The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

Adverse childhood experiences and incident coronary heart disease: a counterfactual analysis in the Whitehall II prospective cohort study.

OBJECTIVES: Adverse childhood experience is thought to be associated with risk of coronary heart disease, but it is not clear which experiences are cardiotoxic, and whether risk increases with the accumulation of adverse childhood experiences. METHODS: Participants were 5149 adults (72.6% men) in the Whitehall II cohort study. Parental death was recorded at phase 1 (median age in years 44.3), and 13 other adverse childhood experiences at phase 5 (55.3). We applied Cox proportional hazards regression with person-time from phase 5 to examine associations of adverse childhood experiences with incident coronary heart disease. We predicted hazard ratios according to count of the experiences, and examined dose-response effect. We finally estimated reduction of coronary heart disease in a hypothetical scenario, the absence of adverse childhood experiences. RESULTS: Among study participants, 62.9% had at least one adversity, with "financial problems" having the highest prevalence (26.1%). There were 509 first episodes of coronary heart disease during an average 12.9 years follow-up. Among 14 adverse childhood experiences in a multiply adjusted model, "parental unemployment" showed the highest hazard of coronary heart disease incidence (hazard ratio; 95% confidence interval: 1.53; 1.16 to 2.02). No dose-response effect was observed (constant for proportionality in hazard ratio: 1.05, 0.99 to 1.11). Based on the estimates of final model, in the absence of childhood adversities, we estimated a 6.0% reduction in coronary heart disease (0.94; 0.87 to 1.01), but the confidence interval includes one. CONCLUSION: Although individual adverse childhood experiences show some association with coronary heart disease, there is no clear relationship with the number of adverse experiences. Further research is required to quantify effects of multiple and combinations of adverse childhood experiences considering timing, duration, and severity.

Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses.

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2). CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.

Diurnal pattern of salivary cortisol and progression of aortic stiffness: Longitudinal study.

BACKGROUND: The positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized. However, the link between hypothalamic-pituitary-adrenal (HPA) dysregulation and subclinical cardiovascular disease has not been studied longitudinally. We investigated the relation of diurnal salivary cortisol, as a biological marker of stress levels, with progression of aortic stiffness over five years. METHODS: A total of 3281 people (mean age 65.5) in the Whitehall II prospective study provided six saliva samples on a single weekday. We assessed the diurnal salivary cortisol using the daytime slope and bedtime level. Aortic stiffness was measured by carotid-femoral pulse wave velocity (PWV) at baseline (2007-2009) and five years later (2012-2013). Linear mixed models were used to estimate the association of diurnal salivary cortisol with baseline PWV and five-year longitudinal changes. RESULTS: Diurnal salivary cortisol were not associated with PWV at baseline. Among women but not men, a 1-SD shallower salivary cortisol slope at baseline was associated with a five-year increase in PWV (ß = 0.199; 95% CI = 0.040, 0.358 m/s) and higher bedtime cortisol level (ß = 0.208, 95% CI = 0.062, 0.354 m/s). CONCLUSIONS: Dysregulation of the HPA axis measured using salivary cortisol (shallower slope, higher bedtime level) predicted the rate of progression of aortic stiffness among women.

Why is living alone in older age related to increased mortality risk? A longitudinal cohort study.

BACKGROUND: Living alone has been associated with increased mortality risk, but it is unclear whether this is a result of a selection effect or the impact of stressful life changes such as widowhood or divorce leading to changes in living arrangements. We therefore examined the association between living alone, transitions in living arrangements and all-cause mortality. METHOD: We analysed data from 4,888 individuals who participated in both wave 2 (2004-2005) and wave 4 (2008-2009) of the English Longitudinal Study of Ageing. Transitions in living arrangements over this period were identified. Mortality status was ascertained from linked national mortality registers. Cox proportional hazards analysis was used to examine the association between living alone and mortality over an average 8.5 year follow-up period. RESULTS: An association was found between living alone at wave 4 and mortality (hazard ratio (HR): 1.20, 95% CI 1.04-1.38) in a model adjusted for multiple factors including socioeconomic status, physical health, health behaviours and loneliness. We also found that participants who moved to living alone after divorce or bereavement had a higher risk of mortality compared with those who lived with others at both time points (HR: 1.34, 95% CI 1.01-1.79), while those who moved to living alone for other reasons did not show an increased mortality risk. CONCLUSIONS: The relationship between living alone and mortality is complicated by the reasons underlying not living with others. A greater understanding of these dynamics will help to identify the individuals who are at particular health risk because of their living arrangements.

Risk Factors for Hospital Admission After a Fall: A Prospective Cohort Study of Community-Dwelling Older People.

BACKGROUND: Falls in later life that require admission to hospital have well-established consequences for future disability and health. The likelihood and severity of a fall will result from the presence of one or more risk factors. The aim of this study is to examine risk factors identified for their ability to prevent falls and to assess whether they are associated with hospital admission after a fall. METHODS: Analyses of data from the English Longitudinal Study of Aging (ELSA), a prospective cohort study. In a sample of 3783 men and women older than 60 years old, a range of potential risk factors measured at Wave 4 (demographic, social environment, physical, and mental functioning) were examined as predictors of fall-related hospitalizations, identified using International Classification of Diseases, 10th Revision (ICD-10) code from linked hospital records in the United Kingdom. Subdistribution hazard models were used to account for competing risk of death. RESULTS: Several risk factors identified by previous work were confirmed. Suffering from urinary incontinence (subdistribution hazard ratio = 1.49; 95% CI: 1.14, 1.95) and osteoporosis (subdistribution hazard ratio = 1.48; 95% CI: 1.05, 2.07), which are not commonly considered at an early stage of screening, were found to be associated with hospital admission after a fall. Both low and moderate levels of physical activity were also found to somewhat increase the risk of hospital admission after a fall. CONCLUSIONS: Several predictors of having a fall, severe enough to require hospital admission, have been confirmed. In particular, urinary incontinence should be considered at an earlier point in the assessment of risk.

A longitudinal analysis of loneliness, social isolation and falls amongst older people in England.

Loneliness and social isolation have been identified as important predictors of various health outcomes, but little research has investigated their influence on falls. This study aimed to investigate the longitudinal association between loneliness, social isolation and falls amongst older adults in England, looking at both self-reported falls and falls that require hospital admissions. This study drew on large scale, nationally representative data from the English Longitudinal Study of Ageing linked with Hospital Episode Statistics. Data were analysed using survival analysis, with self-reported falls (total sample = 4013) and falls require hospital admission being modelled separately (total sample = 9285). There was a 5% increase in the hazard of self-reported falls relative to one point increase in loneliness independent of socio-demographic factors (HR: 1.05, 95% CI: 1.02-1.08), but the association was explained away by individual differences in health and life-style measures (HR: 1.03, 95% CI: 1.00-1.07). Both living alone (HR: 1.18, 95% CI: 1.07-1.32) and low social contact (HR: 1.04, 95% CI: 1.01-1.07) were associated with a greater hazard of self-reported falls even after controlling for socio-demographic, health and life-style differences. Similar results were also found for hospital admissions following a fall. Our findings were robust to a variety of model specifications.

Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study.

BACKGROUND: Health inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures. METHODS: In this multi-wave longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45-55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years [SD 5·9]). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data. FINDINGS: Between Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model. INTERPRETATION: Behavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty. FUNDING: British Heart Foundation and British Medical Research Council.

Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension.

Aims: To examine associations of diastolic and systolic blood pressure (SBP) at age 50, 60, and 70 years with incidence of dementia, and whether cardiovascular disease (CVD) over the follow-up mediates this association. Methods and results: Systolic and diastolic blood pressure were measured on 8639 persons (32.5% women) from the Whitehall II cohort study in 1985, 1991, 1997, and 2003. Incidence of dementia (n dementia/n total = 385/8639) was ascertained from electronic health records followed-up until 2017. Cubic splines using continuous blood pressure measures suggested SBP ≥130 mmHg at age 50 but not at age 60 or 70 was associated with increased risk of dementia, confirmed in Cox regression analyses adjusted for sociodemographic factors, health behaviours, and time varying chronic conditions [hazard ratio (HR) 1.38; 95% confidence interval (95% CI) 1.11, 1.70]. Diastolic blood pressure was not associated with dementia. Participants with longer exposure to hypertension (SBP ≥ 130 mmHg) between mean ages of 45 and 61 years had an increased risk of dementia compared to those with no or low exposure to hypertension (HR 1.29, 95% CI 1.00, 1.66). In multi-state models, SBP ≥ 130 mmHg at 50 years of age was associated with greater risk of dementia in those free of CVD over the follow-up (HR 1.47, 95% CI 1.15, 1.87). Conclusion: Systolic blood pressure ≥130 mmHg at age 50, below the conventional ≥140 mmHg threshold used to define hypertension, is associated with increased risk of dementia; in these persons this excess risk is independent of CVD.

Parental absence in early childhood and onset of smoking and alcohol consumption before adolescence.

BACKGROUND: Parental absence, due to death or separation from a parent, has been associated with smoking and alcohol consumption in adolescence and adulthood. The aim of this study was to investigate whether parental absence in early childhood was associated with smoking and alcohol uptake before adolescence. METHODS: Data on 10 940 children from the UK's Millennium Cohort Study were used. Logistic regression was used to test associations between parental absence (0-7 years) and reports of smoking and alcohol consumption at age 11. RESULTS: Children who experienced parental absence were more likely to have smoked (OR=2.58, 95% CI 1.88 to 3.56) and consumed alcohol (OR=1.46, 95% CI 1.25 to 1.72). No differences were found by child sex or age, or parent absent. Children who experienced parental death were less likely to have drunk alcohol but those who had were more likely to have consumed enough to feel drunk. CONCLUSIONS: Parental absence was associated with early uptake of risky health behaviours in a large, nationally representative UK cohort. Children who experience parental absence should be supported in early life in order to prevent smoking and alcohol initiation.

Crossing the road in time: Inequalities in older people's walking speeds.

Pedestrian crossings in the UK and US require people to walk at 1.2 m/s to cross the road in time; however a large proportion of older people do not walk this fast, potentially discouraging walking or putting older people at risk of injury. We use longitudinal data to investigate changes in walking speed, and ability to cross the road in time, at older ages. 31,015 walking speed measurements were taken from 10,249 men and women aged 60+ years in waves 1-7 of the English Longitudinal Study of Ageing (2002-2014). Growth curve analyses were used to model how walking speed changes with increasing age, and predicted probabilities of being able to cross the road in time were estimated. 10% of measured walking speeds were fast enough to cross the road in time. Walking speed declined with age (-5.7×10-3m/s/yr (95% CI -7.6×10-3, -3.9×10-3)), and the decline accelerated with increasing age (-0.3 ×10-3m/s/yr (-0.4 ×10-3, -0.3 ×10-3)). Female, less wealthy and less healthy older people had slower walking speeds. For instance, predicted probability of crossing the road in time at age 60 was 14.8% (10.1, 18.5) and 2.7% (1.5, 3.8) for the richest and poorest men and 8.4% (6.0, 1.1) and 1.5% (0.9, 2.2) for the richest and poorest women, and at age 80 they were 7.1% (3.6, 10.5) and 1.0% (0.3, 1.7) for the richest and poorest men and 3.7% (1.6, 5.9) and 0.5% (0.1, 0.9) for the richest and poorest women. Most older people do not walk fast enough to cross the road in time. Even the majority of the wealthiest and healthiest people aged 60 years and older do not walk fast enough to cross pedestrian crossings in the allocated time. Crossing times should be increased to allow for older peoples' slower walking speeds or other policies considered to improve walkability, and to help avoid injuries and social isolation.

Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study.

Objective To test the hypotheses that physical activity in midlife is not associated with a reduced risk of dementia and that the preclinical phase of dementia is characterised by a decline in physical activity.Design Prospective cohort study with a mean follow-up of 27 years.Setting Civil service departments in London (Whitehall II study).Participants 10 308 participants aged 35-55 years at study inception (1985-88). Exposures included time spent in mild, moderate to vigorous, and total physical activity assessed seven times between 1985 and 2013 and categorised as "recommended" if duration of moderate to vigorous physical activity was 2.5 hours/week or more.Main outcome measures A battery of cognitive tests was administered up to four times from 1997 to 2013, and incident dementia cases (n=329) were identified through linkage to hospital, mental health services, and mortality registers until 2015.Results Mixed effects models showed no association between physical activity and subsequent 15 year cognitive decline. Similarly, Cox regression showed no association between physical activity and risk of dementia over an average 27 year follow-up (hazard ratio in the "recommended" physical activity category 1.00, 95% confidence interval 0.80 to 1.24). For trajectories of hours/week of total, mild, and moderate to vigorous physical activity in people with dementia compared with those without dementia (all others), no differences were observed between 28 and 10 years before diagnosis of dementia. However, physical activity in people with dementia began to decline up to nine years before diagnosis (difference in moderate to vigorous physical activity -0.39 hours/week; P=0.05), and the difference became more pronounced (-1.03 hours/week; P=0.005) at diagnosis.Conclusion This study found no evidence of a neuroprotective effect of physical activity. Previous findings showing a lower risk of dementia in physically active people may be attributable to reverse causation-that is, due to a decline in physical activity levels in the preclinical phase of dementia.

Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year Follow-up Study.

Importance: Neuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate. Objective: To characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia. Design, Setting, and Participants: Up to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015. Data analysis for this study in a UK general community was conducted from October to December 2016. Exposures: Depressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire. Main Outcomes and Measures: Incidence of dementia (n = 322) between 1985 and 2015. Results: Of the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, those with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared with those without dementia became apparent 11 years (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 5.81; 95% CI, 4.81-6.81; P < .001). Conclusions and Relevance: Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia. Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes. The findings do not support the hypothesis that depressive symptoms increase the risk for dementia.

Assessing cortisol from hair samples in a large observational cohort: The Whitehall II study.

Hair cortisol concentrations (HCC) have been suggested to reflect long-term integrated cortisol levels, but most evidence of associations with co-variates is from small samples of healthy volunteers. The objective of this study was to describe the collection of hair samples in a large cohort study and report associations of demographic and health measures with HCC. We examined HCC measured from the 3cm hair segment near the scalp in 3507 participants (aged 59-83y) from The Whitehall II occupational cohort study of British civil servants. Hair samples were analysed using a column switching LC-APCI-MS/MS assay. Findings from mutually adjusted linear regression analyses revealed lower HCC in participants who reported use of hair dye [% difference (95%CI); -12.5 (-22.0, -1.9), p value=0.022] and evidence suggestive of differences by length of sample storage and seasonal variation. With regard to demographic variables, HCC was lower in women compared to men [-17.0 (-24.8, -8.4), p value <0.001] and higher in Black compared to other ethnic groups. Prevalent diabetes, use of systemic corticosteroids and cardiovascular medication were independently associated with higher HCC. With regard to health, depressive symptoms were associated with higher HCC [20.0 (8.1, 33.3), p value=0.001] following adjustment for physical disease and medication. We conclude that hair steroid analysis presents significant opportunities for assessing cortisol in large scale cohorts. Demographic factors, sample storage, season of collection and hair characteristics should be considered in future analyses. Health status, both mental and physical, is linked to HCC.

Recurrent short sleep, chronic insomnia symptoms and salivary cortisol: A 10-year follow-up in the Whitehall II study.

Although an association between both sleep duration and disturbance with salivary cortisol has been suggested, little is known about the long term effects of poor quality sleep on diurnal cortisol rhythm. The aim of this study was to examine the association of poor quality sleep, categorised as recurrent short sleep duration and chronic insomnia symptoms, with the diurnal release of cortisol. We examined this in 3314 participants from an occupational cohort, originally recruited in 1985-1989. Salivary cortisol was measured in 2007-2009 and six saliva samples were collected: (1) waking, (2) waking+0.5h, (3) +2.5h, (4) +8h, (5) +12h and (6) bedtime, for assessment of the cortisol awakening response and the diurnal slope in cortisol secretion. Participants with the first saliva sample collected within 15min of waking and not on steroid medication were examined. Short sleep duration (≤5h) and insomnia symptoms (Jenkins scale, highest quartile) were measured in 1997-1999, 2003-2004 and 2007-2009. Recurrent short sleep was associated with a flatter diurnal cortisol pattern. A steeper morning rise in cortisol was observed among those reporting chronic insomnia symptoms at three time points and among those reporting short sleep twice, compared to those who never reported sleep problems. Participants reporting short sleep on three occasions had higher levels of cortisol later in the day, compared to those never reporting short sleep, indicated by a positive interaction with hours since waking (ß=0.02 (95% CI: 0.01, 0.03)). We conclude that recurrent sleep problems are associated with adverse salivary cortisol patterns throughout the day.