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1.  The Joint Effect of Sleep Duration and Disturbed Sleep on Cause-Specific Mortality: Results from the Whitehall II Cohort Study 
PLoS ONE  2014;9(4):e91965.
Background
Both sleep duration and sleep quality are related to future health, but their combined effects on mortality are unsettled. We aimed to examine the individual and joint effects of sleep duration and sleep disturbances on cause-specific mortality in a large prospective cohort study.
Methods
We included 9,098 men and women free of pre-existing disease from the Whitehall II study, UK. Sleep measures were self-reported at baseline (1985–1988). Participants were followed until 2010 in a nationwide death register for total and cause-specific (cardiovascular disease, cancer and other) mortality.
Results
There were 804 deaths over a mean 22 year follow-up period. In men, short sleep (≤6 hrs/night) and disturbed sleep were not independently associated with CVD mortality, but there was an indication of higher risk among men who experienced both (HR = 1.57; 95% CI: 0.96–2.58). In women, short sleep and disturbed sleep were independently associated with CVD mortality, and women with both short and disturbed sleep experienced a much higher risk of CVD mortality (3.19; 1.52–6.72) compared to those who slept 7–8 hours with no sleep disturbances; equivalent to approximately 90 additional deaths per 100,000 person years. Sleep was not associated with death due to cancer or other causes.
Conclusion
Both short sleep and disturbed sleep are independent risk factors for CVD mortality in women and future studies on sleep may benefit from assessing disturbed sleep in addition to sleep duration in order to capture health-relevant features of inadequate sleep.
doi:10.1371/journal.pone.0091965
PMCID: PMC3974730  PMID: 24699341
2.  Predicting cognitive decline 
Neurology  2013;80(14):1300-1306.
Objective:
Our aim was to compare 2 Framingham vascular risk scores with a dementia risk score in relation to 10-year cognitive decline in late middle age.
Methods:
Participants were men and women with mean age of 55.6 years at baseline, from the Whitehall II study, a longitudinal British cohort study. We compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score that uses risk factors in midlife to estimate risk of late-life dementia. Cognitive tests included reasoning, memory, verbal fluency, vocabulary, and global cognition, assessed 3 times over 10 years.
Results:
Higher cardiovascular disease risk and higher stroke risk were associated with greater cognitive decline in all tests except memory; higher dementia risk was associated with greater decline in reasoning, vocabulary, and global cognitive scores. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline; these differences were statistically significant for semantic fluency and global cognitive scores. For example, cardiovascular disease risk was associated with −0.06 SD (95% confidence interval [CI] = −0.08, −0.05) decline in the global cognitive scores over 10 years whereas dementia risk was associated with −0.03 SD (95% CI = −0.04, −0.01) decline (difference in β coefficients = 0.03; 95% CI = 0.01, 0.05).
Conclusions:
The CAIDE dementia and Framingham risk scores predict cognitive decline in late middle age but the Framingham risk scores may have an advantage over the dementia risk score for use in primary prevention for assessing risk of cognitive decline and targeting of modifiable risk factors.
doi:10.1212/WNL.0b013e31828ab370
PMCID: PMC3656460  PMID: 23547265
3.  Glycemia, Insulin Resistance, Insulin Secretion, and Risk of Depressive Symptoms in Middle Age 
Diabetes Care  2013;36(4):928-934.
OBJECTIVE
The extent to which abnormal glucose metabolism increases the risk of depression remains unclear. In this study, we investigated prospective associations of levels of fasting glucose and fasting insulin and indices of insulin resistance and secretion with subsequent new-onset depressive symptoms (DepS).
RESEARCH DESIGN AND METHODS
In this prospective cohort study of 3,145 adults from the Whitehall II Study (23.5% women, aged 60.6 ± 5.9 years), baseline examination included fasting glucose and insulin level, the homeostasis model assessment of insulin resistance (HOMA2-%IR), and the homeostasis model assessment of β-cell insulin secretion (HOMA2-%B). DepS (Center for Epidemiologic Studies Depression Scale ≥16 or use of antidepressive drugs) were assessed at baseline and at 5-year follow-up.
RESULTS
Over the 5-year follow-up, DepS developed in 142 men and 84 women. Women in the lowest quintile of insulin secretion (HOMA2-%B ≤55.3%) had 2.18 (95% CI 1.25–3.78) times higher odds of developing DepS than those with higher insulin secretion. This association was not accounted for by inflammatory markers, cortisol secretion, or menopausal status and hormone replacement therapy. Fasting insulin measures were not associated with DepS in men, and fasting glucose measures were not associated with new-onset DepS in either sex.
CONCLUSIONS
Low insulin secretion appears to be a risk factor for DepS in middle-aged women, although further work is required to confirm this finding.
doi:10.2337/dc12-0239
PMCID: PMC3609527  PMID: 23230097
5.  Job insecurity and incident coronary heart disease: the Whitehall II prospective cohort study 
Atherosclerosis  2013;227(1):178-181.
Objective
This study uses a prospective design to examine the association between self-reported job insecurity and incident coronary heart disease; an association which has been little investigated previously.
Methods
Participants were 4174 British civil servants (1236 women and 2938 men), aged 42 to 56 with self-reported data on job insecurity and free from coronary heart disease at baseline (1995-6). These participants were followed until 2002-4, an average of 8.6 years, for incident fatal coronary heart disease, clinically verified incident non-fatal myocardial infarction, or definite angina (a total of 168 events).
Results
Cox proportional hazard models adjusted for socio-demographic characteristics showed job insecurity to be associated with a 1.42-fold (95% CI, 1.05-1.93) risk of incident coronary heart disease compared with secure employment. Adjustment for physiological and behavioral cardiovascular risk factors had little effect on this estimate; 1.38 (1.01-1.88).
Conclusion
This study suggests that job insecurity may adversely affect coronary health.
doi:10.1016/j.atherosclerosis.2012.12.027
PMCID: PMC3940189  PMID: 23332775
job insecurity; stress; incident coronary heart disease; angina; middle-aged; prospective
6.  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
7.  Extending Employment beyond the Pensionable Age: A Cohort Study of the Influence of Chronic Diseases, Health Risk Factors, and Working Conditions 
PLoS ONE  2014;9(2):e88695.
Background
In response to the economic consequences of ageing of the population, governments are seeking ways with which people might work into older age. We examined the association of working conditions and health with extended employment (defined as >6 months beyond the pensionable age) in a cohort of older, non-disabled employees who have reached old-age retirement.
Methods
A total of 4,677 Finnish employees who reached their old-age pensionable date between 2005 and 2011 (mean age 59.8 years in 2005, 73% women) had their survey responses before pensionable age linked to national health and pension registers, resulting in a prospective cohort study.
Results
In all, 832 participants (17.8%) extended their employment by more than 6 months beyond the pensionable date. After multivariable adjustment, the following factors were associated with extended employment: absence of diagnosed mental disorder (OR 1.25, 95% confidence interval = 1.01–1.54) and psychological distress (OR 1.68; 1.35–2.08) and of the work characteristics, high work time control (OR 2.31; 1.88–2.84). The projected probability of extended employment was 21.3% (19.5–23.1) among those free of psychiatric morbidity and with high work time control, while the corresponding probability was only 9.2% (7.4–11.4) among those with both psychiatric morbidity and poor work time control. The contribution of chronic somatic diseases was modest.
Conclusions
In the present study, good mental health in combination with the opportunity to control work time seem to be key factors in extended employment into older age. In addition, high work time control might promote work life participation irrespective of employees' somatic disease status.
doi:10.1371/journal.pone.0088695
PMCID: PMC3929527  PMID: 24586372
8.  Job Strain and the Risk of Inflammatory Bowel Diseases: Individual-Participant Meta-Analysis of 95 000 Men and Women 
PLoS ONE  2014;9(2):e88711.
Background and Aims
Many clinicians, patients and patient advocacy groups believe stress to have a causal role in inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. However, this is not corroborated by clear epidemiological research evidence. We investigated the association between work-related stress and incident Crohn's disease and ulcerative colitis using individual-level data from 95 000 European adults.
Methods
We conducted individual-participant data meta-analyses in a set of pooled data from 11 prospective European studies. All studies are a part of the IPD-Work Consortium. Work-related psychosocial stress was operationalised as job strain (a combination of high demands and low control at work) and was self-reported at baseline. Crohn's disease and ulcerative colitis were ascertained from national hospitalisation and drug reimbursement registers. The associations between job strain and inflammatory bowel disease outcomes were modelled using Cox proportional hazards regression. The study-specific results were combined in random effects meta-analyses.
Results
Of the 95 379 participants who were free of inflammatory bowel disease at baseline, 111 men and women developed Crohn's disease and 414 developed ulcerative colitis during follow-up. Job strain at baseline was not associated with incident Crohn's disease (multivariable-adjusted random effects hazard ratio: 0.83, 95% confidence interval: 0.48, 1.43) or ulcerative colitis (hazard ratio: 1.06, 95% CI: 0.76, 1.48). There was negligible heterogeneity among the study-specific associations.
Conclusions
Our findings suggest that job strain, an indicator of work-related stress, is not a major risk factor for Crohn's disease or ulcerative colitis.
doi:10.1371/journal.pone.0088711
PMCID: PMC3928274  PMID: 24558416
9.  Patterns of Obesity Development before the Diagnosis of Type 2 Diabetes: The Whitehall II Cohort Study 
PLoS Medicine  2014;11(2):e1001602.
Examining patterns of change in body mass index (BMI) and other cardiometabolic risk factors in individuals during the years before they were diagnosed with diabetes, Kristine Færch and colleagues report that few of them experienced dramatic BMI changes.
Please see later in the article for the Editors' Summary
Background
Patients with type 2 diabetes vary greatly with respect to degree of obesity at time of diagnosis. To address the heterogeneity of type 2 diabetes, we characterised patterns of change in body mass index (BMI) and other cardiometabolic risk factors before type 2 diabetes diagnosis.
Methods and Findings
We studied 6,705 participants from the Whitehall II study, an observational prospective cohort study of civil servants based in London. White men and women, initially free of diabetes, were followed with 5-yearly clinical examinations from 1991–2009 for a median of 14.1 years (interquartile range [IQR]: 8.7–16.2 years). Type 2 diabetes developed in 645 (1,209 person-examinations) and 6,060 remained free of diabetes during follow-up (14,060 person-examinations). Latent class trajectory analysis of incident diabetes cases was used to identify patterns of pre-disease BMI. Associated trajectories of cardiometabolic risk factors were studied using adjusted mixed-effects models. Three patterns of BMI changes were identified. Most participants belonged to the “stable overweight” group (n = 604, 94%) with a relatively constant BMI level within the overweight category throughout follow-up. They experienced slightly worsening of beta cell function and insulin sensitivity from 5 years prior to diagnosis. A small group of “progressive weight gainers” (n = 15) exhibited a pattern of consistent weight gain before diagnosis. Linear increases in blood pressure and an exponential increase in insulin resistance a few years before diagnosis accompanied the weight gain. The “persistently obese” (n = 26) were severely obese throughout the whole 18 years before diabetes diagnosis. They experienced an initial beta cell compensation followed by loss of beta cell function, whereas insulin sensitivity was relatively stable. Since the generalizability of these findings is limited, the results need confirmation in other study populations.
Conclusions
Three patterns of obesity changes prior to diabetes diagnosis were accompanied by distinct trajectories of insulin resistance and other cardiometabolic risk factors in a white, British population. While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis. These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 350 million people have diabetes, a metabolic disorder characterized by high amounts of glucose (sugar) in the blood. Blood sugar levels are normally controlled by insulin, a hormone released by the pancreas after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes) blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes, which was previously called adult-onset diabetes, can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. Long-term complications, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes. The number of people with diabetes is expected to increase dramatically over the next decades, coinciding with rising obesity rates in many countries. To better understand diabetes development, to identify people at risk, and to find ways to prevent the disease are urgent public health goals.
Why Was This Study Done?
It is known that people who are overweight or obese have a higher risk of developing diabetes. Because of this association, a common assumption is that people who experienced recent weight gain are more likely to be diagnosed with diabetes. In this prospective cohort study (an investigation that records the baseline characteristics of a group of people and then follows them to see who develops specific conditions), the researchers tested the hypothesis that substantial weight gain precedes a diagnosis of diabetes and explored more generally the patterns of body weight and composition in the years before people develop diabetes. They then examined whether changes in body weight corresponded with changes in other risk factors for diabetes (such as insulin resistance), lipid profiles and blood pressure.
What Did the Researchers Do and Find?
The researchers studied participants from the Whitehall II study, a prospective cohort study initiated in 1985 to investigate the socioeconomic inequalities in disease. Whitehall II enrolled more than 10,000 London-based government employees. Participants underwent regular health checks during which their weight and height were measured, blood tests were done, and they filled out questionnaires for other relevant information. From 1991 onwards, participants were tested every five years for diabetes. The 6,705 participants included in this study were initially free of diabetes, and most of them were followed for at least 14 years. During the follow-up, 645 participants developed diabetes, while 6,060 remained free of the disease.
The researchers used a statistical tool called “latent class trajectory analysis” to study patterns of changes in body mass index (BMI) in the years before people developed diabetes. BMI is a measure of human obesity based on a person's weight and height. Latent class trajectory analysis is an unbiased way to subdivide a number of people into groups that differ based on specified parameters. In this case, the researchers wanted to identify several groups among all the people who eventually developed diabetes each with a distinct pattern of BMI development. Having identified such groups, they also examined how a variety of tests associated with diabetes risk, and risks for heart disease and stroke changed in the identified groups over time.
They identified three different patterns of BMI changes in the 645 participants who developed diabetes. The vast majority (606 individuals, or 94%) belonged to a group they called “stable-overweight.” These people showed no dramatic change in their BMI in the years before they were diagnosed. They were overweight when they first entered the study and gained or lost little weight during the follow-up years. They showed only minor signs of insulin-resistance, starting five years before they developed diabetes. A second, much smaller group of 15 people gained weight consistently in the years before diagnosis. As they were gaining weight, these people also had raises in blood pressure and substantial gains in insulin resistance. The 26 remaining participants who formed the third group were persistently obese for the entire time they participated in the study, in some cases up to 18 years before they were diagnosed with diabetes. They had some signs of insulin resistance in the years before diagnosis, but not the substantial gain often seen as the hallmark of “pre-diabetes.”
What Do These Findings Mean?
These results suggest that diabetes development is a complicated process, and one that differs between individuals who end up with the disease. They call into question the common notion that most people who develop diabetes have recently gained a lot of weight or are obese. A substantial rise in insulin resistance, another established risk factor for diabetes, was only seen in the smallest of the groups, namely the people who gained weight consistently for years before they were diagnosed. When the scientists applied a commonly used predictor of diabetes called the “Framingham diabetes risk score” to their largest “stably overweight” group, they found that these people were not classified as having a particularly high risk, and that their risk scores actually declined in the last five years before their diabetes diagnosis. This suggests that predicting diabetes in this group might be difficult.
The researchers applied their methodology only to this one cohort of white civil servants in England. Before drawing more firm conclusions on the process of diabetes development, it will be important to test whether similar results are seen in other cohorts and among more diverse individuals. If the three groups identified here are found in other cohorts, another question is whether they are as unequal in size as in this example. And if they are, can the large group of stably overweight people be further subdivided in ways that suggest specific mechanisms of disease development? Even without knowing how generalizable the provocative findings of this study are, they should stimulate debate on how to identify people at risk for diabetes and how to prevent the disease or delay its onset.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001602.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes; it includes people's stories about diabetes
The charity Diabetes UK also provides detailed information about diabetes for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the charity Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
More information about the Whitehall II study is available
doi:10.1371/journal.pmed.1001602
PMCID: PMC3921118  PMID: 24523667
10.  Living in proximity of a bar and risky alcohol behaviours: A longitudinal study 
Addiction (Abingdon, England)  2012;108(2):320-328.
Aims
We examined whether distance from home to the nearest bar, i.e. alcohol outlet permitting consumption on the premises, is associated with risky alcohol behaviours.
Design
Cross-sectional and longitudinal study.
Setting and Participants
The cross-sectional data consisted of 78 858 and the longitudinal data of 54 778 Finnish Public Sector Study participants in between 2000 and 2009 [mean follow-up 6.8 years (SD=2.0)].
Measurements
Distances from home to the nearest bar were calculated using Global Positioning System-coordinates. The outcome variables were heavy alcohol use (drinking above the weekly guidelines) and extreme drinking occasions (passing out due to alcohol use). We used binomial logistic regression in cross-sectional analyses and in longitudinal mixed effects (between-individual) analyses. Conditional logistic regression was used in longitudinal fixed effects (within-individual) analyses.
Findings
Cross-sectionally, the likelihood of an extreme drinking occasion and heavy use was higher among those who resided <1 vs. ≥1 km from a bar. Longitudinally, between individuals, a decrease from >1 km to ≤1 km in distance was weakly associated with an extreme drinking occasion (1.18, 95% CI 0.98–1.41), and heavy use (1.12, 95% CI 0.97–1.29). Within-individual, the odds ratio for becoming a heavy user was 1.17 (95% CI, 1.02–1.34), per 1 km decrease in log-transformed continuous distance, the corresponding odds ratio for an extreme drinking occasion was 1.03 (95% CI, 0.89–1.18).
Conclusions
Moving place of residence close to or far from a bar appears to be associated with a small corresponding increase or decrease in risky alcohol behaviour.
doi:10.1111/j.1360-0443.2012.04053.x
PMCID: PMC3529803  PMID: 22897634
11.  Prediabetes: A high-risk state for developing diabetes 
Lancet  2012;379(9833):2279-2290.
Summary
Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.
doi:10.1016/S0140-6736(12)60283-9
PMCID: PMC3891203  PMID: 22683128
12.  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
13.  Adiponectin Trajectories Before Type 2 Diabetes Diagnosis 
Diabetes Care  2012;35(12):2540-2547.
OBJECTIVE
The role of adiponectin in the natural history of diabetes is not well characterized. We set out to characterize prediagnosis trajectories of adiponectin in individuals who develop type 2 diabetes.
RESEARCH DESIGN AND METHODS
In a case-cohort study (335 incident diabetes case and 2,474 noncase subjects) nested in the Whitehall II study, serum adiponectin was measured up to three times per participant (1991–1993, 1997–1999, and 2003–2004). Multilevel models adjusted for age and ethnicity were fitted to assess 13-year trajectories of log-transformed adiponectin preceding diabetes diagnosis or a randomly selected time point during follow-up (year0) based on 755/5,095 (case/noncase) person-examinations.
RESULTS
Adiponectin levels were lower in diabetes case than in noncase subjects (median 7,141 [interquartile range 5,187–10,304] vs. 8,818 [6,535–12,369] ng/mL at baseline, P < 0.0001). Control subjects showed a modest decline in adiponectin throughout follow-up (0.3% per year, P < 0.0001) at higher levels in women than in men (difference at year0: 5,358 ng/mL, P < 0.0001). Female case and early-onset case (age at diagnosis <52 years) subjects had a steeper decline than control subjects (slope difference −1.1% per year, P = 0.001 in females, −1.6% per year in early-onset case subjects, P = 0.034). In men, adiponectin slopes for case and noncase subjects were parallel. The slope differences by diabetes onset were largely attenuated after adjustment for changes in obesity, whereas the sex-specific slope differences were independent of obesity.
CONCLUSIONS
Lower adiponectin levels were observed already a decade before the diagnosis of diabetes. The marked sex difference in trajectories suggests that sex-specific mechanisms affect the association between adiponectin levels and diabetes development.
doi:10.2337/dc11-2263
PMCID: PMC3507593  PMID: 22933430
14.  Depression-Related Work Disability: Socioeconomic Inequalities in Onset, Duration and Recurrence 
PLoS ONE  2013;8(11):e79855.
Objective
Depression is a major cause of disability in working populations and the reduction of socioeconomic inequalities in disability is an important public health challenge. We examined work disability due to depression with four indicators of socioeconomic status.
Methods
A prospective cohort study of 125 355 Finnish public sector employees was linked to national register data on work disability (>9 days) due to depressive disorders (International Classification of Diseases, codes F32–F34) from January 2005 to December 2011. Primary outcomes were the onset of work disability due to depressive disorders and, among those with such disability, return to work after and recurrent episodes of work disability due to depression.
Results
We found a consistent inverse socioeconomic gradient in work disability due to depression. Lower occupational position, lower educational level, smaller residence size, and rented (vs. owner-occupied) residence were all associated with an increased risk of work disability. Return to work was slower for employees with basic education (cumulative odds ratio = 1.21, 95% CI: 1.05–1.39) compared to those with higher education. Recurrent work disability episodes due to depression were less common among upper-grade non-manual workers (the highest occupational group) than among lower-grade non-manual (hazard ratio = 1.16, 95% CI: 1.07–1.25) and manual (hazard ratio = 1.14, 95% CI: 1.02–1.26) workers.
Conclusions
These data from Finnish public sector employees show persistent socioeconomic inequalities in work disability due to depression from 2005 to 2011 in terms of onset, recovery and recurrence.
doi:10.1371/journal.pone.0079855
PMCID: PMC3835932  PMID: 24278194
15.  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
16.  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
17.  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
18.  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
19.  Obesity and Occupational Injury: A Prospective Cohort Study of 69,515 Public Sector Employees 
PLoS ONE  2013;8(10):e77178.
Background
Obesity and overweight are suggested to increase the risk of occupational injury but longitudinal evidence to confirm this is rare. We sought to evaluate obesity and overweight as risk factors for occupational injuries.
Methodology/Principal Findings
A total of 69,515 public sector employees (80% women) responded to a survey in 2000–2002, 2004 or 2008. Body mass index (kg/m2) was derived from self-reported height and weight and was linked to records of subsequent occupational injuries obtained from national registers. Different injury types, locations and events or exposures (the manner in which the injury was produced or inflicted) were analyzed by body mass index category adjusting for baseline socio-demographic characteristics, work characteristics, health-risk behaviors, physical and mental health, insomnia symptoms, and sleep duration. During the mean follow-up of 7.8 years (SD = 3.2), 18% of the employees (N = 12,204) recorded at least one occupational injury. Obesity was associated with a higher overall risk of occupational injury; multivariable adjusted hazard ratio (HR) 1.21 (95% CI 1.14–1.27). A relationship was observed for bone fractures (HR = 1.37; 95% CI: 1.10–1.70), dislocations, sprains and strains (HR = 1.36; 95% CI: 1.25–1.49), concussions and internal injuries (HR = 1.26; 95% CI: 1.11–1.44), injuries to lower extremities (HR = 1.62; 95%: 1.46–1.79) and injuries to whole body or multiple sites (HR = 1.37; 95%: 1.10–1.70). Furthermore, obesity was associated with a higher risk of injuries caused by slipping, tripping, stumbling and falling (HR = 1.55; 95% CI: 1.40–1.73), sudden body movement with or without physical stress (HR = 1.24; 95% CI: 1.10–1.41) and shock, fright, violence, aggression, threat or unexpected presence (HR = 1.33; 95% CI: 1.03–1.72). The magnitude of the associations between overweight and injuries was smaller, but the associations were generally in the same direction as those of obesity.
Conclusions/Significance
Obese employees record more occupational injuries than those with recommended healthy weight.
doi:10.1371/journal.pone.0077178
PMCID: PMC3797744  PMID: 24146966
20.  Quantifying Policy Options for Reducing Future Coronary Heart Disease Mortality in England: A Modelling Study 
PLoS ONE  2013;8(7):e69935.
Aims
To estimate the number of coronary heart disease (CHD) deaths potentially preventable in England in 2020 comparing four risk factor change scenarios.
Methods and Results
Using 2007 as baseline, the IMPACTSEC model was extended to estimate the potential number of CHD deaths preventable in England in 2020 by age, gender and Index of Multiple Deprivation 2007 quintiles given four risk factor change scenarios: (a) assuming recent trends will continue; (b) assuming optimal but feasible levels already achieved elsewhere; (c) an intermediate point, halfway between current and optimal levels; and (d) assuming plateauing or worsening levels, the worst case scenario. These four scenarios were compared to the baseline scenario with both risk factors and CHD mortality rates remaining at 2007 levels. This would result in approximately 97,000 CHD deaths in 2020. Assuming recent trends will continue would avert approximately 22,640 deaths (95% uncertainty interval: 20,390-24,980). There would be some 39,720 (37,120-41,900) fewer deaths in 2020 with optimal risk factor levels and 22,330 fewer (19,850-24,300) in the intermediate scenario. In the worst case scenario, 16,170 additional deaths (13,880-18,420) would occur. If optimal risk factor levels were achieved, the gap in CHD rates between the most and least deprived areas would halve with falls in systolic blood pressure, physical inactivity and total cholesterol providing the largest contributions to mortality gains.
Conclusions
CHD mortality reductions of up to 45%, accompanied by significant reductions in area deprivation mortality disparities, would be possible by implementing optimal preventive policies.
doi:10.1371/journal.pone.0069935
PMCID: PMC3723729  PMID: 23936122
21.  Risk Models to Predict Hypertension: A Systematic Review 
PLoS ONE  2013;8(7):e67370.
Background
As well as being a risk factor for cardiovascular disease, hypertension is also a health condition in its own right. Risk prediction models may be of value in identifying those individuals at risk of developing hypertension who are likely to benefit most from interventions.
Methods and Findings
To synthesize existing evidence on the performance of these models, we searched MEDLINE and EMBASE; examined bibliographies of retrieved articles; contacted experts in the field; and searched our own files. Dual review of identified studies was conducted. Included studies had to report on the development, validation, or impact analysis of a hypertension risk prediction model. For each publication, information was extracted on study design and characteristics, predictors, model discrimination, calibration and reclassification ability, validation and impact analysis. Eleven studies reporting on 15 different hypertension prediction risk models were identified. Age, sex, body mass index, diabetes status, and blood pressure variables were the most common predictor variables included in models. Most risk models had acceptable-to-good discriminatory ability (C-statistic>0.70) in the derivation sample. Calibration was less commonly assessed, but overall acceptable. Two hypertension risk models, the Framingham and Hopkins, have been externally validated, displaying acceptable-to-good discrimination, and C-statistic ranging from 0.71 to 0.81. Lack of individual-level data precluded analyses of the risk models in subgroups.
Conclusions
The discrimination ability of existing hypertension risk prediction tools is acceptable, but the impact of using these tools on prescriptions and outcomes of hypertension prevention is unclear.
doi:10.1371/journal.pone.0067370
PMCID: PMC3702558  PMID: 23861760
22.  Association of Lifecourse Socioeconomic Status with Chronic Inflammation and Type 2 Diabetes Risk: The Whitehall II Prospective Cohort Study 
PLoS Medicine  2013;10(7):e1001479.
Silvia Stringhini and colleagues followed a group of British civil servants over 18 years to look for links between socioeconomic status and health.
Please see later in the article for the Editors' Summary
Background
Socioeconomic adversity in early life has been hypothesized to “program” a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation.
Methods and Findings
We use data from the British Whitehall II study, a prospective occupational cohort of adults established in 1985. The inflammatory markers C-reactive protein and interleukin-6 were measured repeatedly and type 2 diabetes incidence (new cases) was monitored over an 18-year follow-up (from 1991–1993 until 2007–2009). Our analytical sample consisted of 6,387 non-diabetic participants (1,818 women), of whom 731 (207 women) developed type 2 diabetes over the follow-up. Cumulative exposure to low socioeconomic status from childhood to middle age was associated with an increased risk of developing type 2 diabetes in adulthood (hazard ratio [HR] = 1.96, 95% confidence interval: 1.48–2.58 for low cumulative lifecourse socioeconomic score and HR = 1.55, 95% confidence interval: 1.26–1.91 for low-low socioeconomic trajectory). 25% of the excess risk associated with cumulative socioeconomic adversity across the lifecourse and 32% of the excess risk associated with low-low socioeconomic trajectory was attributable to chronically elevated inflammation (95% confidence intervals 16%–58%).
Conclusions
In the present study, chronic inflammation explained a substantial part of the association between lifecourse socioeconomic disadvantage and type 2 diabetes. Further studies should be performed to confirm these findings in population-based samples, as the Whitehall II cohort is not representative of the general population, and to examine the extent to which social inequalities attributable to chronic inflammation are reversible.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 350 million people have diabetes, a metabolic disorder characterized by high amounts of glucose (sugar) in the blood. Blood sugar levels are normally controlled by insulin, a hormone released by the pancreas after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes) blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes, which was previously called adult-onset diabetes, can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. However, as the disease progresses, the pancreatic beta cells, which make insulin, become impaired and patients may eventually need insulin injections. Long-term complications, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
Socioeconomic adversity in childhood seems to increase the risk of developing type 2 diabetes but why? One possibility is that chronic inflammation mediates the association between socioeconomic adversity and type 2 diabetes. Inflammation, which is the body's normal response to injury and disease, affects insulin signaling and increases beta-cell death, and markers of inflammation such as raised blood levels of C-reactive protein and interleukin 6 are associated with future diabetes risk. Notably, socioeconomic adversity in early life leads to exaggerated inflammatory responses later in life and people exposed to social adversity in adulthood show greater levels of inflammation than people with a higher socioeconomic status. In this prospective cohort study (an investigation that records the baseline characteristics of a group of people and then follows them to see who develops specific conditions), the researchers test the hypothesis that chronically increased inflammatory activity in individuals exposed to socioeconomic adversity over their lifetime may partly mediate the association between socioeconomic status over the lifecourse and future type 2 diabetes risk.
What Did the Researchers Do and Find?
To assess the extent to which chronic inflammation explains the association between lifecourse socioeconomic status and type 2 diabetes incidence (new cases), the researchers used data from the Whitehall II study, a prospective occupational cohort study initiated in 1985 to investigate the mechanisms underlying previously observed socioeconomic inequalities in disease. Whitehall II enrolled more than 10,000 London-based government employees ranging from clerical/support staff to administrative officials and monitored inflammatory marker levels and type 2 diabetes incidence in the study participants from 1991–1993 until 2007–2009. Of 6,387 participants who were not diabetic in 1991–1993, 731 developed diabetes during the 18-year follow-up. Compared to participants with the highest cumulative lifecourse socioeconomic score (calculated using information on father's occupational position and the participant's educational attainment and occupational position), participants with the lowest score had almost double the risk of developing diabetes during follow-up. Low lifetime socioeconomic status trajectories (being socially downwardly mobile or starting and ending with a low socioeconomic status) were also associated with an increased risk of developing diabetes in adulthood. A quarter of the excess risk associated with cumulative socioeconomic adversity and nearly a third of the excess risk associated with low socioeconomic trajectory was attributable to chronically increased inflammation.
What Do These Findings Mean?
These findings show a robust association between adverse socioeconomic circumstances over the lifecourse of the Whitehall II study participants and the risk of type 2 diabetes and suggest that chronic inflammation explains up to a third of this association. The accuracy of these findings may be affected by the measures of socioeconomic status used in the study. Moreover, because the study participants were from an occupational cohort, these findings need to be confirmed in a general population. Studies are also needed to examine the extent to which social inequalities in diabetes risk that are attributable to chronic inflammation are reversible. Importantly, if future studies confirm and extend the findings reported here, it might be possible to reduce the social inequalities in type 2 diabetes by promoting interventions designed to reduce inflammation, including weight management, physical activity, and smoking cessation programs and the use of anti-inflammatory drugs, among socially disadvantaged groups.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001479.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes; it includes peoples stories about diabetes
The nonprofit Diabetes UK also provides detailed information about diabetes for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the nonprofit Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
Information about the Whitehall II study is available
doi:10.1371/journal.pmed.1001479
PMCID: PMC3699448  PMID: 23843750
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.  Workplace Determinants of Social Capital: Cross-Sectional and Longitudinal Evidence from a Finnish Cohort Study 
PLoS ONE  2013;8(6):e65846.
Objective
To examine which contextual features of the workplace are associated with social capital.
Methods
This is a cohort study of 43,167 employees in 3090 Finnish public sector workplaces who responded to a survey of individual workplace social capital in 2000–02 (response rate 68%). We used ecometrics approach to estimate social capital of work units. Features of the workplace were work unit's demographic and employment patterns and size, obtained from employers' administrative records. We used multilevel-multinomial logistic regression models to examine cross-sectionally whether these features were associated with social capital between individuals and work units. Fixed effects models were used for longitudinal analyses in a subsample of 12,108 individuals to examine the effects of changes in workplace characteristics on changes in social capital between 2000 and 2004.
Results
After adjustment for individual characteristics, an increase in work unit size reduced the odds of high levels of individual workplace social capital (odds ratio 0.94, 95% confidence interval 0.91–0.98 per 30-person-year increase). A 20% increase in the proportion of manual and male employees reduced the odds of high levels of social capital by 8% and 23%, respectively. A 30% increase in temporary employees and a 20% increase in employee turnover were associated with 11% (95% confidence interval 1.04–1.17) and 24% (95% confidence interval 1.18–1.30) higher odds of having high levels of social capital respectively). Results from fixed effects models within individuals, adjusted for time-varying covariates, and from social capital of the work units yielded consistent results.
Conclusions
These findings suggest that workplace social capital is contextually patterned. Workplace demographic and employment patterns as well as the size of the work unit are important in understanding variations in workplace social capital between individuals and workplaces.
doi:10.1371/journal.pone.0065846
PMCID: PMC3679109  PMID: 23776555
25.  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

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