced coughing attacks 3.69 (95% confidence interval 1.68–8.10), recurrent episodes of common cold 2.79 (95% confidence interval 1.53–5.09) and prolonged cough 4–89 (95% confidence interval 2.59–9.23). In contrast, as compared with rural Sundsvall, the adjusted odds ratio for a positive skin‐prick test was decreased in Konin, but increased in urban Sundsvall, 0.58 (95% confidence interval 0.37–0.91) and 1.67 (95% confidence interval 1.15–2.42) respectively. The study confirms that living in urban, as compared with rural areas, is associated with an increased prevalence of respiratory symptoms and sensitization to allergens. These differences could be explained by air pollution. Respiratory symptoms were more common in a similar urban group of Polish children who were exposed to even higher levels of air pollution. These children, however, had a much lower prevalence of sensitization to allergens, as compared with the Swedish children. This indicates that differences in lifestyle and standard of living between western Europe and a former socialist country influences the prevalence of atopy.

Shiftwork and cardiovascular disease: review of disease mechanisms.

This paper reviews the main findings concerning mechanisms explaining the increased risk of coronary heart disease (CHD) in shiftworkers. We discuss a conceptual model, in which three main shiftwork pathways to CHD are postulated--social problems, behavioral change, and disturbed circadian rhythm. Social problems that are associated with shiftwork might lead to stress. Significant shiftwork-related behavioral problems are smoking and unhealthy food habits. Disturbed circadian rhythm might result in sleep deprivation. Unphysiologic timing of physical activity and food intake in relation to circadian rhythms is another possible explanation for the negative impact on the cardiovascular system.

Shiftwork and myocardial infarction: a case-control study

OBJECTIVES: Previous studies have indicated an association between shiftwork and coronary heart disease. The increased risk could be due to job strain, which could act as a mediator of disease. There is also a possibility that interaction between shiftwork and job strain could occur that may induce or modify the development of disease. We conducted this study to explore the relation between shiftwork, job strain, and myocardial infarction. METHODS: 2006 cases with acute first time myocardial infarction were compared with 2642 controls without symptoms of myocardial infarction, and obtained from the same population that gave rise to the cases (population based case-control study). RESULTS: Myocardial infarction risk was associated with shiftwork both in men (odds ratio (OR) 1.3, 95% confidence interval (95% CI) 1.1 to 1.6) and women (OR 1.3, 95% CI 0.9 to 1.8). In the age group 45-55, the relative risk was 1.6 in men and 3.0 in women. The results cannot be explained by job strain, age, job education level, or smoking. No interaction was found between shiftwork and job strain. CONCLUSIONS: The findings indicate that shiftwork is associated with myocardial infarction in both men and women. The mechanism is unclear, but the relation cannot be explained by job strain, smoking, or job education level.

Risk factors for respiratory symptoms and atopic sensitisation in the Baltic area.

Recent studies have indicated that atopic sensitisation is uncommon while respiratory symptoms are common among schoolchildren in Eastern Europe. Risk factors for respiratory symptoms and atopic sensitisation were evaluated in a cross sectional study involving 2594 schoolchildren (10-12 years) from Sweden (n = 665), Poland (n = 410), and Estonia (n = 1519). The measurements included parental questionnaires and skin prick tests with eight standardised allergens. Multiple logistic analyses demonstrated that atopic heredity was a significant independent risk factor for respiratory symptoms and atopic sensitisation in all the countries. Current dampness and maternal smoking were related to respiratory symptoms whereas domestic crowding, male gender, and passive smoking during infancy were related to atopic sensitisation. Current maternal smoking had a strong dose response association with current coughing attacks (nocturnal cough > 4 weeks or exercise induced coughing attacks) but only in Eastern Europe. A strong inverse relationship was recorded between domestic crowding and sensitisation as the risk for sensitisation increased with decreasing number of persons per room in the household (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.43 to 0.77). Exposure to tobacco smoke at home during infancy was a risk factor for atopic sensitisation but only to animal dander and only in Eastern Europe (OR 1.41, 95% CI 1.03 to 1.93). In conclusion, there were small differences in the pattern of risk factors between Eastern and Western Europe. The only exception was environmental tobacco smoke being a risk factor only in Eastern Europe. The study also suggests that factors related to domestic crowding protect against atopic sensitisation in Estonia and Poland. A higher standard of living with less crowding may give rise to an increasing prevalence of atopic sensitisation also in Eastern Europe.

Long working hours and risk of coronary heart disease and stroke : a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

BACKGROUND Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. METHODS We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. FINDINGS We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603,838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528,908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5·1 million person-years (mean 8·5 years), in which 4768 events were recorded, and for stroke was 3·8 million person-years (mean 7·2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (≥55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1·13, 95% CI 1·02-1·26; p=0·02) and incident stroke (1·33, 1·11-1·61; p=0·002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1·30-1·42). We recorded a dose-response association for stroke, with RR estimates of 1·10 (95% CI 0·94-1·28; p=0·24) for 41-48 working hours, 1·27 (1·03-1·56; p=0·03) for 49-54 working hours, and 1·33 (1·11-1·61; p=0·002) for 55 working hours or more per week compared with standard working hours (ptrend<0·0001). INTERPRETATION Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours. FUNDING Medical Research Council, Economic and Social Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), US National Institutes of Health, British Heart Foundation.

Work stress and risk of cancer : meta-analysis of 5700 incident cancer events in 116 000 European men and women

Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers. Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116 056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intake Results A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer. Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.