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1.  Monocyte cytokine synthesis in response to extracellular cell stress proteins suggests these proteins exhibit network behaviour 
Cell Stress & Chaperones  2013;19(1):135-144.
Human peripheral blood monocytes were exposed to single or pairs of cell stress proteins (CSPs), specifically Hsp10, Hsp27, Hsp60 and Hsp70—the former two having anti-inflammatory actions while the latter pair being assumed to be pro-inflammatory in activity. This study was to test if these proteins exhibited any network behaviour. To control for possible lipopolysaccharide contamination, polymyxin B was used. Surprisingly, at concentrations higher than 1 μg/ml, polymyxin B itself could induce cytokine synthesis. A number of commercial sources of the molecular chaperones were tested, and marked variations in monocyte cytokine synthesis were found. All four CSPs stimulated the same profile of IL-1/IL-6 synthesis and IL-10/TNF-α synthesis although the kinetics of production of these two pairs of cytokines were very different. A key question was whether extracellular molecular chaperones exhibited network behaviour. To test this, monocytes were cultured with suboptimal concentrations of single CSP and pairs of CSP to look for additive, synergistic or antagonistic cell responses. The major finding was that pairs of molecular chaperones, including chaperones thought to stimulate monocyte cytokine synthesis, could produce significant antagonistic cellular responses. This demonstrates that extracellular CSPs constitute an additional potent layer within the complex cytokine network and furthermore suggests that monocytes have evolved to dampen their immune responses upon exposure to extracellular networks of CSPs—perhaps as a mechanism for protecting cells against detrimental cellular stress responses.
PMCID: PMC3857429  PMID: 23775284
Cell stress proteins; Cytokines; Network behaviour; Inflammation
2.  Identifying hopelessness in population research: a validation study of two brief measures of hopelessness 
BMJ Open  2014;4(5):e005093.
Hopelessness is an important construct in psychosocial epidemiology, but there is great pressure on the length of questionnaire measures in large-scale population and clinical studies. We examined the validity and test–retest reliability of two brief measures of hopelessness, an existing negatively worded two-item measure of hopelessness (Brief-H-Neg) and a positively worded version of the same instrument (Brief-H-Pos).
Cohort study.
Control arm of the UK Collaborative Trial of Ovarian Cancer Screening.
A non-clinical research-based sample of 5000 postmenopausal women selected from 56 512 participants.
Primary and secondary outcome measures
Spearman's rank correlation of brief measures of hopelessness with the Beck Hopelessness Scale (BHS). Spearman's rank correlation with the Centre for Epidemiological Studies Depression Scale (CES-D) and change in mean score on repeat testing.
Two short hopelessness measures, a negatively worded brief measure of hopelessness (Brief-H-Neg) and a positively worded brief measure of hopelessness (Brief-H-Pos), were administered by postal questionnaire to 5000 women together with the 20-item BHS and 20-item CES-D. The Brief-H-Neg and Brief-H-Pos were readministered to 500 women after a 2-week interval.
2413 postmenopausal women (mean age 68.9 years) completed the questionnaire. The Brief-H-Neg and Brief-H-Pos correlated 0.93 and 0.87 with the BHS after correction for attenuation and their association with the CES-D mirrored that seen with the BHS (Spearman's rank correlation 0.88 and 0.68, respectively). There was no change in mean scores on the two measures with repeat testing in the 433 women who completed them and test–retest reliability was good (intraclass correlations Brief-H-Neg 0.67 and Brief-H-Pos 0.72).
These findings provide support for the validity of the Brief-H-Neg and Brief-H-Pos. These brief measures are likely to be useful in large population studies assessing hopelessness.
Trial registration number
PMCID: PMC4039863  PMID: 24879829
Epidemiology; Mental Health
3.  Intentional and unintentional non-adherence to medications following an acute coronary syndrome: A longitudinal study 
Journal of Psychosomatic Research  2014;76(5):430-432.
Non-adherence to medication is common among coronary heart disease patients. Non-adherence to medication may be either intentional or unintentional. In this analysis we provide estimates of intentional and unintentional non-adherence in the year following an acute coronary syndrome (ACS).
In this descriptive prospective observational study of patients with confirmed ACS medication adherence measures were derived from responses to the Medication Adherence Report Scale at approximately 2 weeks (n = 223), 6 months (n = 139) and 12 months (n = 136) following discharge from acute treatment for ACS.
Total medication non-adherence was 20%, 54% and 53% at each of these time points respectively. The corresponding figures for intentional non-adherence were 8%, 15% and 15% and 15%, 52% and 53% for unintentional non-adherence. There were significant increases in the levels of medication non-adherence between the immediate discharge period (2 weeks) and 6 months that appeared to stabilize between 6 and 12 months after acute treatment for ACS.
Unintentional non-adherence to medications may be the primary form of non-adherence in the year following ACS. Interventions delivered early in the post-discharge period may prevent the relatively high levels of non-adherence that appear to become established by 6 months following an ACS.
PMCID: PMC4005033  PMID: 24745787
Adherence; Acute coronary syndrome; Psychological; Intention
4.  The relationship between cortisol responses to laboratory stress and cortisol profiles in daily life 
Biological Psychology  2014;99(100):34-40.
•Few studies have examined associations between laboratory and everyday cortisol.•Cortisol responses to laboratory stress were associated with cortisol AUCday.•This provides evidence of the ecological validity of laboratory stress testing.
Relationships between cortisol responses to laboratory stress and cortisol output over the day have not been studied extensively. We tested associations between cortisol responses to a set of laboratory challenges (colour/word interference and mirror tracing) and three aspects of cortisol output over the day, namely total area under the curve (AUCday), the cortisol awakening response (CAR) and the slope of cortisol decline over the day. Participants were 466 men and women aged 54–76 years. We found that cortisol responses to laboratory stress were positively associated with cortisol AUCday independently of sex, age, socioeconomic status, smoking, body mass index, and time of laboratory testing (B = 0.212, 95% C.I. 0.143–0.282, p < 0.001). No associations between laboratory responses and the CAR or cortisol slope were observed. The laboratory–field association was not moderated by demographic or psychosocial factors. The study provides evidence for the ecological validity of acute laboratory stress testing.
PMCID: PMC4031630  PMID: 24582772
Stress reactivity; Laboratory–field; HPA axis; Cortisol
5.  Cytomegalovirus is associated with reduced telomerase activity in the Whitehall II cohort 
Experimental gerontology  2013;48(4):385-390.
Telomere length and telomerase activity have received increased attention as markers of cellular aging, but the determinants of inter-individual variation in these markers are incompletely understood. Cytomegalovirus (CMV) infection may be particularly important for telomere and telomerase dynamics due to its dramatic impact on peripheral blood lymphocyte composition, i.e., increasing the number and proportions of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA). However, the possible relationship between CMV infection and leukocyte TL and TA has not been well-examined in vivo. This study examined the associations of CMV seropositivity and CMV IgG antibodies with leukocyte (TL) and (TA) in a sample of 434 healthy individuals (ages 53–76) from the Whitehall II cohort. Positive CMV serostatus was significantly associated with lower TA among women, and higher CMV IgG antibody levels were associated with lower TA in the overall sample. However, neither CMV seropositivity nor CMV IgG antibody levels (reflecting subclinical reactivation) among the seropositive were significantly associated with TL. These associations were robust to adjustment for age, employment grade, BMI, and smoking status. The results demonstrate that CMV seropositivity and subclinical reactivation predict lower TA. Future longitudinal studies should test whether the association of CMV with lower TA contributes to accelerated telomere shortening over time.
PMCID: PMC3626117  PMID: 23403382
telomeres; telomerase; cytomegalovirus; infections; Whitehall II
6.  Enjoyment of life and declining physical function at older ages: a longitudinal cohort study 
Positive affective well-being (i.e., feelings of happiness and enjoyment) has been associated with longer survival and reduced incidence of serious illness. Our objective was to discover whether enjoyment of life also predicted a reduced risk of functional impairment over an 8-year period in a large population sample.
We carried out a prospective analysis involving 3199 men and women aged 60 years or older from the English Longitudinal Study of Ageing. Enjoyment of life was assessed by questionnaire. Outcomes were impairment in 2 or more activities of daily living and changes in gait speed on a walking test. Covariates included sociodemographic factors, baseline health, depressive symptoms, impairment of mobility and health behaviours.
Two or more impaired activities of daily living developed among 4.4%, 11.7% and 16.8% of participants in the high, medium and low enjoyment-of-life tertiles, respectively. After adjustment for covariates, the odds of impaired activities of daily living developing were 1.83 (95% confidence interval 1.13–2.96) in the low compared with high tertile. Gait speed after 8 years was also related to baseline enjoyment of life after adjustment for gait speed and other covariates at baseline (p < 0.001). We obtained similar results when we limited analyses to participants younger than 70 years at baseline.
This is an observational study, so causal conclusions cannot be drawn. But our results provide evidence that reduced enjoyment of life may be related to the future disability and mobility of older people.
PMCID: PMC3940591  PMID: 24446463
7.  Depression, C-reactive protein and length of post-operative hospital stay in coronary artery bypass graft surgery patients 
Brain, Behavior, and Immunity  2014;37(100):115-121.
•Elevated depression symptoms prior to CABG were associated with increased odds of extended hospital stays and post-operative CRP responses mediated this association.
This study aimed to explore the role of C-reactive protein (CRP) in mediating the association between greater pre-operative depression symptoms and longer post-operative length of stay in patients undergoing coronary artery bypass graft (CABG) surgery. We used a sample of 145 elective CABG patients and measured depression symptoms using the Beck Depression Inventory (BDI) prior to surgery and collected baseline measures of CRP. Participants were followed up during their in-hospital stay to measure early (1–3 days post-surgery) and persistent (4–8 days post-surgery) CRP responses to surgery. We found that compared with participants with low depression symptoms, those with elevated depression symptoms (BDI > 10) prior to CABG were at increased odds of a hospital stay of greater than one week (OR 3.51, 95% CI 1.415–8.693, p = 0.007) and that greater persistent CRP responses mediated this association. Further work is needed to explore the exact physiological pathways through which depression and CRP interact to affect recovery in CABG patients.
PMCID: PMC3969589  PMID: 24239712
Depression; C-reactive protein; Coronary artery bypass grafting; Recovery
8.  The associations between unhealthy behaviours, mental stress, and low socio-economic status in an international comparison of representative samples from Thailand and England 
Socioeconomic status is a recognised determinant of health status, and the association may be mediated by unhealthy behaviours and psychosocial adversities, which, in developed countries, both aggregate in low socioeconomic sectors of the population. We explored the hypothesis that unhealthy behavioural choices and psychological distress do not both aggregate in low socioeconomic status groups in developing countries.
Our study is based on a cross-sectional comparison between national population samples of adults in England and Thailand. Psychological distress was assessed using the General Health Questionnaire (GHQ-12) or three anxiety-oriented items from the Kessler scale (K6). Socioeconomic status was assessed on the basis of occupational status. We computed a health-behaviour score using information about smoking, alcohol consumption, fruit and vegetable consumption, and physical activity.
The final sample comprised 40,679 participants. In both countries and in both genders separately, there was a positive association between poor health-behaviour and high psychological distress, and between high psychological distress and low socioeconomic status. In contrast, the association between low socioeconomic status and poor health-behaviour was positive in both English men and women, flat in Thai men, and was negative in Thai women (likelihood ratio test P <0.001).
The associations between socioeconomic status, behavioural choices, and psychological distress are different at the international level. Psychological distress may be consistently associated with low socioeconomic status, whereas poor health-behaviour is not. Future analyses will test whether psychological distress is a more consistent determinant of socioeconomic differences in health across countries.
PMCID: PMC3933467  PMID: 24555674
Psychological stress; Psychosocial deprivation; Health behavior; Social class
9.  The combined association of depression and socioeconomic status with length of post-operative hospital stay following coronary artery bypass graft surgery: Data from a prospective cohort study☆ 
To understand the association between pre-operative depression symptoms, including cognitive and somatic symptom subtypes, and length of post-operative stay in patients undergoing coronary artery bypass graft (CABG) surgery, and the role of socioeconomic status (SES).
We measured depression symptoms using the Beck Depression Inventory (BDI) and household income in the month prior to surgery in 310 participants undergoing elective, first-time, CABG. Participants were followed-up post-operatively to assess the length of their hospital stay.
We showed that greater pre-operative depression symptoms on the BDI were associated with a longer hospital stay (hazard ratio = 0.978, 95% CI 0.957–0.999, p = .043) even after controlling for covariates, with the effect being observed for cognitive symptoms of depression but not somatic symptoms. Lower SES augmented the negative effect of depression on length of stay.
Depression symptoms interact with socioeconomic position to affect recovery following cardiac surgery and further work is needed in order to understand the pathways of this association.
PMCID: PMC3991423  PMID: 24360139
ACS, acute coronary syndrome; ARCS study, Adjustment and Recovery after Cardiac Surgery study; BDI, Beck Depression Inventory; BMI, body mass index; CABG, coronary artery bypass graft; CI, confidence intervals; EuroSCORE, European System for Cardiac Operative Risk Evaluation; HADS, Hospital Anxiety and Depression Scale; Depression; Coronary artery bypass graft surgery; Recovery; Length of stay; Income; Socioeconomic position
10.  The Association Between Cortisol Response to Mental Stress and High-Sensitivity Cardiac Troponin T Plasma Concentration in Healthy Adults 
The objective of this study was to examine the association between cortisol response to mental stress and high-sensitivity cardiac troponin T (hs-cTnT) in healthy older individuals without history of cardiovascular disease (CVD).
Mental stress is a recognized risk factor for CVD, although the mechanisms remain unclear. Cortisol, a key stress hormone, is associated with coronary atherosclerosis and may accentuate structural and functional cardiac disease.
This cross-sectional study involved 508 disease-free men and women aged 53 to 76 years drawn from the Whitehall II epidemiological cohort. We evaluated salivary cortisol response to standardized mental stress tests (exposure) and hs-cTnT plasma concentration using a high-sensitivity assay (outcome). We measured coronary calcification using electron-beam dual-source computed tomography and Agatston scores.
After adjustment for demographic and clinical variables associated with CVD as well as for inflammatory factors, we found a robust association between cortisol response and detectable hs-cTnT (odds ratio [OR]: 3.98; 95% confidence interval [CI]: 1.60 to 9.92; p = 0.003). The association remained when we restricted the analysis to participants without coronary calcification (n = 222; OR: 4.77; 95% CI: 1.22 to 18.72; p = 0.025) or when we further adjusted for coronary calcification in participants with positive Agatston scores (n = 286; OR: 7.39; 95% CI: 2.22 to 26.24; p = 0.001).
We found that heightened cortisol response to mental stress was associated with detectable plasma levels of cTnT using high-sensitivity assays in healthy participants, independently of coronary atherosclerosis. Further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage.
PMCID: PMC3807660  PMID: 23810896
atherosclerotic plaque; computed tomography; myocardial infarction; psychological stress; troponin T; AMI, acute myocardial infarction; BMI, body mass index; CAC, coronary artery calcification; CRP, C-reactive protein; CVD, cardiovascular disease; hs-cTnT, high-sensitivity cardiac troponin T; IL, interleukin; HDL, high-density lipoprotein; LDL, low-density lipoprotein
11.  Objectively assessed sedentary time and type 2 diabetes mellitus: a case–control study 
Diabetologia  2013;56:2761-2762.
PMCID: PMC3825498  PMID: 24078056
Accelerometry; Case–control; Physical activity; Sedentary; Type 2 diabetes mellitus
12.  Perceived age discrimination in older adults 
Age and Ageing  2013;43(3):379-386.
Objectives: to examine perceived age discrimination in a large representative sample of older adults in England.
Methods: this cross-sectional study of over 7,500 individuals used data from the fifth wave of the English Longitudinal Study of Ageing (ELSA), a longitudinal cohort study of men and women aged 52 years and older in England. Wave 5 asked respondents about the frequency of five everyday discriminatory situations. Participants who attributed any experiences of discrimination to their age were treated as cases of perceived age discrimination. Multivariable logistic regression analysis was used to estimate the odds ratios of experiencing perceived age discrimination in relation to selected sociodemographic factors.
Results: approximately a third (33.3%) of all respondents experienced age discrimination, rising to 36.8% in those aged 65 and over. Perceived age discrimination was associated with older age, higher education, lower levels of household wealth and being retired or not in employment. The correlates of age discrimination across the five discriminatory situations were similar.
Conclusion: understanding age discrimination is vital if we are to develop appropriate policies and to target future interventions effectively. These findings highlight the scale of the challenge of age discrimination for older adults in England and illustrate that those groups are particularly vulnerable to this form of discrimination.
PMCID: PMC4081784  PMID: 24077751
discrimination; ageing; ageism; ELSA; England; older adults
13.  Job Strain and Cardiovascular Disease Risk Factors: Meta-Analysis of Individual-Participant Data from 47,000 Men and Women 
PLoS ONE  2013;8(6):e67323.
Job strain is associated with an increased coronary heart disease risk, but few large-scale studies have examined the relationship of this psychosocial characteristic with the biological risk factors that potentially mediate the job strain – heart disease association.
Methodology and Principal Findings
We pooled cross-sectional, individual-level data from eight studies comprising 47,045 participants to investigate the association between job strain and the following cardiovascular disease risk factors: diabetes, blood pressure, pulse pressure, lipid fractions, smoking, alcohol consumption, physical inactivity, obesity, and overall cardiovascular disease risk as indexed by the Framingham Risk Score. In age-, sex-, and socioeconomic status-adjusted analyses, compared to those without job strain, people with job strain were more likely to have diabetes (odds ratio 1.29; 95% CI: 1.11–1.51), to smoke (1.14; 1.08–1.20), to be physically inactive (1.34; 1.26–1.41), and to be obese (1.12; 1.04–1.20). The association between job strain and elevated Framingham risk score (1.13; 1.03–1.25) was attributable to the higher prevalence of diabetes, smoking and physical inactivity among those reporting job strain.
In this meta-analysis of work-related stress and cardiovascular disease risk factors, job strain was linked to adverse lifestyle and diabetes. No association was observed between job strain, clinic blood pressure or blood lipids.
PMCID: PMC3688665  PMID: 23840664
14.  Associations of job strain and lifestyle risk factors with risk of coronary artery disease: a meta-analysis of individual participant data 
It is unclear whether a healthy lifestyle mitigates the adverse effects of job strain on coronary artery disease. We examined the associations of job strain and lifestyle risk factors with the risk of coronary artery disease.
We pooled individual-level data from 7 cohort studies comprising 102 128 men and women who were free of existing coronary artery disease at baseline (1985–2000). Questionnaires were used to measure job strain (yes v. no) and 4 lifestyle risk factors: current smoking, physical inactivity, heavy drinking and obesity. We grouped participants into 3 lifestyle categories: healthy (no lifestyle risk factors), moderately unhealthy (1 risk factor) and unhealthy (2–4 risk factors). The primary outcome was incident coronary artery disease (defined as first nonfatal myocardial infarction or cardiac-related death).
There were 1086 incident events in 743 948 person-years at risk during a mean follow-up of 7.3 years. The risk of coronary artery disease among people who had an unhealthy lifestyle compared with those who had a healthy lifestyle (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.18–2.98; population attributable risk 26.4%) was higher than the risk among participants who had job strain compared with those who had no job strain (HR 1.25, 95% CI 1.06–1.47; population attributable risk 3.8%). The 10-year incidence of coronary artery disease among participants with job strain and a healthy lifestyle (14.7 per 1000) was 53% lower than the incidence among those with job strain and an unhealthy lifestyle (31.2 per 1000).
The risk of coronary artery disease was highest among participants who reported job strain and an unhealthy lifestyle; those with job strain and a healthy lifestyle had half the rate of disease. A healthy lifestyle may substantially reduce disease risk among people with job strain.
PMCID: PMC3680555  PMID: 23670152
15.  Influences of early shift work on the diurnal cortisol rhythm, mood and sleep: Within-subject variation in male airline pilots 
Psychoneuroendocrinology  2013;38(4):533-541.
We aimed to investigate how early and late work shifts influenced the diurnal cortisol rhythm using a within-subjects study design. Participants were 30 healthy male non-smoking pilots, mean age 39.4, employed by a short-haul airline. The standard rotating shift pattern consisted of 5 early shifts (starting before 0600 h), followed by 3 rest days, 5 late shifts (starting after 1200 h) and 4 rest days. Pilots sampled saliva and completed subjective mood ratings in a logbook 6 times over the day on two consecutive early shift days, two late days and two rest days. Sampling was scheduled at waking, waking + 30 m, waking + 2.5 h, waking + 8 h, waking + 12 h and bedtime. Waking time, sleep duration, sleep quality and working hours were also recorded. Cortisol responses were analysed with repeated measures analysis of variance with shift condition (early, late, rest) and sample time (1–6) as within-subject factors. Early shifts were associated with a higher cortisol increase in response to awakening (CARi), a greater total cortisol output over the day (AUCG) and a slower rate of decline over the day than late shifts or rest days. Early shifts were also associated with shorter sleep duration but co-varying for sleep duration did not alter the effects of shift on the cortisol rhythm. Both types of work shift were associated with more stress, tiredness and lower happiness than rest days, but statistical adjustment for mood ratings did not alter the findings. Early shift days were associated with significantly higher levels of circulating cortisol during waking hours than late shifts or rest days.
PMCID: PMC3608033  PMID: 22877997
Shift work; Cortisol; Hpa axis; Time of waking; Sleep
16.  Body Mass Index, Muscle Strength and Physical Performance in Older Adults from Eight Cohort Studies: The HALCyon Programme 
PLoS ONE  2013;8(2):e56483.
To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies.
Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI.
Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.
PMCID: PMC3577921  PMID: 23437142
17.  Characteristics of people with low health literacy on coronary heart disease GP registers in South London: a cross-sectional study 
BMJ Open  2013;3(1):e001503.
To explore characteristics associated with, and prevalence of, low health literacy in patients recruited to investigate the role of depression in patients on General Practice (GP) Coronary Heart Disease (CHD) registers (the Up-Beat UK study).
Cross-sectional cohort. The health literacy measure was the Rapid Estimate of Health Literacy in Medicine (REALM). Univariable analyses identified characteristics associated with low health literacy and compared health service use between health literacy statuses. Those variables where there was a statistically significant/borderline significant difference between health literacy statuses were entered into a multivariable model.
16 General Practices in South London, UK.
Inclusion: patients >18 years, registered with a GP and on a GP CHD register. Exclusion: patients temporarily registered.
Primary outcome measure
Of the 803 Up-Beat cohort participants, 687 (85.55%) completed the REALM of whom 106 (15.43%) had low health literacy. Twenty-eight participants could not be included in the multivariable analysis due to missing predictor variable data, leaving a sample of 659. The variables remaining in the final model were age, gender, ethnicity, Indices of Multiple Deprivation score, years of education, employment; body mass index and alcohol intake, and anxiety scores (Hospital Anxiety and Depression Scale). Univariable analysis also showed that people with low health literacy may have more, and longer, practice nurse consultations than people with adequate health literacy.
There is a disadvantaged group of people on GP CHD registers with low health literacy. The multivariable model showed that patients with low health literacy have significantly higher anxiety levels than people with adequate health literacy. In addition, the univariable analyses show that such patients have more, and longer, consultations with practice nurses. We will collect 4-year longitudinal cohort data to explore the impact of health literacy in people on GP CHD registers and the impact of health literacy on health service use.
PMCID: PMC3549254  PMID: 23293243
Health literacy; Cardiovascular disease; Prevalence
18.  Longitudinal patterns in physical activity and sedentary behaviour from mid-life to early old age: a substudy of the Whitehall II cohort 
There are few longitudinal data on physical activity patterns from mid-life into older age. The authors examined associations of self-reported physical activity, adiposity and socio-demographic factors in mid-life with objectively assessed measures of activity in older age.
Participants were 394 healthy men and women drawn from the Whitehall II population-based cohort study. At the baseline assessment in 1997 (mean age 54 years), physical activity was assessed through self-report and quantified as metabolic equivalent of task hours/week. At the follow-up in 2010 (mean age 66 years), physical activity was objectively measured using accelerometers worn during waking hours for seven consecutive days (average daily wear time 891±68 min/day).
Self-reported physical activity at baseline was associated with objectively assessed activity at follow-up in various activity categories, including light-, moderate- and vigorous-intensity activity (all ps<0.04). Participants in the highest compared with lowest quartile of self-reported activity level at baseline recorded on average 64.1 (95% CI 26.2 to 102.1) counts per minute more accelerometer-assessed activity at follow-up and 9.0 (2.0–16.0) min/day more moderate-to-vigorous daily activity, after adjusting for baseline covariates. Lower education, obesity and self-perceived health status were also related to physical activity at follow-up. Only age and education were associated with objectively measured sedentary time at follow-up.
Physical activity behaviour in middle age was associated with objectively measured physical activity in later life after 13 years of follow-up, suggesting that the habits in adulthood are partly tracked into older age.
PMCID: PMC3505863  PMID: 22791800
Actigraph; ageing; education; epidemiology; obesity; physical activity; health behaviour; psychological stress; prevention; coronary heart disease
19.  Short Sleep Duration Is Associated with Shorter Telomere Length in Healthy Men: Findings from the Whitehall II Cohort Study 
PLoS ONE  2012;7(10):e47292.
Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people.
Participants were 434 men and women aged 63.3 years on average drawn from the Whitehall II cohort study. Sleep duration was measured by self-report.
There was a linear association between sleep duration and leukocyte telomere length in men but not in women (P = 0.035). Men reporting shorter sleep duration had shorter telomeres, independently of age, body mass index, smoking, educational attainment, current employment, cynical hostility scores and depressive symptoms. Telomeres were on average 6% shorter in men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per night.
This study adds to the growing literature relating sleep duration with biomarkers of aging, and suggests that shortening of telomeres might reflect mechanisms through which short sleep contributes to pathological conditions in older men.
PMCID: PMC3483149  PMID: 23144701
20.  Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data 
Lancet  2012;380(9852):1491-1497.
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.
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.
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%.
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.
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.
PMCID: PMC3486012  PMID: 22981903
21.  Job Strain and Tobacco Smoking: An Individual-Participant Data Meta-Analysis of 166 130 Adults in 15 European Studies 
PLoS ONE  2012;7(7):e35463.
Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults.
Methodology and Principal Findings
We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking.
Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.
PMCID: PMC3391192  PMID: 22792154
22.  Job Strain and Alcohol Intake: A Collaborative Meta-Analysis of Individual-Participant Data from 140 000 Men and Women 
PLoS ONE  2012;7(7):e40101.
The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake.
Methodology and Principal Findings
We analysed cross-sectional data from 12 European studies (n = 142 140) and longitudinal data from four studies (n = 48 646). Job strain and alcohol intake were self-reported. Job strain was analysed as a binary variable (strain vs. no strain). Alcohol intake was harmonised into the following categories: none, moderate (women: 1–14, men: 1–21 drinks/week), intermediate (women: 15–20, men: 22–27 drinks/week) and heavy (women: >20, men: >27 drinks/week). Cross-sectional associations were modelled using logistic regression and the results pooled in random effects meta-analyses. Longitudinal associations were examined using mixed effects logistic and modified Poisson regression. Compared to moderate drinkers, non-drinkers and (random effects odds ratio (OR): 1.10, 95% CI: 1.05, 1.14) and heavy drinkers (OR: 1.12, 95% CI: 1.00, 1.26) had higher odds of job strain. Intermediate drinkers, on the other hand, had lower odds of job strain (OR: 0.92, 95% CI: 0.86, 0.99). We found no clear evidence for longitudinal associations between job strain and alcohol intake.
Our findings suggest that compared to moderate drinkers, non-drinkers and heavy drinkers are more likely and intermediate drinkers less likely to report work-related stress.
PMCID: PMC3391232  PMID: 22792218
23.  Hostility and Cellular Aging in Men from the Whitehall II Cohort 
Biological Psychiatry  2012;71(9):767-773.
Hostility is associated with a significantly increased risk of age-related disease and mortality, yet the pathophysiological mechanisms involved remain unclear. Here we investigated the hypothesis that hostility might impact health by promoting cellular aging.
We tested the relationship between cynical hostility and two known markers of cellular aging, leukocyte telomere length (TL) and leukocyte telomerase activity (TA), in 434 men and women from the Whitehall II cohort.
High-hostile men had significantly shorter leukocyte TL than their low-hostile counterparts. They also had elevated leukocyte TA, with a significantly increased likelihood of having both short TL and high TA, compared with low-hostile individuals.
Because telomerase is known to counteract telomere shortening by synthesizing telomeric DNA repeats, particularly in the context of shortened telomeres, heightened TA might represent a compensatory response in high-hostile individuals. The relationship between hostility and disease is stronger in men than in women, and men generally have a shorter life expectancy than women. Our findings suggest that telomere attrition might represent a novel mechanism mediating the detrimental effects of hostility on men's health.
PMCID: PMC3657139  PMID: 21974787
Aging; gender; hostility; psychological stress; telomerase activity; telomere length
24.  Psychosocial biomarker research: integrating social, emotional and economic factors into population studies of aging and health 
There are complex reciprocal relationships between health and social, emotional and economic factors in aging populations. Social and affective neurosciences are rapidly developing an understanding of the mechanisms underlying these phenomena using sophisticated behavioural, neuroimaging and psychophysiological methods. These techniques are often complex and expensive, so are generally used in relatively small selected samples rather than in large-scale cohort studies. However, an understanding of the significance of these processes in health and well-being depends on integrating findings from social and affective neuroscience into population-level studies. The aim of this article is to describe how a population perspective on the determinants of health and well-being in old age articulates with the agenda of social, affective and economic neuroscience, particularly through the application of psychosocial biomarker research. Social and affective neuroscience and epidemiological approaches provide complementary research strategies for understanding the mechanisms linking social, emotional and economic factors with health risk. This will be illustrated primarily from findings from two studies conducted at University College London, the Whitehall II Study and the English Longitudinal Study of Ageing.
PMCID: PMC3073386  PMID: 20360352
aging; psychosocial; well-being; population studies; biomarkers
25.  Cortisol Responses to Mental Stress and the Progression of Coronary Artery Calcification in Healthy Men and Women 
PLoS ONE  2012;7(2):e31356.
Psychosocial stress is a risk factor for coronary heart disease (CHD). The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA) axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC).
Methods and Results
Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD) and CAC progression (odds ratio = 1.27, 95% CI, 1.02–1.60) after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85–1.24). Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen.
Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD.
PMCID: PMC3273460  PMID: 22328931

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