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1.  Informal Caregiving and the Risk for Coronary Heart Disease: The Whitehall II Study 
Background.
The stress associated with informal caregiving has been shown to be associated with poor health, including coronary heart disease (CHD). However, it is unclear if the risk of CHD is attributable to caregiving or prior poor health of the caregiver.
Methods.
We used data from the Whitehall II cohort study. Caregiving and caregiver’s health (using 3 measures: self-rated health, mental health using the General Health Questionnaire, and physical component score of the SF-36) were assessed in 1991–1993 among 5,468 men and 2,457 women aged 39–63 years. CHD (fatal CHD, clinically verified nonfatal myocardial infarction, and definite angina) incidence was recorded for a mean 17 years; sociodemographic variables, health behaviors, and cardiovascular risk factors were included as covariates.
Results.
Cox regression showed the risk of CHD in caregivers not to be higher (hazard ratio = 1.18; 95% CI: 0.96, 1.45) compared with noncaregivers. Analyses stratified by health status showed that compared with noncaregivers in good health, caregivers with poor self-rated (hazard ratio = 2.00; 95% CI: 1.44, 2.78), mental (hazard ratio = 1.63; 95% CI: 1.16, 2.30), or physical (hazard ratio =1.87; 95% CI: 1.34, 2.62) health had greater risk of CHD. A similar elevated risk was observed in noncaregivers with poor health; no excess risk was observed among caregivers reporting good health, and the combined effect of poor health and caregiving did not exceed their independent effects.
Conclusions.
Caregiving in midlife is not in itself associated with greater risk of CHD, but it is associated with increased risk for CHD among caregivers who report being in poor health.
doi:10.1093/gerona/glt025
PMCID: PMC3779628  PMID: 23525476
Coronary heart disease; Stress; Caregiver.
2.  Bidirectional association between physical activity and symptoms of anxiety and depression: the Whitehall II study 
European journal of epidemiology  2012;27(7):537-546.
Although it has been hypothesized that the association of physical activity with depressive and anxiety symptoms is bidirectional, few studies have examined this issue in a prospective setting. We studied this bidirectional association using data on physical activity and symptoms of anxiety and depression at three points in time over 8 years. A total of 9,309 participants of the British Whitehall II prospective cohort study provided data on physical activity, anxiety and depression symptoms and 10 covariates at baseline in 1985. We analysed the associations of physical activity with anxiety and/or depression symptoms using multinomial logistic regression (with anxiety and depression symptoms as dependent variables) and binary logistic regression (with physical activity as the dependent variable). There was a cross-sectional inverse association between physical activity and anxiety and/or depressive symptoms at baseline (ORs between 0.63 and 0.72). In cumulative analyses, regular physical activity across all three data waves, but not irregular physical activity, was associated with reduced likelihood of depressive symptoms at follow-up (OR = 0.71, 95 % CI 0.54, 0.99). In a converse analysis, participants with anxiety and depression symptoms at baseline had higher odds of not meeting the recommended levels of physical activity at follow-up (OR = 1.79, 95 % CI 1.17, 2.74). This was also the case in individuals with anxiety and/or depression symptoms at both baseline and follow-up (OR = 1.70, 95 % CI 1.10, 2.63). The association between physical activity and symptoms of anxiety and/or depression appears to be bidirectional.
doi:10.1007/s10654-012-9692-8
PMCID: PMC4180054  PMID: 22623145
Common mental disorders; Physical activity; Bidirectional association; Longitudinal studies
3.  Increased risk of coronary heart disease among individuals reporting adverse impact of stress on their health: the Whitehall II prospective cohort study 
European Heart Journal  2013;34(34):2697-2705.
Aim
Response to stress can vary greatly between individuals. However, it remains unknown whether perceived impact of stress on health is associated with adverse health outcomes. We examined whether individuals who report that stress adversely affects their health are at increased risk of coronary heart disease (CHD) compared with those who report that stress has no adverse health impact.
Methods and results
Analyses are based on 7268 men and women (mean age: 49.5 years, interquartile range: 11 years) from the British Whitehall II cohort study. Over 18 years of follow-up, there were 352 coronary deaths or first non-fatal myocardial infarction (MI) events. After adjustment for sociodemographic characteristics, participants who reported at baseline that stress has affected their health ‘a lot or extremely’ had a 2.12 times higher (95% CI 1.52–2.98) risk of coronary death or incident non-fatal MI when compared with those who reported no effect of stress on their health. This association was attenuated but remained statistically significant after adjustment for biological, behavioural, and other psychological risk factors including perceived stress levels, and measures of social support; fully adjusted hazard ratio: 1.49 (95% CI 1.01–2.22).
Conclusions
In this prospective cohort study, the perception that stress affects health, different from perceived stress levels, was associated with an increased risk of coronary heart disease. Randomized controlled trials are needed to determine whether disease risk can be reduced by increasing clinical attention to those who complain that stress greatly affects their health.
doi:10.1093/eurheartj/eht216
PMCID: PMC3766148  PMID: 23804585
Epidemiology; Stress; Coronary heart disease; Prospective studies
4.  Personality and All-Cause Mortality: Individual-Participant Meta-Analysis of 3,947 Deaths in 76,150 Adults 
American Journal of Epidemiology  2013;178(5):667-675.
Personality may influence the risk of death, but the evidence remains inconsistent. We examined associations between personality traits of the five-factor model (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) and the risk of death from all causes through individual-participant meta-analysis of 76,150 participants from 7 cohorts (the British Household Panel Survey, 2006–2009; the German Socio-Economic Panel Study, 2005–2010; the Household, Income and Labour Dynamics in Australia Survey, 2006–2010; the US Health and Retirement Study, 2006–2010; the Midlife in the United States Study, 1995–2004; and the Wisconsin Longitudinal Study's graduate and sibling samples, 1993–2009). During 444,770 person-years at risk, 3,947 participants (54.4% women) died (mean age at baseline = 50.9 years; mean follow-up = 5.9 years). Only low conscientiousness—reflecting low persistence, poor self-control, and lack of long-term planning—was associated with elevated mortality risk when taking into account age, sex, ethnicity/nationality, and all 5 personality traits. Individuals in the lowest tertile of conscientiousness had a 1.4 times higher risk of death (hazard ratio = 1.37, 95% confidence interval: 1.18, 1.58) compared with individuals in the top 2 tertiles. This association remained after further adjustment for health behaviors, marital status, and education. In conclusion, of the higher-order personality traits measured by the five-factor model, only conscientiousness appears to be related to mortality risk across populations.
doi:10.1093/aje/kwt170
PMCID: PMC3755650  PMID: 23911610
meta-analysis; mortality; personality; psychology; survival analysis
5.  Personality and the risk of cancer: a 16-year follow-up study of the GAZEL cohort 
Psychosomatic Medicine  2013;75(3):262-271.
Objective
Large-scale prospective studies do not support an association between neuroticism and extroversion with cancer incidence. However, research on other personality constructs is inconclusive. This longitudinal study examined the associations between four personality measures, Type 1 “suppressed emotional expression,” Type 5 “rational/anti-emotional,” hostility and Type A with cancer incidence.
Methods
Personality measures were available for 13,768 members in the GAZEL cohort study (baseline assessment in 1993). Follow-up for diagnoses of primary cancers was obtained from January 1, 1994 to December 31, 2009. Associations between personality and cancer incidence were evaluated using Cox proportional hazards analyses and adjusted for potential confounders.
Results
During a median follow-up of 16.0 years [range: 9 days-16 years], 1,139 participants received at least one diagnosis of primary cancer. The mean duration between baseline and cancer diagnosis was 9.3 years. Type 1 personality was associated with a decreased risk of breast cancer [hazard ratio (HR) per standard deviation: 0.81, 95% confidence interval (CI) = 0.68–0.97, p=.02]. Type 5 personality was not associated with prostate, breast, colorectal or smoking-related cancers, but was associated with other cancers (HR per standard deviation: 1.17, 95% CI = 1.04–1.31, p=.01). Hostility was associated with an increased risk of smoking-related cancers, which was explained by smoking habits, and Type A was not associated with any of the cancer end-points.
Conclusions
Several personality measures were prospectively associated with the incidence of selected cancers. These links may warrant further epidemiological studies and investigations about potential biobehavioral mechanisms.
doi:10.1097/PSY.0b013e31828b5366
PMCID: PMC3977138  PMID: 23513238
Adult; Cohort Studies; Female; Follow-Up Studies; France; epidemiology; Hostility; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Neoplasms; epidemiology; psychology; Personality; Personality Inventory; statistics & numerical data; Proportional Hazards Models; Prospective Studies; Registries; statistics & numerical data; Risk; Risk Factors; Emotion; Epidemiology; Incidence; Personality; Risk; Cancer
6.  Trajectories of the Framingham general cardiovascular risk profile in midlife and poor motor function later in life: The Whitehall II study☆☆☆ 
Background
Vascular risk factors are associated with increased risk of cognitive impairment and dementia, but their association with motor function, another key feature of aging, has received little research attention. We examined the association between trajectories of the Framingham general cardiovascular disease risk score (FRS) over midlife and motor function later in life.
Methods
A total of 5376 participants of the Whitehall II cohort study (29% women) who had up to four repeat measures of FRS between 1991–1993 (mean age = 48.6 years) and 2007–2009 (mean age = 65.4 years) and without history of stroke or coronary heart disease in 2007–2009 were included. Motor function was assessed in 2007–2009 through objective tests (walking speed, chair rises, balance, finger tapping, grip strength). We used age- and sex-adjusted linear mixed models.
Results
Participants with poorer performances for walking speed, chair rises, and balance in 2007–2009 had higher FRS concurrently and also in 1991–1993, on average 16 years earlier. These associations were robust to adjustment for cognition, socio-economic status, height, and BMI, and not explained by incident mobility limitation prior to motor assessment. No association was found with finger tapping and grip strength.
Conclusions
Cardiovascular risk early in midlife is associated with poor motor performances later in life. Vascular risk factors play an important and under-recognized role in motor function, independently of their impact on cognition, and suggest that better control of vascular risk factors in midlife may prevent physical impairment and disability in the elderly.
doi:10.1016/j.ijcard.2013.12.051
PMCID: PMC3991855  PMID: 24461963
CVD, cardiovascular disease; FRS, Framingham general cardiovascular disease risk score; SES, socioeconomic status; BMI, body mass index; SD, standard deviation; Cardiovascular risk score; Motor function; Aging; Stroke; Cohort study
7.  Low Conscientiousness and Risk of All-Cause, Cardiovascular and Cancer Mortality over 17 Years: Whitehall II Cohort Study 
Objective
To examine the personality trait conscientiousness as a risk factor for mortality and to identify candidate explanatory mechanisms.
Methods
Participants in the Whitehall II cohort study (N = 6800, aged 34 to 55 at recruitment in 1985) completed two self-reported items measuring conscientiousness in 1991–1993 (‘I am overly conscientious’ and ‘I am overly perfectionistic’, Cronbach's α = .72), the baseline for this study. Age, socio-economic status (SES), social support, health behaviours, physiological variables and minor psychiatric morbidity were also recorded at baseline. The vital status of participants was then monitored for a mean of 17 years. All-cause and cause-specific mortality was ascertained through linkage to a national mortality register until January 2010.
Results
Each 1 standard deviation decrease in conscientiousness was associated with a 10% increase in all-cause (hazard ratio [HR] = 1.10, 95% CI 1.003, 1.20) mortality. Patterns were similar for cardiovascular (HR = 1.17, 95% CI 0.98, 1.39) and cancer mortality (HR = 1.10, 95% CI 0.96, 1.25), not reaching statistical significance. The association with all-cause mortality was attenuated by 5% after adjustment for SES, 13% for health behaviours, 14% for cardiovascular risk factors, 5% for minor psychiatric morbidity, 29% for all variables. Repeating analyses with each item separately and excluding participants who died within five years of personality assessment did not change the results materially.
Conclusion
Low conscientiousness in midlife is a risk factor for all-cause mortality. This association is only partly explained by health behaviours, SES, cardiovascular disease risk factors and minor psychiatric morbidity in midlife.
doi:10.1016/j.jpsychores.2012.05.007
PMCID: PMC3936113  PMID: 22789411
cohort study; conscientiousness; mortality; perfectionism; personality traits; socio-economic status
8.  Influence of retirement on nonadherence to medication for hypertension and diabetes 
Background:
The extent to which common life transitions influence medication adherence among patients remains unknown. We examined whether retirement is associated with a change in adherence to medication in patients with hypertension or type 2 diabetes.
Methods:
Participants in the Finnish Public Sector study were linked to national registers. We included data for the years 1994–2011. We identified and followed 3468 adult patients with hypertension and 412 adult patients with type 2 diabetes for medication adherence for the 3 years before their retirement and the 4 years after their retirement (mean follow-up 6.8 yr). Our primary outcome was proportion of patients with poor adherence to medication, which we defined as less than 40% of days covered by treatment. We determined these proportions before and after retirement using data from filled prescriptions.
Results:
The preretirement prevalence of poor adherence to medication was 6% in men and women with hypertension, 2% in men with diabetes and 4% in women with diabetes. Among men, retirement was associated with an increased risk of poor adherence to both antihypertensive agents (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.68) and antidiabetic drugs (OR 2.40, 95% CI 1.37–4.20). Among women, an increased risk of poor adherence was seen only for antihypertensive agents (OR 1.25, 95% CI 1.07–1.46). Similar results were apparent for alternative definitions of poor adherence. Our results did not differ across strata of age, socioeconomic status or comorbidity.
Interpretation:
We found a decline in adherence to medication after retirement among men and women with hypertension and men with type 2 diabetes. If these findings can be confirmed, we need randomized controlled trials to determine whether interventions to reduce poor adherence after retirement could improve clinical outcomes of treatments for hypertension and diabetes.
doi:10.1503/cmaj.122010
PMCID: PMC3832579  PMID: 24082018
9.  Usefulness of a single-item measure of depression to predict mortality: the GAZEL prospective cohort study 
Background: It remains unknown whether short measures of depression perform as well as long measures in predicting adverse outcomes such as mortality. The present study aims to examine the predictive value of a single-item measure of depression for mortality. Methods: A total of 14 185 participants of the GAZEL cohort completed the 20-item Center-for-Epidemiologic-Studies-Depression (CES-D) scale in 1996. One of these items (I felt depressed) was used as a single-item measure of depression. All-cause mortality data were available until 30 September 2009, a mean follow-up period of 12.7 years with a total of 650 deaths. Results: In Cox regression model adjusted for baseline socio-demographic characteristics, a one-unit increase in the single-item score (range 0–3) was associated with a 25% higher risk of all-cause mortality (95% CI: 13–37%, P < 0.001). Further adjustment for health-related behaviours and physical chronic diseases reduced this risk by 36% and 8%, respectively. After adjustment for all these variables, every one-unit increase in the single-item score predicted a 15% increased risk of death (95% CI: 5–27%, P < 0.01). There is also an evidence of a dose–reponse relationship between reponse scores on the single-item measure of depression and mortality. Conclusion: This study shows that a single-item measure of depression is associated with an increased risk of death. Given its simplicity and ease of administration, a very simple single-item measure of depression might be useful for identifying middle-aged adults at risk for elevated depressive symptoms in large epidemiological studies and clinical settings.
doi:10.1093/eurpub/ckr103
PMCID: PMC3457003  PMID: 21840893
10.  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
11.  Association between Dietary Patterns and Depressive Symptoms Over Time: A 10-Year Follow-Up Study of the GAZEL Cohort 
PLoS ONE  2012;7(12):e51593.
Background
Data on the association between dietary patterns and depression are scarce. The objective of this study was to examine the longitudinal association between dietary patterns and depressive symptoms assessed repeatedly over 10 years in the French occupational GAZEL cohort.
Methods
A total of 9,272 men and 3,132 women, aged 45–60 years in 1998, completed a 35-item Food Frequency Questionnaire (FFQ) at baseline. Dietary patterns were derived by Principal Component Analysis. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression scale (CES-D) in 1999, 2002, 2005 and 2008. The main outcome measure was the repeated measures of CES-D. Longitudinal analyses were performed with logistic regression based on generalized estimating equations.
Principal Findings
The highest quartile of low-fat, western, high snack and high fat-sweet diets in men and low-fat and high snack diets in women were associated with higher likelihood of depressive symptoms at the start of the follow-up compared to the lowest quartile (OR between 1.16 and 1.50). Conversely, the highest quartile of traditional diet (characterized by fish and fruit consumption) was associated with a lower likelihood of depressive symptoms in women compared to the lowest quartile, with OR = 0.63 [95%CI, 0.50 to 0.80], as the healthy pattern (characterized by vegetables consumption) with OR = 0.72 [95%CI, 0.63 to 0.83] and OR = 0.75 [95%CI, 0.61 to 0.93] in men and women, respectively. However, there was probably a reverse causality effect for the healthy pattern.
Conclusion
This longitudinal study shows that several dietary patterns are associated with depressive symptoms and these associations track over time.
doi:10.1371/journal.pone.0051593
PMCID: PMC3520961  PMID: 23251585
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 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
13.  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
14.  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
15.  Letter by Nabi regarding article, "attained educational level and incident atherothrombotic events in low- and middle-income compared with high-income countries" 
Circulation  2011;123(20):e605; author reply e606.
doi:10.1161/CIRCULATIONAHA.110.000133
PMCID: PMC3348122  PMID: 21606403
Coronary Artery Disease; epidemiology; Developing Countries; statistics & numerical data; Educational Status; Humans; Incidence; Income; statistics & numerical data; Peripheral Vascular Diseases; epidemiology; Risk Factors; Socioeconomic Factors
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.  Lost work days in the 6 years leading to premature death from cardiovascular disease in men and women 
Atherosclerosis  2010;211(2):689-693.
Background
It is unclear whether individuals experience specific patterns of morbidity prior to premature death from cardiovascular disease (CVD).
Methods
We examined morbidity levels in the 6 years leading up to death from CVD in 37,397 men and 113,198 women under 65 years of age from the Finnish Public Sector study, with a particular focus on gender differences. Morbidity was assessed using lost days from work, extracted from register data on sickness leave and disability pension. Data on cause-specific mortality were obtained from national health registers.
Results
During a median follow-up of 8.5 years, there were 361 CVD deaths (174 from ischemic heart disease (ICD9 410-414, 427.5; ICD10 I21-I25, I46), 91 from stroke (ICD9 430, 431, 434; ICD10 I60-I60, I61, I63), and 96 from other diseases of circulatory system (ICD9 390-459; ICD10 I00-I99). Women had lower morbidity than men over the 6 years preceding stroke deaths (RR for mean annual days=0.33 (95% CI 0.14-0.78). For other causes of CVD mortality, there were no gender differences in morbidity rates prior to death. In men, those who died from CVD had substantially greater morbidity levels than matched controls through the entire 6-year period preceding death (rate ratio=3.59; 95% confidence interval 2.62-4.93). Among women, morbidity days were greater particularly in the year preceding death from stroke.
Conclusion
Our results on working age men and women suggest no gender differences in morbidity prior to death from heart disease and lower morbidity in women prior to death from stroke. These findings challenge the widespread belief that women experience more morbidity symptoms than men.
doi:10.1016/j.atherosclerosis.2010.04.013
PMCID: PMC3249378  PMID: 20444450
cardiovascular disease; stroke; mortality; gender
21.  Trends in the association between height and socioeconomic indicators in France, 1970–2003 
Economics and human biology  2010;8(3):396-404.
Average physical stature has increased dramatically during the 20th century in many populations across the world with few exceptions. It remains unclear if social inequalities in height persist despite improvements in living standards in the welfare economies of Western Europe. We examined trends in the association between height and socioeconomic indicators in adults over three decades in France. The data were drawn from the French Decennial Health Surveys: a multistage, stratified, random survey of households, representative of the population, conducted in 1970, 1980, 1991, and 2003. We categorised age into 10-year bands, 25–34, 35–44, 45–54 and 55–64 years. Education and income were the two socioeconomic measures used. The slope index of inequality (SII) was used as a summary index of absolute social inequalities in height. The results show that average height increased over this period; men and women aged 25–34 years were 171.9 and 161.2 cm tall in 1970 and 177.0 and 164.0 cm in 2003. However, education-related inequalities in height remained unchanged over this period and in men were 4.48 cm (1970), 4.71 cm (1980), 5.58 cm (1991) and 4.69 cm (2003), the corresponding figures in women were 2.41, 2.37, 3.14 and 2.96 cm. Income-related inequalities in height were smaller and much attenuated after adjustment for education. These results suggest that in France, social inequalities in adult height in absolute terms have remained unchanged across the three decades under examination.
doi:10.1016/j.ehb.2010.03.002
PMCID: PMC2914812  PMID: 20400383
height; trends; social inequalities
22.  Effects of depressive symptoms and coronary heart disease and their interactive associations on mortality in middle-aged adults: the Whitehall II cohort study 
Heart  2010;96(20):1645-1650.
BACKGROUND
Depression and mortality have been studied separately in patients with coronary heart disease (CHD) and in populations healthy at study inception. This does not allow comparisons across risk-factor groups based on the cross-classification of depression and CHD status.
OBJECTIVE
To examine effects of depressive symptoms and coronary heart disease and their interactive associations on mortality in middle-aged adults followed over 5.6 years.
DESIGN AND SETTING
A prospective population-based cohort study of 5936 middle-aged men and women from the British Whitehall II study. We created 4 risk-factor-groups based on the cross classification of depressive symptoms and CHD status.
RESULTS
The age- and sex-adjusted hazard ratios for death from all causes were 1.67 (p<0.05) for participants with only CHD, 2.10 (p<0.001) for those with only depressive symptoms and 4.99 (p<0.001) for those with both CHD and depressive symptoms when compared to participants without either condition. The two latter risk-factor groups remained at increased risk after adjustments for relevant confounders. The relative excess risk due to the interaction between depressive symptoms and CHD for all-cause mortality was 3.58 (95% CI, −0.09–7.26), showing some evidence of an additive interaction. A similar pattern was also observed for cardiovascular death.
CONCLUSIONS
This study provides evidence that depressive symptoms are associated with an increased risk of all-cause and cardiovascular death and that this risk is particularly marked in depressive participants with co-morbid CHD.
doi:10.1136/hrt.2010.198507
PMCID: PMC3151258  PMID: 20844294
Coronary heart disease; depressive symptoms; survival
23.  Does depression predict coronary heart disease and cerebrovascular disease equally well? The Health and Social Support Prospective Cohort Study 
Background The relationship between depression and cerebrovascular disease (CBVD) continues to be debated although little research has compared the predictive power of depression for coronary heart disease (CHD) with that for CBVD within the same population. This study aimed to compare the importance of depression for CHD and CBVD within the same population of adults free of apparent cardiovascular disease.
Methods A random sample of 23 282 adults (9507 men, 13 775 women) aged 20–54 years were followed up for 7 years. Fatal and first non-fatal CHD and CBVD events were documented by linkage to the National-hospital-discharge and mortality registers.
Results Sex–age–education-adjusted hazard ratio (HR) for CHD was 1.66 [95% confidence interval (CI) 1.24–2.24] for participants with mild to severe depressive symptoms, i.e. those scoring ≥10 on the 21-item Beck Depression Inventory, and 2.04 (1.27–3.27) for those who filled antidepressant prescriptions compared with those without depression markers in 1998, i.e. at study baseline. For CBVD, the corresponding HRs were 1.01 (0.67–1.53) and 1.77 (0.95–3.29). After adjustment for behavioural and biological risk factors these associations were reduced but remained evident for CHD, the adjusted HRs being 1.47 (1.08–1.99) and 1.72 (1.06–2.77). For CBVD, the corresponding multivariable adjusted HRs were 0.87 (0.57–1.32) and 1.52 (0.81–2.84).
Conclusions Self-reported depression using a standardized questionnaire and clinical markers of mild to severe depression were associated with an increased risk for CHD. There was no clear evidence that depression is a risk factor for CBVD, but this needs further confirmation.
doi:10.1093/ije/dyq050
PMCID: PMC2950797  PMID: 20360321
Depression; coronary heart disease; cerebrovascular disease
24.  Does depression predict coronary heart disease and cerebrovascular disease equally well? The Health and Social Support Prospective Cohort Study 
Background
The relationship between depression and cerebrovascular disease (CBVD) continues to be debated although little research has compared the predictive power of depression for coronary heart disease (CHD) to that for CBVD within the same population. This study aimed to compare the importance of depression for CHD and CBVD within the same population of adults free of apparent cardiovascular disease.
Methods
A random sample of 23282 adults (9507 men, 13775 women) aged 20–54 years were followed-up for 7 years. Fatal and first non-fatal CHD and CBVD events were documented by linkage to the National-hospital-discharge and mortality registers.
Results
Sex-age-education-adjusted Hazard Ratio (HR) for CHD was 1.66 (95% confidence interval (CI) 1.24–2.24) for participants with mild to severe depressive symptoms, i.e. those scoring 10 or more on the 21-item Beck-Depression-Inventory, and 2.04 (1.27–3.27) for those who filled antidepressant prescriptions compared to those without depression markers in 1998, i.e., at study baseline. For CBVD, the corresponding HRs were 1.01 (0.67–1.53) and 1.77 (0.95–3.29). After adjustment for behavioural and biological risk factors these associations were reduced but remained evident for CHD, the adjusted HRs being 1.47 (1.08–1.99) and 1.72 (1.06–2.77). For CBVD, the corresponding multivariable adjusted HRs were 0.87 (0.57–1.32) and 1.52 (0.81–2.84).
Conclusions
Self-reported depression using a standardized questionnaire and clinical markers of mild to severe depression were associated with an increased risk for CHD. There was no clear evidence that depression is a risk factor for CBVD, but this needs further confirmation.
doi:10.1093/ije/dyq050
PMCID: PMC2950797  PMID: 20360321
Adult; Coronary Disease; epidemiology; psychology; Depression; complications; Female; Finland; epidemiology; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; epidemiology; psychology; Young Adult; depression; coronary heart disease; cerebrovascular disease
25.  Predictive utility of the Framingham general cardiovascular disease risk profile for cognitive function: evidence from the Whitehall II study 
European Heart Journal  2011;32(18):2326-2332.
Aims
Vascular risk factors are associated with cognitive impairment and dementia, although most of the research in this domain focuses on cerebrovascular factors. We examined the relationship between the recently developed Framingham general cardiovascular risk profile and cognitive function and 10-year decline in late midlife.
Methods and results
Study sample comprised of 3486 men and 1341 women, mean age 55 years [standard deviation (SD)=6], from the Whitehall II study, a longitudinal British cohort study. The Framingham General Cardiovascular Risk profile, assessed between 1997 and 1999, included age, sex, HDL cholesterol, total cholesterol, systolic blood pressure, smoking status, and diabetes status. Measures of cognitive function consisted of tests of reasoning (Alice Heim 4-I), memory, phonemic and semantic fluency, and vocabulary (Mill-Hill), assessed three times (1997–1999, 2002–2004, 2007–2009) over 10 years. In cross-sectional age-adjusted models, 10% point increments in cardiovascular risk were associated with poor performance in all cognitive domains in both men and women (all P-values <0.001). In models adjusted for age, ethnicity, marital status, and education, 10% higher cardiovascular risk was associated with greater overall 10-year cognitive decline in men, reasoning in particular (−0.47; 95% CI: −0.81, −0.11).
Conclusion
In middle-aged individuals free of cardiovascular disease, an adverse cardiovascular risk profile is associated with poor cognitive function, and decline in at least one cognitive domain in men.
doi:10.1093/eurheartj/ehr133
PMCID: PMC3172575  PMID: 21606085
Framingham General Cardiovascular Profile; Cognitive function; Cardiovascular risk scores; Cognitive decline

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