Chronic stress at work and the metabolic syndrome: prospective study

Variables

Data on the components of the metabolic syndrome were collected at phase 5 (1997-9) during the clinical examination, using the definition of the National Cholesterol Education Program (adult treatment panel III) (table 1).7 The syndrome was defined by the presence of three or more risk factors. Components of the metabolic syndrome were not measured at baseline. We used obesity (defined as body mass index > 30) at baseline as an indicator of risk for the syndrome.

We measured self reported work stress using the job strain questionnaire.15 Work stress was present when participants' responses to questions about the job demands were high and those to questions about decision latitude (job control) were low (defined as above or below the median score for the measures of “job demands” and “job decision latitude”). The iso-strain model is one of several variants of this concept of work stress; this model hypothesises that socially isolated (that is, no supportive coworkers or supervisors) high job strain carries the highest risk for heart disease. Iso-strain is a parsimonious instrument for measuring and analysing workplace conditions.16 We defined participants in the lowest third of work social support who reported job strain (high job demands and low job control) as having work stress17 and measured the accumulation of exposure to work stress over the four measurement periods (phases 1, 2, 3 and 5) by adding together the number of times the participant was exposed to iso-strain. We defined chronic work stress as experiencing iso-strain three or more times (> 75% of the time) over the 14 year study period. Participants who lacked work stress data at any of the phases of data collection were given a missing value.

We measured social position using the relative index of inequality, based on employment grade at baseline. Values of 0 and 1 correspond to subjects who are at the top and bottom of the socioeconomic hierarchy. The health behaviours (all self reported) analysed were: current smoking, no daily fruit and vegetable consumption, heavy alcohol consumption (men > 4 units/day, women > 3 units/day), and no exercise. We summed exposure to these health damaging behaviours over the four measurement periods (phases 1, 2, 3 and 5) and assigned a missing value to participants who lacked data on a specific health behaviour at any of the time periods.

Analysis

We used logistic regression analysis to assess the odds ratios of the metabolic syndrome for the different explanatory variables and nested logistic regression models to examine the effect of adjusting for different explanatory variables. We excluded 70 patients with heart disease (non-fatal myocardial infarction) at baseline from all the analyses and in some analyses also excluded the 717 obese (body mass index > 30) patients at baseline, to test the causal direction from work stress to the metabolic syndrome and associated obesity.

Missing data and cohort dropout

The first phase of the Whitehall II study (1985-8) comprised 10 308 civil servants. By phase 5 of the study (1997), the participation rate was 75%, taking into account 488 deaths among the 7357 participants at this stage; 5882 had complete clinical data on the indicators of the metabolic syndrome.

Our missing data analysis procedures used missing at random (MAR) assumptions. We used the MICE (multivariate imputation by chained equations) method of multiple multivariate imputation in STATA.18 19 We independently analysed 10 copies of the data, each with missing values suitably imputed, in the multivariate logistic regression analyses. We averaged estimates of the variables to give a single mean estimate and adjusted standard errors according to Rubin's rules.20

A missing value on the work stress measure could indicate that the data were not available at a particular phase, the participant dropped out, or the participant was not in employment. In the last situation, the imputed values for the work stress variables include non-applicable values for respondents who had retired from work by phase 5. Hence, we analysed only those respondents who had not retired by phase 5 (imputed n = 7034 out of 10 238) in the multivariate models using the imputed data. Participants who were in employment and had never experienced work stress during the 14 years formed the reference group for the work stress measure for both the complete cases and imputed analyses.

Main findings

Greater exposure to job stress over 14 years was linked to greater risk of the metabolic syndrome, in a dose-response manner. The association was robust to adjustment for occupational status and health behaviours. These prospective findings are evidence of the biological plausibility of a causal association between chronic psychosocial stress and the risk of chronic heart disease. Crucially, by excluding participants who were obese at baseline, we showed that pre-existing physiological risk is unlikely to explain the observed association. Furthermore, the social gradient in the metabolic syndrome is partially explained by work stress and a larger proportion is explained by health behaviours.

By characterising work stress exposure with multiple measures, we have conducted an innovative and rigorous study of the cumulative effect of psychosocial adversity on the clustering of coronary risk factors. It is unclear whether the development of risk seen here is due in part to the direct effects of chronic stress on insulin resistance, resting blood pressure, and lipoprotein metabolism, although this interpretation is supported by Whitehall II and other studies.3 5 21 We took account of smoking habit, physical inactivity, poor diet, and excess alcohol intake with repeated measurements over the course of follow-up. Each of these adverse health behaviours predicted the risk of the metabolic syndrome in men and, less consistently, in women, but there was little evidence that these behaviours mediated or confounded the effect of work stress on the risk of developing the syndrome. The effect of chronic work stress on unhealthy behaviours remains a question for future research.

Biology of stress

Prolonged exposure to work stress may affect the autonomic nervous system and neuroendocrine activity directly, contributing to the development of the metabolic syndrome. A case-control study showed that participants in the Whitehall II study with the metabolic syndrome had raised cortisol and normetanephrine output, and also had reduced variability in heart rate.5 Decrements in cardiac autonomic function have been linked to the metabolic syndrome in other populations and to low job control and social isolation among men in the Whitehall II study.6 22 23 Psychobiological studies have also shown that heightened stress reactivity and impaired recovery after stress, assessed by blood pressure and inflammatory markers, predict the five year progression of the metabolic syndrome.20 Chronic psychological stress may reduce biological resilience and thus disturb homoeostasis. Altered adrenocortical function can influence hepatic lipoprotein metabolism and insulin sensitivity at target organs.21 24 Cortisol is an insulin antagonist, and cortisol output is increased in the metabolic syndrome.5 Low concentrations of high density lipoprotein cholesterol and glucose intolerance have been linked with high basal secretion of cortisol.25

Limitations

We were not able to analyse incidence because of the lack of data on all metabolic syndrome components at study baseline. Over-weight people may be more socially isolated and may find working conditions more stressful. However, excluding obese participants at baseline did not change our findings. Missing data are a common problem in all cohort studies. Although the dropout rate between phases 1 and 5 of this study was high, we used analytical procedures that take account of missing data. The results using imputed data were in line with the results from the analysis of the complete cases. Few women had chronic exposure to work stress, necessitating the analysis of men and women together.

Conclusions

A dose-response association exists between exposure to work stress and the metabolic syndrome. Employees with chronic work stress have more than double the odds of the syndrome than those without work stress, after other risk factors are taken into account. The study provides evidence for the biological plausibility of psychosocial stress mechanisms linking stressors from everyday life with heart disease.