H Hemingway

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.

Relative contribution of early life and adult socioeconomic factors to adult morbidity in the Whitehall II study

STUDY OBJECTIVE To determine the relative contribution of adult compared with early life socioeconomic status as predictors of morbidity attributable to coronary heart disease (CHD), chronic bronchitis and depression in the Whitehall II study of British civil servants. DESIGN Prospective observational study with mean 5.3 years (range 3.7–7.6) follow up. SETTING 20 civil service departments originally located in London. PARTICIPANTS 6895 male and 3413 female office-based civil servants aged 35–55 years at baseline. OUTCOME MEASURES New cases at follow up of CHD, chronic bronchitis and depression defined using validated questionnaires. MAIN RESULTS Employment grade was inversely associated with CHD, chronic bronchitis and depression in men (odds ratio per unit decrease in grade 1.30, 1.44 and 1.20 respectively). Employment grade was strongly related to fathers social class. Chronic bronchitis, in women, and depression, in men, were more common among those with fathers of higher social class. When mutual adjustment was made for fathers social class, grade at entry to the civil service and current grade, the strongest effects on adult morbidity were found for current grade. Among participants in whom neither parent had died ⩽70 years of age the inverse association with adult SES was maintained. CONCLUSIONS Adult socioeconomic status was a more important predictor of morbidity attributable to coronary disease, chronic bronchitis and depression than measures of social status earlier in life. In this population, the importance of social circumstances early in life may be in the way they influence employment and social position and thus exposures in adult life.

The impact of socioeconomic status on health functioning as assessed by the SF-36 questionnaire: the Whitehall II Study.

OBJECTIVES This study measured the association between socioeconomic status and the eight scale scores of the Medical Outcomes Study short form 36 (SF-36) general health survey in the Whitehall II study of British civil servants. It also assessed, for the physical functioning scale, whether this association was independent of disease. METHODS A questionnaire containing the SF-36 was administered at the third phase of the study to 5766 men and 2589 women aged 39 through 63 years. Socioeconomic status was measured by means of six levels of employment grades. RESULTS There were significant improvements with age in general mental health, role-emotional, vitality, and social functioning scale scores. In men, all the scales except vitality showed significant age-adjusted gradients across the employment grades (lower grades, worse health). Among women, a similar relationship was found for the physical functioning, pain, and social functioning scales. For physical functioning, the effect of grade was found in those with and without disease. CONCLUSIONS Low socioeconomic status was associated with poor health functioning, and the effect sizes were comparable to those for some clinical conditions. For physical functioning, this association may act both via and independently of disease.

Is retirement good or bad for mental and physical health functioning? Whitehall II longitudinal study of civil servants

Background: To determine whether retirement at age 60 is associated with improvement or deterioration in mental and physical health, when analysed by occupational grade and gender. Methods: Longitudinal study of civil servants aged 54 to 59 years at baseline, comparing changes in SF-36 health functioning in retired (n=392) and working (n=618) participants at follow up. Data were collected from self completed questionnaires. Results: Mental health functioning deteriorated among those who continued to work, but improved among the retired. However, improvements in mental health were restricted to those in higher employment grades. Physical functioning declined in both working and retired civil servants. Conclusion: The study found that retirement at age 60 had no effects on physical health functioning and, if anything, was associated with an improvement in mental health, particularly among high socioeconomic status groups.

Does Autonomic Function Link Social Position to Coronary Risk? The Whitehall II Study

Background—Laboratory and clinical studies suggest that the autonomic nervous system responds to chronic behavioral and psychosocial stressors with adverse metabolic consequences and that this may explain the relation between low social position and high coronary risk. We sought to test this hypothesis in a healthy occupational cohort. Methods and Results—This study comprised 2197 male civil servants 45 to 68 years of age in the Whitehall II study who were undergoing standardized assessments of social position (employment grade) and the psychosocial, behavioral, and metabolic risk factors for coronary disease previously found to be associated with low social position. Five-minute recordings of heart rate variability (HRV) were used to assess cardiac parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to 0.40 Hz]) and the influence of sympathetic and parasympathetic function (low-frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low HRV (age-adjusted trend for each modality, P≤0.02). Adverse behavioral factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job control) showed age-adjusted associations with low HRV (P<0.03). The age-adjusted mean low-frequency power was 319 ms2 among those participants in the bottom tertile of job control compared with 379 ms2 in the other participants (P=0.004). HRV showed strong (P<0.001) linear associations with components of the metabolic syndrome (waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, and fasting and 2-hour postload glucose). The social gradient in prevalence of metabolic syndrome was explained statistically by adjustment for low-frequency power, behavioral factors, and job control. Conclusions—Chronically impaired autonomic function may link social position to different components of coronary risk in the general population.

Current obesity, steady weight change and weight fluctuation as predictors of physical functioning in middle aged office workers : The Whitehall II Study

OBJECTIVES: (i) To investigate the effects of current obesity, steady weight change and weight fluctuation on physical functioning and (ii) to determine whether associations are independent of coronary heart disease.DESIGN: Prospective cohort study with body mass index (BMI) measurements at four time points between the ages of 25 and 63 y.SETTING: British civil servants based in London offices at baseline.PARTICIPANTS: 6895 men and 3413 women aged 35–55 y at baseline.MAIN OUTCOME MEASURE: Physical functioning was assessed using the 10-item scale from the Short Form 36 Health Survey, with a score in the lowest quartile indicating poor physical functioning.RESULTS: After adjustment for age and confounders (employment grade, smoking, alcohol, exercise and menopausal status), current BMI was monotonically associated with poor physical functioning in women whereas a threshold effect at a BMI of 27 kg/m2 was seen in men. The odds ratio of poor physical functioning was 1.55 (95% confidence interval (CI) 1.02–2.35) amongst women and 1.04 (95% CI 0.77–1.41) amongst men with BMI 23–24.9 kg/m2 compared to those with BMI <21 kg/m2. Women in the upper, compared to the lower, tertile of steady weight change, had an odds ratio of poor physical functioning of 1.79 (1.24–2.60) after adjustment for age, confounders, current BMI and weight fluctuation. Women in the upper, compared to the lower, tertile of weight fluctuation had an odds ratio of poor physical functioning of 1.70 (1.23–2.34) adjusting for age, confounders, current BMI and steady weight change. Adjustment for the presence of coronary heart disease did not substantially alter any of these associations. Steady weight change and weight fluctuation had no independent effects in men.CONCLUSION: Among women, current obesity, steady weight change and weight fluctuation are independently and monotonically associated with poor physical functioning. Development of overt coronary heart disease is unlikely to be the mechanism for these associations.