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1.  Metabolically healthy obesity: What is the role of sedentary behaviour?☆ 
Preventive Medicine  2014;62(100):35-37.
Objective
The role of sedentary behaviour in metabolically healthy obesity is unknown. We examined cross-sectional differences in television viewing time across metabolic and obesity phenotypes, hypothesizing that healthy obese individuals spend less time viewing television than their unhealthy counterparts.
Methods
A nationally representative sample of 4931 older adults in England (mean age 65.1; SD = 8.9 years) was drawn from the 2008/9 wave of the English Longitudinal Study of Ageing. Average weekly television viewing time was derived from two questions about weekday and weekend viewing. Obesity was defined as body mass index ≥ 30 kg/m2, and metabolically healthy as having < 2 metabolic abnormalities (low HDL-cholesterol, high triglycerides, high blood pressure, hyperglycaemia, high inflammation).
Results
After adjusting for covariates including chronic illness, functional limitations and physical activity, mean weekly viewing times were 4.7 (95% confidence interval 2.9, 6.5), 5.8 (2.5, 9.0) and 7.8 (5.7, 9.8) h higher in unhealthy non-obese, healthy obese, and unhealthy obese groups respectively, compared to the healthy non-obese group (p for heterogeneity < 0.001).
Conclusions
A common type of leisure-time sedentary behaviour varies across metabolic and obesity phenotypes. However, healthy obesity is not explained through differences in leisure-time sedentary behaviour.
doi:10.1016/j.ypmed.2014.01.028
PMCID: PMC3995089  PMID: 24513171
Sedentary behaviour; Television viewing; Obesity; Metabolic health
2.  Associations between objectively assessed and self-reported sedentary time with mental health in adults: an analysis of data from the Health Survey for England 
BMJ Open  2014;4(3):e004580.
Objective
There is increasing interest in the association between sedentary behaviour and mental health, although most studies have relied solely on self-reported measures, thus making results prone to various biases. The aim was to compare associations between objectively assessed and self-reported sedentary time with mental health in adults.
Setting
Community dwelling population sample drawn from the 2008 Health Survey for England.
Participants
11 658 (self-report analysis) and 1947 (objective data) men and women.
Primary outcome
The 12-item General Health Questionnaire was administered to assess psychological distress. Sedentary and physical activity (exposure) was objectively measured using accelerometers (Actigraph GT1M) worn around the waist during waking hours for seven consecutive days.
Results
The highest tertile of objective sedentary time was associated with higher risk of psychological distress (multivariate adjusted OR=1.74, 95% CI 1.07 to 2.83), as was the highest tertile of self-reported total sitting time (OR=1.34, 95% CI 1.15 to 1.56). Self-reported, but not objective, moderate-to-vigorous physical activity was associated with lower risk of psychological distress. Only objective light-intensity activity was associated with lower risk of psychological distress.
Conclusions
Sedentary time is associated with adverse mental health.
doi:10.1136/bmjopen-2013-004580
PMCID: PMC3963121  PMID: 24650807
Mental Health; Epidemiology; Public Health
3.  A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts 
European Heart Journal  2012;34(10):750-758.
Aims
Cardiorespiratory fitness (CRF) is a key predictor of chronic disease, particularly cardiovascular disease (CVD), but its assessment usually requires exercise testing which is impractical and costly in most health-care settings. Non-exercise testing cardiorespiratory fitness (NET-F)-estimating methods are a less resource-demanding alternative, but their predictive capacity for CVD and total mortality has yet to be tested. The objective of this study is to examine the association of a validated NET-F algorithm with all-cause and CVD mortality.
Methods and results
The participants were 32 319 adults (14 650 men) aged 35–70 years who took part in eight Health Survey for England and Scottish Health Survey studies between 1994 and 2003. Non-exercise testing cardiorespiratory fitness (a metabolic equivalent of VO2max) was calculated using age, sex, body mass index (BMI), resting heart rate, and self-reported physical activity. We followed participants for mortality until 2008. Two thousand one hundred and sixty-five participants died (460 cardiovascular deaths) during a mean 9.0 [standard deviation (SD) = 3.6] year follow-up. After adjusting for potential confounders including diabetes, hypertension, smoking, social class, alcohol, and depression, a higher fitness score according to the NET-F was associated with a lower risk of mortality from all-causes (hazard ratio per SD increase in NET-F 0.85, 95% confidence interval: 0.78–0.93 in men; 0.88, 0.80–0.98 in women) and CVD (men: 0.75, 0.63–0.90; women: 0.73, 0.60–0.92). Non-exercise testing cardiorespiratory fitness had a better discriminative ability than any of its components (CVD mortality c-statistic: NET-F = 0.70–0.74; BMI = 0.45–0.59; physical activity = 0.60–0.64; resting heart rate = 0.57–0.61). The sensitivity of the NET-F algorithm to predict events occurring in the highest risk quintile was better for CVD (0.49 in both sexes) than all-cause mortality (0.44 and 0.40 for men and women, respectively). The specificity for all-cause and CVD mortality ranged between 0.80 and 0.82. The net reclassification improvement of CVD mortality risk (vs. a standardized aggregate score of the modifiable components of NET-F) was 27.2 and 21.0% for men and women, respectively.
Conclusion
The CRF-estimating method NET-F that does not involve exercise testing showed consistent associations with all-cause and cardiovascular mortality, and it had good discrimination and excellent risk reclassification improvement. As such, it merits further attention as a practical and potentially and useful risk prediction tool.
doi:10.1093/eurheartj/ehs097
PMCID: PMC3590456  PMID: 22555215
Epidemiology; Non-exercise testing; Cardiorespiratory fitness; Cardiovascular disease; Physical activity; Health Survey for England
4.  Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts 
F1000Research  2014;2:233.
Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.
 
Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.
 
Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
doi:10.12688/f1000research.2-233.v2
PMCID: PMC3938244  PMID: 24627793
5.  Physical activity and inflammatory markers over 10 years follow up in men and women from the Whitehall II cohort study 
Circulation  2012;126(8):928-933.
Background
Inflammatory processes are putative mechanisms underlying the cardio-protective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period.
Methods and Results
Participants were 4289 men and women (mean age 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 hours per week moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower CRP and IL6 levels and this difference remained stable over time. In comparison to participants that rarely adhered to physical activity guidelines over the 10 years follow-up, the high adherence group displayed lower logeCRP (β=−0.07, 95% CI, −0.12, −0.02) and logeIL-6 (β=−0.07, 95% CI, −0.10, −0.03) at follow up after adjustment for a range of covariates. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hours/wk displayed lower loge CRP (B coefficient =−0.05, 95% CI, −0.10, −0.001) and loge IL-6 (B coefficient =−0.06, 95% CI, −0.09, −0.03) at follow up.
Conclusions
Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the pro-inflammatory state seen with ageing.
doi:10.1161/CIRCULATIONAHA.112.103879
PMCID: PMC3890998  PMID: 22891048
Ageing; C-reactive protein; exercise; physical activity; inflammation
6.  Watching sport on television, physical activity, and risk of obesity in older adults 
BMC Public Health  2014;14:10.
Background
Television (TV) viewing has been associated with obesity although the effects of specific TV content on health and other behaviours remains unknown. We examined the association between watching sport on TV, physical activity levels, and risk of obesity.
Methods
We studied 6,733 (aged 64.9 ± 9.2 yrs) men and women from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Data were collected on self reported TV time and content, and physical activity. Nurses measured height and weight for the calculation of body mass index.
Results
On average, participants reported viewing TV for 5.3 ± 4.1 hours per day and 30.3% of the sample watched sport on TV at least twice a week. There was no association between watching sport and physical activity levels. Participants that watched sports every day were at higher risk of obesity [odds ratio = 1.39, 95% CI, 1.15, 1.68) after adjustment for age, sex, smoking, alcohol, physical activity, total TV time, disability, and self-rated health.
Conclusions
Watching elite athletes may have no role in the promotion of physical activity in older adults, which has implications for staging large sporting events with physical activity legacy promises.
doi:10.1186/1471-2458-14-10
PMCID: PMC3890601  PMID: 24400697
Ageing; Epidemiology; Health promotion; Obesity; Physical activity; Sedentary
7.  Socioeconomic status as a risk factor for dementia death: individual participant meta-analysis of 86 508 men and women from the UK* 
Background
Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base.
Aims
To examine the association between socioeconomic status in early life and adulthood with later dementia death.
Method
Individual participant meta-analysis of 11 prospective cohort studies (1994-2004, n = 86 508).
Results
Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ⩽14 v. age ⩾16: HR = 1.76, 95% CI 1.23-2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women.
Conclusions
Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities.
doi:10.1192/bjp.bp.112.119479
PMCID: PMC3696876  PMID: 23818534
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.  Active buildings: modelling physical activity and movement in office buildings. An observational study protocol 
BMJ Open  2013;3(11):e004103.
Introduction
Health benefits of regular participation in physical activity are well documented but population levels are low. Office layout, and in particular the number and location of office building destinations (eg, print and meeting rooms), may influence both walking time and characteristics of sitting time. No research to date has focused on the role that the layout of the indoor office environment plays in facilitating or inhibiting step counts and characteristics of sitting time. The primary aim of this study was to investigate associations between office layout and physical activity, as well as sitting time using objective measures.
Methods and analysis
Active buildings is a unique collaboration between public health, built environment and computer science researchers. The study involves objective monitoring complemented by a larger questionnaire arm. UK office buildings will be selected based on a variety of features, including office floor area and number of occupants. Questionnaires will include items on standard demographics, well-being, physical activity behaviour and putative socioecological correlates of workplace physical activity. Based on survey responses, approximately 30 participants will be recruited from each building into the objective monitoring arm. Participants will wear accelerometers (to monitor physical activity and sitting inside and outside the office) and a novel tracking device will be placed in the office (to record participant location) for five consecutive days. Data will be analysed using regression analyses, as well as novel agent-based modelling techniques.
Ethics and dissemination
The results of this study will be disseminated through peer-reviewed publications and scientific presentations. Ethical approval was obtained through the University College London Research Ethics Committee (Reference number 4400/001).
doi:10.1136/bmjopen-2013-004103
PMCID: PMC3831099  PMID: 24227873
Physical Activity; Sedentary Behaviour; Built Environment; Agent-based models; Office Buildings
10.  Chronic inflammation as a determinant of future aging phenotypes  
Background:
The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women.
Methods:
We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study’s baseline (1997–1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007–2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants).
Results:
Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38–0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15–2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58–3.80).
Interpretation:
Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.
doi: 10.1503/cmaj.122072
PMCID: PMC3826354  PMID: 24043651
11.  Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts 
F1000Research  2013;2:233.
Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.
 
Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.
 
Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
doi:10.12688/f1000research.2-233.v1
PMCID: PMC3938244  PMID: 24627793
12.  Diabetes Risk Factors, Diabetes Risk Algorithms, and the Prediction of Future Frailty: The Whitehall II Prospective Cohort Study 
Objective
To examine whether established diabetes risk factors and diabetes risk algorithms are associated with future frailty.
Design
Prospective cohort study. Risk algorithms at baseline (1997–1999) were the Framingham Offspring, Cambridge, and Finnish diabetes risk scores.
Setting
Civil service departments in London, United Kingdom.
Participants
There were 2707 participants (72% men) aged 45 to 69 years at baseline assessment and free of diabetes.
Measurements
Risk factors (age, sex, family history of diabetes, body mass index, waist circumference, systolic and diastolic blood pressure, antihypertensive and corticosteroid treatments, history of high blood glucose, smoking status, physical activity, consumption of fruits and vegetables, fasting glucose, HDL-cholesterol, and triglycerides) were used to construct the risk algorithms. Frailty, assessed during a resurvey in 2007–2009, was denoted by the presence of 3 or more of the following indicators: self-reported exhaustion, low physical activity, slow walking speed, low grip strength, and weight loss; “prefrailty” was defined as having 2 or fewer of these indicators.
Results
After a mean follow-up of 10.5 years, 2.8% of the sample was classified as frail and 37.5% as prefrail. Increased age, being female, stopping smoking, low physical activity, and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty. The Cambridge and Finnish diabetes risk scores were associated with frailty/prefrailty with odds ratios per 1 SD increase (disadvantage) in score of 1.18 (95% confidence interval: 1.09–1.27) and 1.27 (1.17–1.37), respectively.
Conclusion
Selected diabetes risk factors and risk scores are associated with subsequent frailty. Risk scores may have utility for frailty prediction in clinical practice.
doi:10.1016/j.jamda.2013.08.016
PMCID: PMC3820037  PMID: 24103860
Aging; frailty; diabetes risk scores; diabetes risk factors
13.  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
14.  Objectively assessed sedentary time and type 2 diabetes mellitus: a case–control study 
Diabetologia  2013;56:2761-2762.
doi:10.1007/s00125-013-3051-5
PMCID: PMC3825498  PMID: 24078056
Accelerometry; Case–control; Physical activity; Sedentary; Type 2 diabetes mellitus
15.  Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts 
PLoS ONE  2013;8(9):e73753.
Background
There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts.
Methods
The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education.
Results
In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52–0.89) and cancer (HR = 0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity.
Conclusions
Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women.
doi:10.1371/journal.pone.0073753
PMCID: PMC3784430  PMID: 24086292
16.  The Bidirectional Association between Depressive Symptoms and Gait Speed: Evidence from the English Longitudinal Study of Ageing (ELSA) 
PLoS ONE  2013;8(7):e68632.
Background
Depressive symptoms and physical performance are inversely associated, but it is unclear whether their association is bidirectional. We examined whether the association between depressive symptoms and physical performance measured using gait speed is bidirectional.
Methods
We used a national sample of 4,581 community-dwelling people aged 60 years and older from the English Longitudinal Study of Ageing (from 2002–03 to 2008-09). We fitted Generalized Estimating Equation (GEE) regression models to analyse repeated measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a score of ≥4 on the eight-item Center for Epidemiological Studies-Depression scale).
Results
Slower gait speed was associated with elevated depressive symptoms both concurrently and two years later. After adjustment for previous depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and cognitive factors the concurrent association was partially explained (Odds Ratio [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to 1.00). Elevated depressive symptoms were associated with slower gait speed. Full adjustment for covariates (including previous gait speed) partially explained both the concurrent (β regression coefficient [β] -0.038, 95% CI, -0.050 to -0.026, for participants with elevated depressive symptoms compared with those with no or one symptom) and the two-year lagged associations (β -0.017, 95% CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of two or three on the eight-item Center for Epidemiological Studies-Depression scale) were also associated with slower gait speed. Full adjustment for covariates partially explained both the concurrent (β -0.029, 95% CI, -0.039 to -0.019, for participants with subthreshold symptoms compared with those with no or one symptom) and the two-year lagged associations (β -0.011, 95% CI, -0.021 to -0.001).
Conclusions
The inverse association between gait speed and depressive symptoms appears to be bidirectional.
doi:10.1371/journal.pone.0068632
PMCID: PMC3706406  PMID: 23874698
17.  Measures of frailty in population-based studies: an overview 
BMC Geriatrics  2013;13:64.
Background
Although research productivity in the field of frailty has risen exponentially in recent years, there remains a lack of consensus regarding the measurement of this syndrome. This overview offers three services: first, we provide a comprehensive catalogue of current frailty measures; second, we evaluate their reliability and validity; third, we report on their popularity of use.
Methods
In order to identify relevant publications, we searched MEDLINE (from its inception in 1948 to May 2011); scrutinized the reference sections of the retrieved articles; and consulted our own files. An indicator of the frequency of use of each frailty instrument was based on the number of times it had been utilized by investigators other than the originators.
Results
Of the initially retrieved 2,166 papers, 27 original articles described separate frailty scales. The number (range: 1 to 38) and type of items (range of domains: physical functioning, disability, disease, sensory impairment, cognition, nutrition, mood, and social support) included in the frailty instruments varied widely. Reliability and validity had been examined in only 26% (7/27) of the instruments. The predictive validity of these scales for mortality varied: for instance, hazard ratios/odds ratios (95% confidence interval) for mortality risk for frail relative to non-frail people ranged from 1.21 (0.78; 1.87) to 6.03 (3.00; 12.08) for the Phenotype of Frailty and 1.57 (1.41; 1.74) to 10.53 (7.06; 15.70) for the Frailty Index. Among the 150 papers which we found to have used at least one of the 27 frailty instruments, 69% (n = 104) reported on the Phenotype of Frailty, 12% (n = 18) on the Frailty Index, and 19% (n = 28) on one of the remaining 25 instruments.
Conclusions
Although there are numerous frailty scales currently in use, reliability and validity have rarely been examined. The most evaluated and frequently used measure is the Phenotype of Frailty.
doi:10.1186/1471-2318-13-64
PMCID: PMC3710231  PMID: 23786540
Frailty; Frail elderly; Measure; Overview; Reliability; Validity
18.  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
19.  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
20.  Screen-Based Sedentary Behavior, Physical Activity, and Muscle Strength in the English Longitudinal Study of Ageing 
PLoS ONE  2013;8(6):e66222.
Background
Sarcopenia is associated with loss of independence and ill-health in the elderly although the causes remain poorly understood. We examined the association between two screen-based leisure time sedentary activities (daily TV viewing time and internet use) and muscle strength.
Methods and Results
We studied 6228 men and women (aged 64.9±9.1 yrs) from wave 4 (2008-09) of the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Muscle strength was assessed by a hand grip test and the time required to complete five chair rises. TV viewing and internet usage were inversely associated with one another. Participants viewing TV ≥6hrs/d had lower grip strength (Men, B = −1.20 kg, 95% CI, −2.26, −0.14; Women, −0.75 kg, 95% CI, −1.48, −0.03) in comparison to <2hrs/d TV, after adjustment for age, physical activity, smoking, alcohol, chronic disease, disability, depressive symptoms, social status, and body mass index. In contrast, internet use was associated with higher grip strength (Men, B = 2.43 kg, 95% CI, 1.74, 3.12; Women, 0.76 kg, 95% CI, 0.32, 1.20). These associations persisted after mutual adjustment for both types of sedentary behaviour.
Conclusions
In older adults, the association between sedentary activities and physical function is context specific (TV viewing vs. computer use). Adverse effects of TV viewing might reflect the prolonged sedentary nature of this behavior.
doi:10.1371/journal.pone.0066222
PMCID: PMC3670922  PMID: 23755302
21.  Does Overall Diet in Midlife Predict Future Aging Phenotypes? A Cohort Study 
The American Journal of Medicine  2013;126(5):411-419.e3.
Background
The impact of diet on specific age-related diseases has been studied extensively, but few investigations have adopted a more holistic approach to determine the association of diet with overall health at older ages. We examined whether diet, assessed in midlife, using dietary patterns and adherence to the Alternative Healthy Eating Index (AHEI), is associated with aging phenotypes, identified after a mean 16-year follow-up.
Methods
Data were drawn from the Whitehall II cohort study of 5350 adults (age 51.3 ± 5.3 years, 29.4% women). Diet was assessed at baseline (1991-1993). Mortality, chronic diseases, and functioning were ascertained from hospital data, register linkage, and screenings every 5 years and were used to create 5 outcomes at follow-up: ideal aging (free of chronic conditions and high performance in physical, mental, and cognitive functioning tests; 4%), nonfatal cardiovascular event (7.3%), cardiovascular death (2.8%), noncardiovascular death (12.7%), and normal aging (73.2%).
Results
Low adherence to the AHEI was associated with an increased risk of cardiovascular and noncardiovascular death. In addition, participants with a “Western-type” diet (characterized by high intakes of fried and sweet food, processed food and red meat, refined grains, and high-fat dairy products) had lower odds of ideal aging (odds ratio for top vs bottom tertile: 0.58; 95% confidence interval, 0.36-0.94; P = .02), independently of other health behaviors.
Conclusions
By considering healthy aging as a composite of cardiovascular, metabolic, musculoskeletal, respiratory, mental, and cognitive function, the present study offers a new perspective on the impact of diet on aging phenotypes.
doi:10.1016/j.amjmed.2012.10.028
PMCID: PMC3743043  PMID: 23582933
Aging; Cognitive functioning; Dietary patterns; Diet quality indices; Mortality; Nutritional epidemiology; Overall diet; Physical functioning
22.  Risk of future depression in people who are obese but metabolically healthy: The English Longitudinal Study of Ageing 
Molecular psychiatry  2012;17(9):940-945.
There is some evidence to suggest that obesity is a risk factor for the development of depression, although this is not a universal finding. This discordance might be ascribed to the existence of a ‘healthy obese phenotype’– that is, obesity in the absence of the associated burden of cardio-metabolic risk factors. We examined whether the association of obesity with depressive symptoms is dependent on the individual’s metabolic health. Participants were 3851 men and women (aged 63.0 ± 8.9 yrs, 45.1% men) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Obesity was defined as body mass index ≥ 30 kg/m2. Based on blood pressure, HDL-cholesterol, triglycerides, glycated haemoglobin, and C-reactive protein, participants were classified as ‘metabolically healthy’ (0 or 1 metabolic abnormality) or ‘unhealthy’ (≥ 2 metabolic abnormalities). Depressive symptoms were assessed at baseline and at 2 years follow up using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale. Obesity prevalence was 27.5%, but 34.3% of this group was categorized as metabolically healthy at baseline. Relative to non-obese healthy participants, after adjustment for baseline CES-D score and other covariates, the metabolically unhealthy obese participants had elevated risk of depressive symptoms at follow-up (odds ratio [OR] = 1.50, 95% CI, 1.05–2.15), although the metabolically healthy obese did not (OR = 1.38, 95% CI, 0.88–2.17). The association between obesity and risk of depressive symptoms appears to be partly dependent on metabolic health, although further work is required to confirm these findings.
doi:10.1038/mp.2012.30
PMCID: PMC3428506  PMID: 22525487
24.  Association of C-Reactive Protein With Cardiovascular Disease Mortality According to Diabetes Status 
Diabetes Care  2012;35(2):396-403.
OBJECTIVE
C-reactive protein (CRP) is associated with the risk of cardiovascular disease (CVD); whether the effects are modified by diabetes status still is unclear. This study investigated these issues and assessed the added value of CRP to predictions.
RESEARCH DESIGN AND METHODS
Participants were drawn from representative samples of adults living in England and Scotland. Cox proportional hazards regression models were used to relate baseline plasma CRP with all-cause and CVD mortality during follow-up in men and women with and without diabetes. The added value of CRP to the predictions was assessed through c-statistic comparison and relative integrated discrimination improvement.
RESULTS
A total of 25,979 participants (4.9% with diabetes) were followed for a median of 93 months, during which period there were 2,767 deaths (957 from CVD). CRP (per SD loge) was associated with a 53% (95% CI 43–64) and 43% (38–49) higher risk of cardiovascular and all-cause mortality, respectively. These associations were log linear and did not differ according to diabetes status (both P ≥ 0.08 for interaction), sex, and other risk factors. Adding CRP to conventional risk factors improved predictions overall and separately by diabetes status but not for CVD mortality, although such improvements only were marginal based on several discrimination statistics.
CONCLUSIONS
The association between CRP and CVD was similar across diabetes status, and the effects are broadly similar across levels of other conventional risk factors.
doi:10.2337/dc11-1588
PMCID: PMC3263864  PMID: 22210562

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