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1.  Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes 
Psychoneuroendocrinology  2015;51:209-218.
Highlights
•Impaired stress responsivity in type 2 diabetes is associated with a lack of mineralocorticoid and glucocorticoid sensitivity.•Corticosteroid sensitivity in type 2 diabetes correlates to HbA1c.•Type 2 diabetes participants showed blunted response to stress in inflammatory cytokines.
Summary
Psychological stress may contribute to type 2 diabetes but mechanisms are still poorly understood. In this study, we examined whether stress responsiveness is associated with glucocorticoid and mineralocorticoid sensitivity in a controlled experimental comparison of people with type 2 diabetes and non-diabetic participants. Thirty-seven diabetes patients and 37 healthy controls underwent psychophysiological stress testing. Glucocorticoid (GR) and mineralocorticoid sensitivity (MR) sensitivity were measured by dexamethasone- and prednisolone-inhibition of lipopolysaccharide (LPS)-induced interleukin (IL) 6 levels, respectively. Blood pressure (BP) and heart rate were monitored continuously, and we periodically assessed salivary cortisol, plasma IL-6 and monocyte chemotactic protein (MCP-1). Following stress, both glucocorticoid and mineralocorticoid sensitivity decreased among healthy controls, but did not change in people with diabetes. There was a main effect of group on dexamethasone (F(1,74) = 6.852, p = 0.013) and prednisolone (F(1,74) = 7.295, p = 0.010) sensitivity following stress at 45 min after tasks. People with diabetes showed blunted stress responsivity in systolic BP, diastolic BP, heart rate, IL-6, MCP-1, and impaired post-stress recovery in heart rate. People with Diabetes had higher cortisol levels as measured by the total amount excreted over the day and increased glucocorticoid sensitivity at baseline. Our study suggests that impaired stress responsivity in type-2 diabetes is in part due to a lack of stress-induced changes in mineralocorticoid and glucocorticoid sensitivity.
doi:10.1016/j.psyneuen.2014.09.023
PMCID: PMC4275581  PMID: 25462894
HPA axis; Corticosteroid sensitivity; Acute stress; Cytokines; Auto-immune diseases; Cardiovascular
2.  Long working hours, socioeconomic status, and the risk of incident type 2 diabetes: a meta-analysis of published and unpublished data from 222 120 individuals 
Summary
Background
Working long hours might have adverse health effects, but whether this is true for all socioeconomic status groups is unclear. In this meta-analysis stratified by socioeconomic status, we investigated the role of long working hours as a risk factor for type 2 diabetes.
Methods
We identified four published studies through a systematic literature search of PubMed and Embase up to April 30, 2014. Study inclusion criteria were English-language publication; prospective design (cohort study); investigation of the effect of working hours or overtime work; incident diabetes as an outcome; and relative risks, odds ratios, or hazard ratios (HRs) with 95% CIs, or sufficient information to calculate these estimates. Additionally, we used unpublished individual-level data from 19 cohort studies from the Individual-Participant-Data Meta-analysis in Working-Populations Consortium and international open-access data archives. Effect estimates from published and unpublished data from 222 120 men and women from the USA, Europe, Japan, and Australia were pooled with random-effects meta-analysis.
Findings
During 1·7 million person-years at risk, 4963 individuals developed diabetes (incidence 29 per 10 000 person-years). The minimally adjusted summary risk ratio for long (≥55 h per week) compared with standard working hours (35–40 h) was 1·07 (95% CI 0·89–1·27, difference in incidence three cases per 10 000 person-years) with significant heterogeneity in study-specific estimates (I2=53%, p=0·0016). In an analysis stratified by socioeconomic status, the association between long working hours and diabetes was evident in the low socioeconomic status group (risk ratio 1·29, 95% CI 1·06–1·57, difference in incidence 13 per 10 000 person-years, I2=0%, p=0·4662), but was null in the high socioeconomic status group (1·00, 95% CI 0·80–1·25, incidence difference zero per 10 000 person-years, I2=15%, p=0·2464). The association in the low socioeconomic status group was robust to adjustment for age, sex, obesity, and physical activity, and remained after exclusion of shift workers.
Interpretation
In this meta-analysis, the link between longer working hours and type 2 diabetes was apparent only in individuals in the low socioeconomic status groups.
Funding
Medical Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), Economic and Social Research Council, US National Institutes of Health, and British Heart Foundation.
doi:10.1016/S2213-8587(14)70178-0
PMCID: PMC4286814  PMID: 25262544
3.  The impact of a cancer diagnosis on weight change: findings from prospective, population-based cohorts in the UK and the US 
BMC Cancer  2014;14(1):926.
Background
Obesity is a risk factor for cancer incidence and survival, but data on patterns of weight change in cancer survivors are scarce and few stratify by pre-diagnosis weight status. In two population-based cohorts of older adults, we examined weight change in cancer survivors and cancer-free controls in relation to baseline weight status.
Methods
In the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS), we identified participants diagnosed with cancer who had pre- and post-diagnosis BMI data (ELSA n = 264; HRS n = 2553), and cancer-free controls (ELSA n = 1538; HRS n = 4946). Repeated-measures ANOVAs tested three-way interactions by group (cancer/control), time (pre-/post-diagnosis), and pre-diagnosis weight status (normal-weight/overweight/obese).
Results
Mean BMI change was -0.07 (SD = 2.22) in cancer survivors vs. +0.14 (SD = 1.11) in cancer-free controls in ELSA, and -0.20 (SD = 2.84) vs. +0.11 (SD = 0.93) respectively in HRS. Three-way interactions were significant in both cohorts (ELSA p = .015; HRS p < .001). In ELSA, mean BMI change in normal-weight cancer survivors was +0.19 (SD = 1.53) compared with -0.33 (SD = 3.04) in obese survivors. In ELSA controls, the respective figures were +0.09 (SD = 0.81) and +0.16 (SD = 1.50). In HRS, mean change in normal-weight cancer survivors was +0.07 (SD = 2.30) compared with -0.72 (SD = 3.53) in obese survivors. In HRS controls, the respective figures were +0.003 (SD = 0.66) and +0.27 (SD = 1.27).
Conclusion
Over a four-year period, in two cohorts of older adults, cancer survivors lost weight relative to cancer-free controls. However, cancer survivors who were obese pre-diagnosis were more likely to lose weight than healthy-weight survivors or obese adults without a cancer diagnosis. Whether this was due to differences in clinical status or deliberate lifestyle change triggered by the cancer diagnosis is not known. Further research is needed to establish why weight loss occurs more frequently in cancer survivors who were obese at diagnosis, and whether this has favourable effects on mortality.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-926) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-926
PMCID: PMC4265482  PMID: 25487996
Weight loss; Body weight changes; Cancer diagnosis; Overweight; Obese; Cancer survivors
4.  Grip Strength across the Life Course: Normative Data from Twelve British Studies 
PLoS ONE  2014;9(12):e113637.
Introduction
Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol.
Methods
We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing).
Results
Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males’ peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position.
Conclusion
This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.
doi:10.1371/journal.pone.0113637
PMCID: PMC4256164  PMID: 25474696
5.  Cohort Profile: The English Longitudinal Study of Ageing 
The English Longitudinal Study of Ageing (ELSA) is a panel study of a representative cohort of men and women living in England aged ≥50 years. It was designed as a sister study to the Health and Retirement Study in the USA and is multidisciplinary in orientation, involving the collection of economic, social, psychological, cognitive, health, biological and genetic data. The study commenced in 2002, and the sample has been followed up every 2 years. Data are collected using computer-assisted personal interviews and self-completion questionnaires, with additional nurse visits for the assessment of biomarkers every 4 years. The original sample consisted of 11 391 members ranging in age from 50 to 100 years. ELSA is harmonized with ageing studies in other countries to facilitate international comparisons, and is linked to financial and health registry data. The data set is openly available to researchers and analysts soon after collection (http://www.esds.ac.uk/longitudinal/access/elsa/l5050.asp).
doi:10.1093/ije/dys168
PMCID: PMC3900867  PMID: 23143611
Ageing; cohort; longitudinal; UK
6.  Optimism measured pre-operatively is associated with reduced pain intensity and physical symptom reporting after coronary artery bypass graft surgery 
Journal of Psychosomatic Research  2014;77(4):278-282.
Objective
Optimism is thought to be associated with long-term favourable outcomes for patients undergoing coronary artery bypass graft (CABG) surgery. Our objective was to examine the association between optimism and post-operative pain and physical symptoms in CABG patients.
Methods
We assessed optimism pre-operatively in 197 adults undergoing CABG surgery, and then followed them up 6–8 weeks after the procedure to measure affective pain, pain intensity, and physical symptom reporting directly pertaining to CABG surgery.
Results
Greater optimism measured pre-operatively was significantly associated with lower pain intensity (β = − 0.150, CI = − 0.196 to − 0.004, p = .042) and fewer physical symptoms following surgery (β = − 0.287, CI = − 0.537 to − 0.036, p = .025), but not with affective pain, after controlling for demographic, clinical and behavioural covariates, including negative affectivity.
Conclusions
Optimism is a modest, yet significant, predictor of pain intensity and physical symptom reporting after CABG surgery. Having positive expectations may promote better recovery.
Highlights
•Optimism predicts better recovery after coronary artery bypass graft (CABG) surgery.•We found that optimism was associated with lower pain intensity after CABG surgery.•We found that optimism predicted fewer physical symptoms after the CABG procedure.•Having positive expectations may promote better recovery following CABG surgery.
doi:10.1016/j.jpsychores.2014.07.018
PMCID: PMC4188527  PMID: 25129850
Coronary artery bypass graft surgery; Optimism; Pain; Pessimism; Physical symptoms
7.  Psychological Changes following Weight Loss in Overweight and Obese Adults: A Prospective Cohort Study 
PLoS ONE  2014;9(8):e104552.
Background
Participation in weight loss programs is often associated with improved wellbeing alongside reduced cardio-metabolic risk. In contrast, population-based analyses have found no evidence of psychological benefits of weight loss, but this may be due to inclusion of healthy-weight individuals. We therefore examined cardio-metabolic and psychological changes following weight loss in a cohort of overweight/obese adults.
Methods
Data were from 1,979 overweight and obese adults (BMI ≥25 kg/m2; age ≥50 y), free of long-standing illness or clinical depression at baseline, from the English Longitudinal Study of Ageing. Participants were grouped according to four-year weight change into those losing ≥5% weight, those gaining ≥5%, and those whose weight was stable within 5%. Logistic regression examined changes in depressed mood (eight-item Center for Epidemiologic Studies Depression score ≥4), low wellbeing (Satisfaction With Life Scale score <20), hypertension (systolic blood pressure ≥140 mmHg or anti-hypertensives), and high triglycerides (≥1.7 mmol/l), controlling for demographic variables, weight loss intention, and baseline characteristics.
Results
The proportion of participants with depressed mood increased more in the weight loss than weight stable or weight gain groups (+289%, +86%, +62% respectively; odds ratio [OR] for weight loss vs. weight stable = 1.78 [95% CI 1.29–2.47]). The proportion with low wellbeing also increased more in the weight loss group (+31%, +22%, −4%), but the difference was not statistically significant (OR = 1.16 [0.81–1.66]). Hypertension and high triglyceride prevalence decreased in weight losers and increased in weight gainers (−28%, 4%, +18%; OR = 0.61 [0.45–0.83]; −47%, −13%, +5%; OR = 0.41 [0.28–0.60]). All effects persisted in analyses adjusting for illness and life stress during the weight loss period.
Conclusions
Weight loss over four years in initially healthy overweight/obese older adults was associated with reduction in cardio-metabolic risk but no psychological benefit, even when changes in health and life stresses were accounted for. These results highlight the need to investigate the emotional consequences of weight loss.
doi:10.1371/journal.pone.0104552
PMCID: PMC4123950  PMID: 25098417
8.  Linking Stable and Dynamic Features of Positive Affect to Sleep 
Background
Poor sleep contributes to adult morbidity and mortality.
Purpose
The study examined the extent to which trait positive affect (PA) and PA reactivity, defined as the magnitude of change in daily PA in response to daily events, were linked to sleep outcomes.
Methods
Analyses are based on data from 100 respondents selected from the National Survey of Midlife in the United States (MIDUS).
Results
Multilevel analyses indicated that higher levels of trait PA were associated with greater morning rest and better overall sleep quality. In contrast, PA reactivity was associated with diminished sleep efficiency. Finally, interactions between PA reactivity and trait PA emerged on all three sleep measures, such that higher event-related change in daily positive affect was associated with impaired sleep, especially among individuals high in trait PA.
Conclusions
Results suggest that high trait PA, when coupled with high PA reactivity, may contribute to poor sleep.
doi:10.1007/s12160-013-9484-8
PMCID: PMC3709014  PMID: 23483378
trait positive affect; positive affect reactivity; sleep
9.  Attachment anxiety predicts IL-6 and length of hospital stay in coronary artery bypass graft surgery (CABG) patients 
Journal of Psychosomatic Research  2014;77(2):155-157.
Objective
The mechanisms underlying the association between adult attachment and health are not well understood. In the current study, we investigated the relationship between attachment anxiety, attachment avoidance, inflammation, and length of hospital stay in coronary artery bypass graft (CABG) surgery patients.
Method
167 CABG patients completed an attachment questionnaire prior to surgery, and blood samples were taken before and after surgery to assess inflammatory activity.
Results
We found that attachment anxiety predicted higher plasma interleukin 6 (IL-6) concentration, and this association was mediated by self-reported sleep quality. Anxious attachment also predicted longer hospital stays following CABG surgery, even after controlling for demographic and clinical factors.
Conclusion
These data suggest that increased levels of IL-6 may be a process linking adult attachment anxiety with health outcomes.
Highlights
•We examine attachment and inflammation response in 167 CABG patients.•Attachment anxiety predicted higher levels of IL-6 following CABG surgery.•Poor sleep quality mediated this association between attachment anxiety and IL-6.•Attachment anxiety predicted longer hospital stay following CABG surgery.•Increased IL-6 may link attachment anxiety to health outcomes.
doi:10.1016/j.jpsychores.2014.06.002
PMCID: PMC4121675  PMID: 25077858
CABG; Attachment; IL-6; Sleep; Hospital stay
10.  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.
doi:10.1007/s12192-013-0440-0
PMCID: PMC3857429  PMID: 23775284
Cell stress proteins; Cytokines; Network behaviour; Inflammation
11.  Objectively assessed physical activity, adiposity, and inflammatory markers in people with type 2 diabetes 
Objective
Inflammatory processes may play an important role in the development of acute coronary syndromes in people with type 2 diabetes; thus, strategies to control inflammation are of clinical importance. We examined the cross-sectional association between objectively assessed physical activity and inflammatory markers in a sample of people with type 2 diabetes.
Methods
Participants were 71 men and 41 women (mean age=63.9±7 years), without a history of cardiovascular disease, drawn from primary care clinics. Physical activity was objectively measured using waist-worn accelerometers (Actigraph GT3X) during waking hours for seven consecutive days.
Results
We observed inverse associations between moderate-to-vigorous physical activity (per 10 min) with plasma interleukin-6 (B=−0.035, 95% CI −0.056 to −0.015), interleukin-1ra (B=−0.033, 95% CI −0.051 to −0.015), and monocyte chemotactic protein-1 (B=−0.011, 95% CI −0.021 to 0.000). These associations largely persisted in multivariable adjusted models, although body mass index considerably attenuated the effect estimate.
Conclusions
These data demonstrate an inverse association between physical activity and inflammatory markers in people with type 2 diabetes.
doi:10.1136/bmjdrc-2014-000030
PMCID: PMC4212571  PMID: 25452870
Cytokine(s); Epidemiology; Type 2 Diabetes; Physical Activity and Health
12.  Identifying hopelessness in population research: a validation study of two brief measures of hopelessness 
BMJ Open  2014;4(5):e005093.
Objective
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).
Design
Cohort study.
Setting
Control arm of the UK Collaborative Trial of Ovarian Cancer Screening.
Participants
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.
Methods
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.
Results
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).
Conclusions
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
NCT00058032.
doi:10.1136/bmjopen-2014-005093
PMCID: PMC4039863  PMID: 24879829
Epidemiology; Mental Health
13.  Intentional and unintentional non-adherence to medications following an acute coronary syndrome: A longitudinal study 
Journal of Psychosomatic Research  2014;76(5):430-432.
Objective
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).
Method
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.
Results
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.
Conclusion
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.
doi:10.1016/j.jpsychores.2014.02.007
PMCID: PMC4005033  PMID: 24745787
Adherence; Acute coronary syndrome; Psychological; Intention
14.  The relationship between cortisol responses to laboratory stress and cortisol profiles in daily life 
Biological Psychology  2014;99(100):34-40.
Highlights
•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.
doi:10.1016/j.biopsycho.2014.02.010
PMCID: PMC4031630  PMID: 24582772
Stress reactivity; Laboratory–field; HPA axis; Cortisol
15.  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.
doi:10.1016/j.exger.2013.01.016
PMCID: PMC3626117  PMID: 23403382
telomeres; telomerase; cytomegalovirus; infections; Whitehall II
16.  Enjoyment of life and declining physical function at older ages: a longitudinal cohort study 
Background:
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.
Methods:
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.
Results:
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.
Interpretation:
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.
doi:10.1503/cmaj.131155
PMCID: PMC3940591  PMID: 24446463
17.  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.
Highlight
•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.
doi:10.1016/j.bbi.2013.11.008
PMCID: PMC3969589  PMID: 24239712
Depression; C-reactive protein; Coronary artery bypass grafting; Recovery
18.  The associations between unhealthy behaviours, mental stress, and low socio-economic status in an international comparison of representative samples from Thailand and England 
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1744-8603-10-10
PMCID: PMC3933467  PMID: 24555674
Psychological stress; Psychosocial deprivation; Health behavior; Social class
19.  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☆ 
Objective
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jpsychores.2013.10.019
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
20.  The Association Between Cortisol Response to Mental Stress and High-Sensitivity Cardiac Troponin T Plasma Concentration in Healthy Adults 
Objectives
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).
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1016/j.jacc.2013.05.070
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
21.  Objectively assessed sedentary time and type 2 diabetes mellitus: a case–control study 
Diabetologia  2013;56(12):2761-2762.
doi:10.1007/s00125-013-3051-5
PMCID: PMC3825498  PMID: 24078056
Accelerometry; Case–control; Physical activity; Sedentary; Type 2 diabetes mellitus
22.  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.
doi:10.1093/ageing/aft146
PMCID: PMC4081784  PMID: 24077751
discrimination; ageing; ageism; ELSA; England; older adults
23.  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.
Background
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.
Conclusions
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.
doi:10.1371/journal.pone.0067323
PMCID: PMC3688665  PMID: 23840664
24.  Associations of job strain and lifestyle risk factors with risk of coronary artery disease: a meta-analysis of individual participant data 
Background:
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.
Methods:
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).
Results:
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).
Interpretation:
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.
doi:10.1503/cmaj.121735
PMCID: PMC3680555  PMID: 23670152
25.  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.
Summary
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.
doi:10.1016/j.psyneuen.2012.07.012
PMCID: PMC3608033  PMID: 22877997
Shift work; Cortisol; Hpa axis; Time of waking; Sleep

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