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2.  Obesity phenotypes in midlife and cognition in early old age 
Neurology  2012;79(8):755-762.
Objective:
To examine the association of body mass index (BMI) and metabolic status with cognitive function and decline.
Methods:
A total of 6,401 adults (71.2% men), aged 39–63 years in 1991–1993, provided data on BMI (normal weight 18.5–24.9 kg/m2, overweight 25–29.9 kg/m2; and obese ≥30 kg/m2) and metabolic status (abnormality defined as 2 or more of 1) triglycerides ≥1.69 mmol/L or lipid-lowering drugs, 2) systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or antihypertensive drugs, 3) glucose ≥5.6 mmol/L or medications for diabetes, and 4) high-density lipoprotein cholesterol <1.04 mmol/L for men and <1.29 mmol/L for women). Four cognitive tests (memory, reasoning, semantic, and phonemic fluency) were administered in 1997–1999, 2002–2004, and 2007–2009, standardized to z scores, and averaged to yield a global score.
Results:
Of the participants, 31.0% had metabolic abnormalities, 52.7% were normal weight, 38.2% were overweight, and 9.1% were obese. Among the obese, the global cognitive score at baseline (p = 0.82) and decline (p = 0.19) over 10 years was similar in the metabolically normal and abnormal groups. In the metabolically normal group, the 10-year decline in the global cognitive score was similar (p for trend = 0.36) in the normal weight (−0.40; 95% confidence interval [CI] −0.42 to −0.38), overweight (−0.42; 95% CI −0.45 to −0.39), and obese (−0.42; 95% CI −0.50 to −0.34) groups. However, in the metabolically abnormal group, the decline on the global score was faster among obese (−0.49; 95% CI −0.55 to −0.42) than among normal weight individuals (−0.42; 95% CI −0.50 to −0.34), (p = 0.03).
Conclusions:
In these analyses the fastest cognitive decline was observed in those with both obesity and metabolic abnormality.
doi:10.1212/WNL.0b013e3182661f63
PMCID: PMC3421151  PMID: 22915175
4.  Influence of individual and combined healthy behaviours on successful aging 
Background:
Increases in life expectancy make it important to remain healthy for as long as possible. Our objective was to examine the extent to which healthy behaviours in midlife, separately and in combination, predict successful aging.
Methods:
We used a prospective cohort design involving 5100 men and women aged 42–63 years. Participants were free of cancer, coronary artery disease and stroke when their health behaviours were assessed in 1991–1994 as part of the Whitehall II study. We defined healthy behaviours as never smoking, moderate alcohol consumption, physical activity (≥ 2.5 h/wk moderate physical activity or ≥ 1 h/wk vigorous physical activity), and eating fruits and vegetables daily. We defined successful aging, measured over a median 16.3-year follow-up, as good cognitive, physical, respiratory and cardiovascular functioning, in addition to the absence of disability, mental health problems and chronic disease (coronary artery disease, stroke, cancer and diabetes).
Results:
At the end of follow-up, 549 participants had died and 953 qualified as aging successfully. Compared with participants who engaged in no healthy behaviours, participants engaging in all 4 healthy behaviours had 3.3 times greater odds of successful aging (95% confidence interval [CI] 2.1–5.1). The association with successful aging was linear, with the odds ratio (OR) per increment of healthy behaviour being 1.3 (95% CI 1.2–1.4; population-attributable risk for 1–4 v. 0 healthy behaviours 47%). When missing data were considered in the analysis, the results were similar to those of our main analysis.
Interpretation:
Although individual healthy behaviours are moderately associated with successful aging, their combined impact is substantial. We did not investigate the mechanisms underlying these associations, but we saw clear evidence of the importance of healthy behaviours for successful aging.
doi:10.1503/cmaj.121080
PMCID: PMC3519184  PMID: 23091184
5.  Job Strain as a Risk Factor for Leisure-Time Physical Inactivity: An Individual-Participant Meta-Analysis of Up to 170,000 Men and Women 
American Journal of Epidemiology  2012;176(12):1078-1089.
Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 1985–1988 to 2006–2008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50% women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 2–9 years. In cross-sectional analyses, the odds for physical inactivity were 26% higher (odds ratio = 1.26, 95% confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21% higher (odds ratio = 1.21, 95% confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21% and 20% higher for those with high-strain (odds ratio = 1.21, 95% confidence interval: 1.11, 1.32) and passive (odds ratio = 1.20, 95% confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.
doi:10.1093/aje/kws336
PMCID: PMC3521479  PMID: 23144364
cohort studies; exercise; physical activity; psychosocial factors; working population
6.  Differences in the association between sickness absence and long-term sub-optimal health by occupational position: a 14-year follow-up in the GAZEL cohort 
Objectives
Although sickness absence is a strong predictor of health, little work has examined whether this association varies by occupational position. The aim of this study was to investigate overall and diagnosis-specific sickness absence as a predictor of future long-term sub-optimal health by occupational position.
Methods
Prospective occupational cohort study; 15,320 employees (73% men) aged 37–51. Sickness absences (1990–1992), including 13 diagnostic categories, were examined by occupational position, based on employment grade, in relation to self-rated health measured annually 1993–2006.
Results
60% of employees in higher grade and 22% in lower grade occupations had no sickness absence. Conversely, 40% of employees in lower grade and 9.5% in higher grade occupations had over 30 sick-leave days. Repeated-measures logistic regression analyses adjusted for age, sex, and chronic disease showed employees with over 30 days absence, compared to those with no absence, had approximately double the risk of suboptimal health over the 14-year follow-up in all occupational positions. However, 1–30 days sick-leave was associated with greater odds of suboptimal health in the high; odds ratio 1.48, 95% confidence intervals (1.27–1.72) and intermediate 1.29 (1.15–1.45), but not lower grade occupations 1.06 (0.82–1.38). Differences by occupational position in the association between sickness absence in 13 specific diagnostic categories and sub-optimal health over the ensuing 14 years were limited to stronger associations observed with cancer and mental disorders in the higher grades.
Conclusions
The association between sickness absence of over 30 days a year and future long-term self-rated health appears to differ little by occupational position.
doi:10.1136/oem.2010.060210
PMCID: PMC3186885  PMID: 21242277
Sickness absence; sick leave; self-rated health; longitudinal; multi-level; occupational position
7.  Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data 
Lancet  2012;380(9852):1491-1497.
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.
doi:10.1016/S0140-6736(12)60994-5
PMCID: PMC3486012  PMID: 22981903
8.  Differences in the association between sickness absence and long-term sub-optimal health by occupational position: a 14-year follow-up in the GAZEL cohort 
Objectives
Although sickness absence is a strong predictor of health, little work has examined whether this association varies by occupational position. The aim of this study was to investigate overall and diagnosis-specific sickness absence as a predictor of future long-term sub-optimal health by occupational position.
Methods
Prospective occupational cohort study; 15,320 employees (73% men) aged 37–51. Sickness absences (1990–1992), including 13 diagnostic categories, were examined by occupational position, in relation to self-rated health measured annually 1993–2006.
Results
60% of employees in higher occupational position and 22% in lower position had no sickness absence. Conversely, 9.5% of employees in higher position and 40% in lower occupational position had over 30 sick-leave days. Repeated-measures logistic regression analyses adjusted for age, sex, and chronic disease showed employees with over 30 days absence, compared to those with no absence, had approximately double the risk of suboptimal health over the 14-year follow-up in all occupational positions. However, 1–30 days sick-leave was associated with greater odds of suboptimal health in the high; odds ratio 1.48, 95% confidence intervals (1.27–1.72) and intermediate 1.29 (1.15–1.45), but not lower occupational positions 1.06 (0.82–1.38). Differences by occupational position in the association between sickness absence in 13 specific diagnostic categories and sub-optimal health over the ensuing 14 years were limited to stronger associations observed with cancer and mental disorders in the higher occupational positions.
Conclusions
The association between sickness absence of over 30 days a year and future long-term self-rated health appears to differ little by occupational position.
doi:10.1136/oem.2010.060210
PMCID: PMC3186885  PMID: 21242277
Adult; Female; Follow-Up Studies; France; epidemiology; Health Status; Humans; Male; Middle Aged; Occupational Diseases; epidemiology; Occupational Health; statistics & numerical data; Occupations; Prospective Studies; Risk Factors; Sick Leave; statistics & numerical data; Social Class; Sickness absence; sick leave; health; longitudinal; multi-level; occupational position
9.  Does the Framingham Stroke Risk Profile predict white-matter changes in late-life depression? 
Background
Cardiovascular risk factors and diseases are important aetiological factors in depression, particularly late-life depression. Brain changes associated with vascular disease and depression can be detected using magnetic resonance imaging. Using diffusion tensor imaging (DTI), we investigated whether the Framingham stroke risk profile (FSRP), a well validated risk prediction algorithm, is associated with changes in white-matter connectivity. We hypothesised that depressed participants would show reduced white-matter integrity with higher FSRP, and non-depressed controls (matched for mean vascular risk) would show minimal co-variance with white-matter changes.
Methods
36 participants with major depression (age 71.8±7.7 years, mean FSRP 10.3±7.6) and 25 controls (age 71.8±7.3 years, mean FSRP 10.1±7.7) were clinically interviewed and examined, followed by 60-direction DTI on a 3.0 Tesla scanner. Image analysis was performed using FSL tools (www.fmrib.ox.ac.uk/fsl) to assess the correlation between FSRP and fractional anisotropy (FA). Voxelwise statistical analysis of the FA data was carried out using Tract Based Spatial Statistics. The significance threshold for correlations was set at p<0.05 using threshold-free cluster-enhancement. Partial correlation analysis investigated significant correlations in each group.
Results
Participants in the depressed group showed highly significant correlations between FSRP and FA within: body of corpus callosum (r=−0.520, p=0.002), genu of corpus callosum (r= −0.468, p=0.005), splenium of corpus callosum (r=−0.536, p=0.001) and corticospinal tract (r=−0.473, p=0.005). In controls, there was only one significant correlation in the body of corpus callosum (r=−0.473, p=0.023).
Conclusions
FSRP is associated with impairment in white-matter integrity in participants with depression; these results suggest support for the vascular depression hypothesis.
doi:10.1017/S1041610211002183
PMCID: PMC3448558  PMID: 22088779
DTI; Diffusion tensor; connectivity; vascular; depressed
10.  Association of lung function with physical, mental and cognitive function in early old age 
Age  2010;33(3):385-392.
Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV1), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50–74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta = 0.16, 95% CI: 0.13, 0.19), memory (beta = 0.09, 95% CI: 0.06, 0.12), reasoning (beta = 0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta = 0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good ‘summary’ measure of overall functioning in early old age.
doi:10.1007/s11357-010-9189-x
PMCID: PMC3168608  PMID: 20878489
Ageing; Lung function; Cognitive function; Physical function
11.  Combined Effects of Depressive Symptoms and Resting Heart Rate on Mortality: The Whitehall II Prospective Cohort Study 
The Journal of clinical psychiatry  2010;72(9):1199-1206.
Objective
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Methods
Data come from 5936 participants, aged 61 ± 6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥ 16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60 – 80, >80 bpm). Mean follow-up for mortality was 5.6 years.
Results
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
Conclusions
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
doi:10.4088/JCP.09m05901blu
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
12.  Association of lung function with physical, mental and cognitive function in early old age 
Age  2010;33(3):385-392.
Lung function predicts mortality, whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in one second, height FEV1), walking speed (over 2.44 m), cognitive function (memory and reasoning), and self-reported physical and mental functioning (SF-36) were available on 4443 individuals, aged 50–74 years. In models adjusted for age, one standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19), and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), BMI and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good “summary” measure of overall functioning in early old age.
doi:10.1007/s11357-010-9189-x
PMCID: PMC3168608  PMID: 20878489
Aged; Aging; physiology; psychology; Cognition; physiology; Female; Health Status; Humans; Lung; physiology; Male; Middle Aged; Spirometry; Walking; physiology; ageing; lung function; cognitive function; physical function
13.  Does cognitive reserve shape cognitive decline? 
Annals of neurology  2011;70(2):296-304.
Objectives
Cognitive reserve is associated with a lower risk of dementia but the extent to which it shapes cognitive aging trajectories remains unclear. Our objective is to examine the impact of three markers of reserve from different points in the lifecourse on cognitive function and decline in late adulthood.
Methods
Data are from 5234 men and 2220 women, mean age 56 years (standard deviation=6) at baseline, from the Whitehall II cohort study. Memory, reasoning, vocabulary, phonemic and semantic fluency were assessed three times over 10 years. Linear mixed models were used to assess the association between markers of reserve (height, education, and occupation) and cognitive decline, using the 5 cognitive tests and a global cognitive score composed of these tests.
Results
All three reserve measures were associated with baseline cognitive function, with strongest associations with occupation and the weakest with height. All cognitive functions except vocabulary declined over the 10 year follow-up period. On the global cognitive test, there was greater decline in the high occupation group (−0.27; 95% confidence interval (CI): −0.28, −0.26) compared to the intermediate (−0.23; 95% CI: −0.25, −0.22) and low groups (−0.21; 95% CI: −0.24, −0.19); p=0.001. The decline in reserve groups defined by education (p=0.82) and height (p=0.55) was similar.
Interpretation
Cognitive performance over the adult lifecourse was remarkably higher in the high reserve groups. However, rate of cognitive decline did not differ between reserve groups except occupation where there was some evidence of greater decline in the high occupation group.
doi:10.1002/ana.22391
PMCID: PMC3152621  PMID: 21563209
14.  Natural Course of Recurrent Psychological Distress in Adulthood 
Journal of affective disorders  2010;130(3):454-461.
Background
The course of major depressive disorder is often characterized by progressing chronicity, but whether this applies to the course of self-reported psychological distress remains unclear. We examined whether the risk of self-reported psychological distress becomes progressively higher the longer the history of distress and whether prolonged history of distress modifies associations between risk markers and future distress.
Methods
Participants were British civil servants from the prospective Whitehall II cohort study (n=7934; 31.5% women, mean age 44.5 years at baseline) followed from 1985 to 2006 with repeat data collected in 7 study phases. Psychological distress was assessed with the 30-item General Health Questionnaire (GHQ). Sex, socioeconomic status, marital status, ethnicity, physical activity, alcohol consumption, smoking, and obesity were assessed as risk markers.
Results
Recurrent history of psychological distress was associated with a progressively increasing risk of future distress in a dose-response manner. Common risk markers, such as low socioeconomic status, non-White ethnicity, being single, and alcohol abstinence were stronger predictors of subsequent distress in participants with a longer history of psychological distress. Sex differences in psychological distress attenuated with prolonged distress history.
Limitations
The participants were already adults in the beginning of the study, so we could not assess the progressive chronicity of psychological distress from adolescence onwards.
Conclusions
These data suggest that self-reported psychological distress becomes more persistent over time and that a longer prior exposure to psychological distress increases sensitivity to the stressful effects of certain risk markers.
doi:10.1016/j.jad.2010.10.047
PMCID: PMC3062710  PMID: 21106248
Chronic distress; Kindling hypothesis; Longitudinal; Recurrence
15.  Socioeconomic Status, Structural and Functional Measures of Social Support, and Mortality 
American Journal of Epidemiology  2012;175(12):1275-1283.
The authors examined the associations of social support with socioeconomic status (SES) and with mortality, as well as how SES differences in social support might account for SES differences in mortality. Analyses were based on 9,333 participants from the British Whitehall II Study cohort, a longitudinal cohort established in 1985 among London-based civil servants who were 35–55 years of age at baseline. SES was assessed using participant's employment grades at baseline. Social support was assessed 3 times in the 24.4-year period during which participants were monitored for death. In men, marital status, and to a lesser extent network score (but not low perceived support or high negative aspects of close relationships), predicted both all-cause and cardiovascular mortality. Measures of social support were not associated with cancer mortality. Men in the lowest SES category had an increased risk of death compared with those in the highest category (for all-cause mortality, hazard ratio = 1.59, 95% confidence interval: 1.21, 2.08; for cardiovascular mortality, hazard ratio = 2.48, 95% confidence interval: 1.55, 3.92). Network score and marital status combined explained 27% (95% confidence interval: 14, 43) and 29% (95% confidence interval: 17, 52) of the associations between SES and all-cause and cardiovascular mortality, respectively. In women, there was no consistent association between social support indicators and mortality. The present study suggests that in men, social isolation is not only an important risk factor for mortality but is also likely to contribute to differences in mortality by SES.
doi:10.1093/aje/kwr461
PMCID: PMC3372313  PMID: 22534202
cohort; longitudinal; mortality; social class; social support
16.  Influence of retirement and work stress on headache prevalence: a longitudinal modelling study from the GAZEL Cohort Study 
Cephalalgia  2011;31(6):696-705.
Aims
To examine trajectories of headache in relation to retirement and to clarify the role of work stress and stress-prone personality.
Methods
Headache prevalence during seven years before and after retirement was measured by annual questionnaires from GAZEL cohort comprising French national gas and electricity company employees (N=12,913). Odds ratios and 95% confidence intervals for headache during pre- peri- and post-retirement were calculated. The role of effect modifiers (work stress, type A or hostile personality) was tested by multiplicative interactions and synergy indices.
Results
11%–13% reduction in headache prevalence was found during pre- and post-retirement, whereas decline was much steeper (46%) during the retirement transition. In absolute terms, the decline was greater among persons with high work stress or stress-prone personality than among other participants.
Conclusions
Retirement is associated with a decrease in headache prevalence, particularly among persons with high amount of work stress or proneness to overreact to stress.
doi:10.1177/0333102410394677
PMCID: PMC3317892  PMID: 21220374
headache; retirement; work stress; stress-prone personality
17.  INFLUENCE OF RETIREMENT AND WORK STRESS ON HEADACHE PREVALENCE: A LONGITUDINAL MODELLING STUDY FROM THE GAZEL COHORT 
Cephalalgia  2011;31(6):696-705.
Aims
To examine trajectories of headache in relation to retirement and to clarify the role of work stress and stress-prone personality.
Methods
Headache prevalence during seven years before and after retirement was measured by annual questionnaires from GAZEL cohort comprising French national gas and electricity company employees (N=12,913). Odds ratios and 95% confidence intervals for headache during pre- peri- and post-retirement were calculated. The role of effect modifiers (work stress, type A or hostile personality) was tested by multiplicative interactions and synergy indices.
Results
11%-13% reduction in headache prevalence was found during pre- and post-retirement, whereas decline was much steeper (46%) during the retirement transition. In absolute terms, the decline was greater among persons with high work stress or stress-prone personality than among other participants.
Conclusions
Retirement is associated with a decrease in headache prevalence, particularly among persons with high amount of work stress or proneness to overreact to stress.
doi:10.1177/0333102410394677
PMCID: PMC3317892  PMID: 21220374
headache; retirement; work stress; stress-prone personality
18.  TRAJECTORIES OF DEPRESSIVE EPISODES AND HYPERTENSION OVER 24 YEARS: THE WHITEHALL II PROSPECTIVE COHORT STUDY 
Hypertension  2011;57(4):710-716.
Prospective data on depressive symptoms and blood pressure (BP) are scarce, and the impact of age on this association is poorly understood. The present study examines longitudinal trajectories of depressive episodes and the probability of hypertension associated with these trajectories over time. Participants were 6,889 men and 3,413 women London based civil servants, aged 35–55 years at baseline, followed for 24 years between 1985 and 2009. Depressive episode (defined as scoring 4 or more on the General Health Questionnaire-Depression subscale or using prescribed antidepressant medication) and hypertension (systolic/diastolic blood pressure ≥ 140/90 mm Hg or use of antihypertensive medication) were assessed concurrently at five medical examinations. In the fully adjusted longitudinal logistic regression analyses based on Generalized-Estimating-Equations using age as the time scale, participants in the “increasing depression” group had a 24% (p<0.05) lower risk of hypertension at ages 35–39, compared to those in the “low/transient depression” group. However, there was a faster age-related increase in hypertension in the “increasing depression” group, corresponding to a 7% (p<0.01) greater increase in the odds of hypertension for every each five-year increase in age. A higher risk of hypertension in the first group of participants was not evident before age 55. A similar pattern of association was observed in men and women although it was stronger in men. This study suggests that the risk of hypertension increases with repeated experience of depressive episodes over time and becomes evident in later adulthood.
doi:10.1161/HYPERTENSIONAHA.110.164061
PMCID: PMC3065997  PMID: 21339474
Depression; hypertension; longitudinal analysis; repeated measures
19.  Combined effects of depressive symptoms and resting heart rate on mortality: the Whitehall II prospective cohort study 
The Journal of Clinical Psychiatry  2010;72(9):1199-1206.
Objective
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Methods
Data come from 5936 participants, aged 61 ±6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60–80, >80 bpm). Mean follow-up for mortality was 5.6 years.
Results
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
Conclusions
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
doi:10.4088/JCP.09m05901blu
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
20.  Do different measures of early life socioeconomic circumstances predict adult mortality? Evidence from the British Whitehall II and French GAZEL studies 
Background
Father’s occupational position, education and height have all been used to examine the effects of adverse early life socioeconomic circumstances on health, but it remains unknown whether they predict mortality equally well.
Methods
We used pooled data on 18393 men and 7060 women from the Whitehall-II and GAZEL cohorts to examine associations between early life socioeconomic circumstances and all-cause and cause-specific mortality.
Results
During the 20-year follow-up period, 1487 participants died. Education had a monotonic association with all mortality outcomes, the age, sex and cohort adjusted Hazard Ratio (HR) for the lowest versus the highest educational group was 1.45 (95% Confidence Interval (CI): 1.24,1.69) for all-cause mortality. There was evidence of a U-shaped association between height and all-cause, cancer and cardiovascular mortality, robust to adjustment for the other indicators (HR=1.41; 95% CI: 1.03,1.93 for those shorter-than-average and HR=1.36; 95% CI: 0.98,1.88 for those taller-than-average for cardiovascular (CVD) mortality). Greater all-cause and cancer mortality was observed in participants whose father’s occupational position was manual rather than non-manual (HR=1.11; 95% CI: 1.00,1.23 for all-cause mortality), but the risks were attenuated after adjusting for education and height.
Conclusions
The association between early life socioeconomic circumstances and mortality depends on the socioeconomic indicator used and the cause of death examined. Height is not a straightforward measure of early life socioeconomic circumstances as taller people do not have a health advantage for all mortality outcomes.
doi:10.1136/jech.2009.102376
PMCID: PMC3294283  PMID: 20675701
Body height; early life; cohort studies; education; mortality; occupational position; Adult; Aged; Cardiovascular Diseases; mortality; Cause of Death; Cohort Studies; Female; Follow-Up Studies; France; epidemiology; Great Britain; epidemiology; Humans; Male; Middle Aged; Neoplasms; mortality; Occupations; Proportional Hazards Models; Risk; Risk Factors; Social Class
21.  Long working hours and symptoms of anxiety and depression: a 5-year follow-up of the Whitehall II study 
Background
Although long working hours are common in working populations, little is known about the effect of long working hours on mental health.
Method
We examined the association between long working hours and onset of depressive and anxiety symptoms in middle-aged employees. Participants were 2960 full-time employees aged 44 to 66 (2248 men, 712 women) from the prospective Whitehall II cohort study of British civil servants. Working hours, anxiety and depressive symptoms, and covariates were measured at baseline (1997–1999) followed by two subsequent measurements of depressive and anxiety symptoms (2001 and 2002–2004).
Results
In prospective analysis of participants with no depressive symptoms (n=2549) or anxiety symptoms (n=2618) at baseline, Cox proportional hazard analysis adjusted for baseline covariates showed a 1.66-fold (95% CI 1.06–2.61) risk of depressive symptoms and a 1.74-fold (1.15–2.61) risk of anxiety symptoms among employees working more than 55 hours a week compared with employees working 35–40 hours a week. Sex-stratified analysis showed an excess risk of depression and anxiety associated with long working hours among women [hazard ratios 2.67 (1.07–6.68) and 2.84 (1.27–6.34)] but not men [1.30 (0.77–2.19) and 1.43 (0.89–2.30)].
Conclusions
Working long hours is a risk factor for development of depressive and anxiety symptoms in women.
doi:10.1017/S0033291711000171
PMCID: PMC3095591  PMID: 21329557
Work hours; depression; anxiety; overtime work; prospective
22.  Examining Overweight and Obesity as Risk Factors for Common Mental Disorders Using Fat Mass and Obesity-Associated (FTO) Genotype-Instrumented Analysis 
American Journal of Epidemiology  2011;173(4):421-429.
The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)2). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study (London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985–2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men—a finding that should be interpreted cautiously because the function of the FTO gene is unknown.
doi:10.1093/aje/kwq444
PMCID: PMC3032807  PMID: 21248310
anxiety; body mass index; depression; Mendelian randomization analysis; mental health; obesity; risk factors
23.  Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort 
European heart journal  2011;33(4):478-485.
Aims
To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women.
Methods and results
From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age–sex-adjusted hazard of MI fell by 74% (95% confidence interval 48–87%), corresponding to an average annual decline of 6.5% (3.2–9.7%). Thirty-four per cent (20–76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10–32%), reduced systolic blood pressure (13%, 7–24%), and reduced cigarette smoking prevalence (6%, 2–14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (−1–20%). In combination, these five risk factors explained 56% (34–112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5–23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women.
Conclusion
In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.
doi:10.1093/eurheartj/ehr142
PMCID: PMC3272419  PMID: 21653562
Myocardial infarction; Incidence; Time Trends; Population; Prevention; Risk factors
24.  Change in physical activity and weight in relation to retirement: the French GAZEL Cohort Study 
BMJ Open  2012;2(1):e000522.
Objectives
To examine the trajectories of physical activity from preretirement to postretirement and to further clarify whether the changes in physical activity are associated with changes in body weight.
Design
Prospective.
Setting
French national gas and electricity company (GAZEL cohort).
Participants
From the original sample of 20 625 employees, only those retiring between 2001 and 2008 on a statutory basis were selected for the analyses (analysis 1: n=2711, 63% men; analysis 2: n=3812, 75% men). Persons with data on at least one preretirement and postretirement measurement of the outcome were selected.
Primary and secondary outcome measures
All outcome data were gathered by questionnaires. In analysis 1, the annual prevalence of higher physical activity (walking ≥5 km/week) 4 years before and after retirement was analysed. In analysis 2, changes in leisure-time sport activities (engagement, frequency and manner) from preretirement to postretirement were analysed with simultaneous changes in body weight (kilogram).
Results
In analysis 1 (n=2711), prevalence estimates for 4 years before and 4 years after retirement showed that higher leisure-time physical activity (walking at least 5 km/week) increased by 36% in men and 61% in women during the transition to retirement. This increase was also observed among people at a higher risk of physical inactivity, such as smokers and those with elevated depressive symptoms. In a separate sample (analysis 2, n=3812), change in weight as a function of preretirement and postretirement physical activity was analysed. Weight gain preretirement to postretirement was 0.85 (95% CI 0.48 to 1.21) to 1.35 (0.79 to 1.90) kg greater among physically inactive persons (decrease in activity or inactive) compared with those physically active (p<0.001).
Conclusions
Retirement transition may be associated with beneficial changes in lifestyle and may thus be a good starting point to preventive interventions in various groups of individuals in order to maintain long-term changes.
Article summary
Article focus
The main focus of this article was to examine whether statutory retirement is associated with changes in physical activity.
Especially, we wanted to clarify what happens during the actual retirement transition (ie, the year of retirement ±1 year).
Furthermore, we examined whether there were changes in body weight as a function of preretirement and postretirement physical activity level.
Key messages
We were able to show that during a 9-year follow-up physical activity increased most during the retirement transition, both in men and women.
Beneficial changes were noticed also among those usually considered as low physical activity groups, such as smokers.
Physically inactive persons were most prone to gain weight during the follow-up.
Strengths and limitations of this study
The main strength of this study was yearly measurements of the outcome, which enabled us to get accurate estimates of physical activity during the actual retirement transition.
Large and stable occupational cohort, prospective study design, accurate register-based data on retirement and long follow-up both preretirement and postretirement were other strengths of this study.
The main limitation was the use of self-report data of the outcome.
doi:10.1136/bmjopen-2011-000522
PMCID: PMC3277904  PMID: 22318663
Body weight changes; exercise; longitudinal studies; retirement
25.  Comparison of alternative versions of the job demand-control scales in 17 European cohort studies: the IPD-Work consortium 
BMC Public Health  2012;12:62.
Background
Job strain (i.e., high job demands combined with low job control) is a frequently used indicator of harmful work stress, but studies have often used partial versions of the complete multi-item job demands and control scales. Understanding whether the different instruments assess the same underlying concepts has crucial implications for the interpretation of findings across studies, harmonisation of multi-cohort data for pooled analyses, and design of future studies. As part of the 'IPD-Work' (Individual-participant-data meta-analysis in working populations) consortium, we compared different versions of the demands and control scales available in 17 European cohort studies.
Methods
Six of the 17 studies had information on the complete scales and 11 on partial scales. Here, we analyse individual level data from 70 751 participants of the studies which had complete scales (5 demand items, 6 job control items).
Results
We found high Pearson correlation coefficients between complete scales of job demands and control relative to scales with at least three items (r > 0.90) and for partial scales with two items only (r = 0.76-0.88). In comparison with scores from the complete scales, the agreement between job strain definitions was very good when only one item was missing in either the demands or the control scale (kappa > 0.80); good for job strain assessed with three demand items and all six control items (kappa > 0.68) and moderate to good when items were missing from both scales (kappa = 0.54-0.76). The sensitivity was > 0.80 when only one item was missing from either scale, decreasing when several items were missing in one or both job strain subscales.
Conclusions
Partial job demand and job control scales with at least half of the items of the complete scales, and job strain indices based on one complete and one partial scale, seemed to assess the same underlying concepts as the complete survey instruments.
doi:10.1186/1471-2458-12-62
PMCID: PMC3328260  PMID: 22264402
Job demands; Job control; Job strain; Work stress; Agreement

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