Eric Brunner

Health inequalities among British civil servants: the Whitehall II study

The Whitehall study of British civil servants begun in 1967, showed a steep inverse association between social class, as assessed by grade of employment, and mortality from a wide range of diseases. Between 1985 and 1988 we investigated the degree and causes of the social gradient in morbidity in a new cohort of 10,314 civil servants (6900 men, 3414 women) aged 35-55 (the Whitehall II study). Participants were asked to answer a self-administered questionnaire and attend a screening examination. In the 20 years separating the two studies there has been no diminution in social class difference in morbidity: we found an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis. Self-perceived health status and symptoms were worse in subjects in lower status jobs. There were clear employment-grade differences in health-risk behaviours including smoking, diet, and exercise, in economic circumstances, in possible effects of early-life environment as reflected by height, in social circumstances at work (eg, monotonous work characterised by low control and low satisfaction), and in social supports. Healthy behaviours should be encouraged across the whole of society; more attention should be paid to the social environments, job design, and the consequences of income inequality.

Contribution of job control and other risk factors to social variations in coronary heart disease incidence

BACKGROUND The first Whitehall Study showed an inverse social gradient in mortality from coronary heart disease (CHD) among British civil servants--namely, that there were higher rates in men of lower employment grade. About a quarter of this gradient could be attributed to coronary risk factors. We analysed 5-year CHD incidence rates from the Whitehall II study to assess the contribution to the social gradient of psychosocial work environment, social support, coronary risk factors, and physical height. METHODS Data were collected in the first three phases of examination of men and women in the Whitehall II study. 7372 people were contacted on all three occasions. Mean length of follow-up was 5.3 years. Characteristics from the baseline, phase 1, questionnaire, and examination were related to newly reported CHD in people without CHD at baseline. Three self-reported CHD outcomes were examined: angina and chest pain from the Rose questionnaire, and doctor-diagnosed ischaemia. The contribution of different factors to the socioeconomic differences in incident CHD was assessed by adjustment of odds ratios. FINDINGS Compared with men in the highest grade (administrators), men in the lowest grade (clerical and office-support staff) had an age-adjusted odds ratio of developing any new CHD of 1.50. The largest difference was for doctor-diagnosed ischaemia (odds ratio for the lowest compared with the highest grade 2.27). For women, the odds ratio in the lowest grade was 1.47 for any CHD. Of factors examined, the largest contribution to the socioeconomic gradient in CHD frequency was from low control at work. Height and standard coronary risk factors made smaller contributions. Adjustment for all these factors reduced the odds ratios for newly reported CHD in the lowest grade from 1.5 to 0.95 in men, and from 1.47 to 1.07 in women. INTERPRETATION Much of the inverse social gradient in CHD incidence can be attributed to differences in psychosocial work environment. Additional contributions were made by coronary risk factors--mainly smoking--and from factors that act early in life, as represented by physical height.

Low job control and risk of coronary heart disease in Whitehall II (prospective cohort) study

Abstract Objective: To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants. Design: Prospective cohort study (Whitehall II study). At the baseline examination (1985-8) and twice during follow up a self report questionnaire provided information on psychosocial factors of the work environment and coronary heart disease. Independent assessments of the work environment were obtained from personnel managers at baseline. Mean length of follow up was 5.3 years. Setting: London based office staff in 20 civil service departments. Subjects: 10 308 civil servants aged 35-55 were examined-6895 men (67%) and 3413 women (33%). Main outcome measures: New cases of angina (Rose questionnaire), severe pain across the chest, diagnosed ischaemic heart disease, and any coronary event. Results: Men and women with low job control, either self reported or independently assessed, had a higher risk of newly reported coronary heart disease during follow up. Job control assessed on two occasions three years apart, although intercorrelated, had cumulative effects on newly reported disease. Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 (95% confidence interval 1.34 to 2.77) compared with subjects with high job control at both occasions. This association could not be explained by employment grade, negative affectivity, or classic coronary risk factors. Job demands and social support at work were not related to the risk of coronary heart disease. Conclusions: Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices. The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease. Key messages Low job control in the work environment contributes to the development of coronary heart disease among British male and female civil servants The risk of heart disease is associated with both objective low job control and perceived low job control. Increase in job control over time decreases the risk of coronary heart disease. This suggests that policies giving people a stronger say in decisions about their work or providing them with more variety in work tasks may contribute to better cardiovascular health

Chronic stress at work and the metabolic syndrome: prospective study

Abstract Objectives To investigate the association between stress at work and the metabolic syndrome. Table 4 Risk of having the metabolic syndrome by relative index of inequality of employment grade. Multivariate multiple imputation logistic regression models: non-retired men and women in the Whitehall II cohort at phase 5 Odds ratio (95% CI) P for linear trend Reduction in log odds from model I Age+sex (model I) 2.33 (1.38 to 3.93) <0.01 Age+sex+work stress 2.13 (1.22 to 3.71) 0.01 10.5% Age+sex+health behaviours 2.04 (1.05 to 3.95) 0.04 15.6% Age+sex+work stress+behaviours 1.86 (0.96 to 3.61) 0.07 26.4% Design Prospective cohort study investigating the association between work stress and the metabolic syndrome. Participants 10 308 men and women, aged 35-55, employed in 20 London civil service departments at baseline (the Whitehall II study); follow-up was an average of 14 years. Main outcome measures Work stress based on the iso-strain model, measured on four occasions (1985-99). Biological measures of the metabolic syndrome, based on the National Cholesterol Education Program definition, measured in 1997-9. Results A dose-response relation was found between exposure to work stressors over 14 years and risk of the metabolic syndrome, independent of other relevant risk factors. Employees with chronic work stress (three or more exposures) were more than twice as likely to have the syndrome than those without work stress (odds ratio adjusted for age and employment grade 2.25, 95% confidence interval 1.31 to 3.85). Conclusions Stress at work is an important risk factor for the metabolic syndrome. The study provides evidence for the biological plausibility of the link between psychosocial stressors from everyday life and heart disease.

Association of Socioeconomic Position With Health Behaviors and Mortality

CONTEXT Previous studies may have underestimated the contribution of health behaviors to social inequalities in mortality because health behaviors were assessed only at the baseline of the study. OBJECTIVE To examine the role of health behaviors in the association between socioeconomic position and mortality and compare whether their contribution differs when assessed at only 1 point in time with that assessed longitudinally through the follow-up period. DESIGN, SETTING, AND PARTICIPANTS Established in 1985, the British Whitehall II longitudinal cohort study includes 10 308 civil servants, aged 35 to 55 years, living in London, England. Analyses are based on 9590 men and women followed up for mortality until April 30, 2009. Socioeconomic position was derived from civil service employment grade (high, intermediate, and low) at baseline. Smoking, alcohol consumption, diet, and physical activity were assessed 4 times during the follow-up period. MAIN OUTCOME MEASURES All-cause and cause-specific mortality. RESULTS A total of 654 participants died during the follow-up period. In the analyses adjusted for sex and year of birth, those with the lowest socioeconomic position had 1.60 times higher risk of death from all causes than those with the highest socioeconomic position (a rate difference of 1.94/1000 person-years). This association was attenuated by 42% (95% confidence interval [CI], 21%-94%) when health behaviors assessed at baseline were entered into the model and by 72% (95% CI, 42%-154%) when they were entered as time-dependent covariates. The corresponding attenuations were 29% (95% CI, 11%-54%) and 45% (95% CI, 24%-79%) for cardiovascular mortality and 61% (95% CI, 16%-425%) and 94% (95% CI, 35%-595%) for noncancer and noncardiovascular mortality. The difference between the baseline only and repeated assessments of health behaviors was mostly due to an increased explanatory power of diet (from 7% to 17% for all-cause mortality, respectively), physical activity (from 5% to 21% for all-cause mortality), and alcohol consumption (from 3% to 12% for all-cause mortality). The role of smoking, the strongest mediator in these analyses, did not change when using baseline or repeat assessments (from 32% to 35% for all-cause mortality). CONCLUSION In a civil service population in London, England, there was an association between socioeconomic position and mortality that was substantially accounted for by adjustment for health behaviors, particularly when the behaviors were assessed repeatedly.

Adrenocortical, Autonomic, and Inflammatory Causes of the Metabolic Syndrome Nested Case-Control Study

Background—The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. Methods and Results—This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both −0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r =−0.19;P =0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. Conclusions—Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.

Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study

BACKGROUND Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes. We aimed to characterise trajectories of fasting and postload glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes. METHODS We analysed data from our prospective occupational cohort study (Whitehall II study) of 6538 (71% male and 91% white) British civil servants without diabetes mellitus at baseline. During a median follow-up period of 9.7 years, 505 diabetes cases were diagnosed (49.1% on the basis of oral glucose tolerance test). We assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). FINDINGS Multilevel models adjusted for age, sex, and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics (10,989 measurements), except for insulin secretion that did not change during follow-up. In the diabetic group (801 measurements), a linear increase in fasting glucose was followed by a steep quadratic increase (from 5.79 mmol/L to 7.40 mmol/L) starting 3 years before diagnosis of diabetes. 2-h postload glucose showed a rapid increase starting 3 years before diagnosis (from 7.60 mmol/L to 11.90 mmol/L), and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis (to 86.7%). HOMA beta-cell function increased between years 4 and 3 before diagnosis (from 85.0% to 92.6%) and then decreased until diagnosis (to 62.4%). INTERPRETATION In this study, we show changes in glucose concentrations, insulin sensitivity, and insulin secretion as much as 3-6 years before diagnosis of diabetes. The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups. FUNDING Medical Research Council (UK); Economic and Social Research Council (UK); British Heart Foundation (UK); Health and Safety Executive (UK); Department of Health (UK); National Institute of Health (USA); Agency for Health Care Policy Research (USA); the John D and Catherine T MacArthur Foundation (USA); and Academy of Finland (Finland).

Work stress and coronary heart disease: what are the mechanisms?

AIMS To determine the biological and behavioural factors linking work stress with coronary heart disease (CHD). METHODS AND RESULTS A total of 10 308 London-based male and female civil servants aged 35-55 at phase 1 (1985-88) of the Whitehall II study were studied. Exposures included work stress (assessed at phases 1 and 2), and outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7), and incident CHD (phases 2-7) on the basis of CHD death, non-fatal myocardial infarction, or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17-2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome. CONCLUSION Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.

Social inequality in coronary risk: central obesity and the metabolic syndrome. Evidence from the Whitehall ii study

SummaryThis report describes the social distribution of central obesity and the metabolic syndrome at the Whitehall II study phase 3 examination, and assesses the contribution of health related behaviours to their distribution. Cross-sectional analyses were conducted utilising data collected in 1991–1993 from 4978 men and 2035 women aged 39–63 years who completed an oral glucose tolerance test. There was an inverse social gradient in prevalence of the metabolic syndrome. The odds ratio (95 % confidence interval) for having the metabolic syndrome comparing lowest with highest employment grade was: men 2.2 (1.6–2.9), women 2.8 (1.6–4.8). Odds ratios for occupying the top quintile of the following variables, comparing lowest with highest grade, were, for waist-hip ratio: men 2.2 (1.8-2.8), women 1.6 (1.1-2.4); post-load glucose: men 1.4 (1.1-1.8), women 1.8 (1.2-2.6); triglycerides: men 1.6 (1.2-2.0), women 2.2 (1.5-3.3); fibrinogen: men 1.7 (1.4-2.3), women 1.9 (1.2-2.8). Current smoking status, alcohol consumption and exercise level made a small contribution (men 11%, women 9%) to the inverse association between socioeconomic status and metabolic syndrome prevalence. In conclusion, central obesity, components of the metabolic syndrome and plasma fibrinogen are strongly and inversely associated with socioeconomic status. Our findings suggest the metabolic syndrome may contribute to the biological explanation of social inequalities in coronary risk. Health related behaviours appear to account for little of the social patterning of metabolic syndrome prevalence.

STRESS AND THE BIOLOGY OF INEQUALITY

Abstract It is well established that health depends on socioeconomic circumstances, but the biology of this relation is not well described. Psychosocial factors operating throughout the life course, beginning in early life, influence a variety of biological variables. Research with non-human primates shows the effects of dominance hierarchy on biology, and similar metabolic differentials are evident in a hierarchy of white collar civil servants. The neuroendocrine “fight or flight” response produces physiological and metabolic alterations which parallel those observed with lower socioeconomic status. The biological effects of the psychosocial environment could explain health inequalities between relatively affluent groups.