Post-menopausal women exhibit greater interleukin-6 responses to mental stress than older men

Background Acute stress triggers innate immune responses and elevation in circulating cytokines including interleukin-6 (IL-6). The effect of sex on IL-6 responses remains unclear due to important limitations of previous studies. Purpose The purpose of this study was to examine sex differences in IL-6 responses to mental stress in a healthy, older (post-menopausal) sample accounting for several moderating factors. Methods Five hundred six participants (62.9 ± 5.60 years, 55 % male) underwent 10 min of mental stress consisting of mirror tracing and Stroop task. Blood was sampled at baseline, after stress, and 45 and 75 min post-stress, and assayed using a high sensitivity kit. IL-6 reactivity was computed as the mean difference between baseline and 45 min and between baseline and 75 min post-stress. Main effects and interactions were examined using ANCOVA models. Results There was a main effect of time for the IL-6 response (F 3,1512 = 201.57, p = <.0001) and a sex by time interaction (F 3,1512 = 17.07, p = <.001). In multivariate adjusted analyses, IL-6 reactivity was significantly greater in females at 45 min (M = 0.37 ± 0.04 vs. 0.20 ± 0.03 pg/mL, p = .01) and at 75 min (M = 0.57 ± 0.05 vs. 0.31 ± 0.05 pg/mL, p = .004) post-stress compared to males. Results were independent of age, adiposity, socioeconomic position, depression, smoking and alcohol consumption, physical activity, statin use, testing time, task appraisals, hormone replacement, and baseline IL-6. Other significant predictors of IL-6 reactivity were lower household wealth, afternoon testing, and baseline IL-6. Conclusions Healthy, post-menopausal females exhibit substantially greater IL-6 responses to acute stress. Inflammatory responses if sustained over time may have clinical implications for the development and maintenance of inflammatory-related conditions prevalent in older women

Effects of substituting sedentary time with physical activity on metabolic risk

Purpose: The detrimental effects of sedentary time on health may act by replacing time spent in physical activities. The aim of this study was to examine cross-sectional associations between objectively assessed sedentary and physical activity domains and cardiometabolic risk factors using a novel isotemporal substitution paradigm. Methods: Participants were 445 healthy men and women (mean age, 66 ± 6 yr), without history or objective signs of cardiovascular disease, drawn from the Whitehall II epidemiological cohort. Physical activity was objectively measured using accelerometers (ActiGraph GT3X) worn around the waist during waking hours for 4–7 consecutive days. We examined the effects of replacing sedentary time with light activity or moderate-to-vigorous physical activity (MVPA) on a range of risk factors (HDL cholesterol, triglycerides, HbA1c, and body mass index) using an isotemporal substitution paradigm. Results: In partition models, where the time in each of the intensity categories was held constant, only MVPA remained associated with risk factors. In isotemporal substitution models that held total (wear) time constant, replacing 10-min sedentary time with an equal amount of MVPA was associated with favorable effects in all risk factors, including HbA1c (B = −0.023; 95% confidence interval (CI), −0.043 to −0.002), BMI (B = −0.39; 95% CI, −0.54 to −0.24), HDL cholesterol (B = 0.037; 95% CI, 0.021–0.054), and triglycerides (B = −0.035; 95% CI, −0.061 to −0.009). Conclusions: The associations between sedentary behavior and cardiometabolic risk may be dependent on the types of activities that are displaced by sedentary time

Longitudinal patterns in physical activity and sedentary behaviour from mid-life to early old age: a substudy of the Whitehall II cohort

Background There are few longitudinal data on physical activity patterns from mid-life into older age. The authors examined associations of self-reported physical activity, adiposity and socio-demographic factors in mid-life with objectively assessed measures of activity in older age. Methods Participants were 394 healthy men and women drawn from the Whitehall II population-based cohort study. At the baseline assessment in 1997 (mean age 54 years), physical activity was assessed through self-report and quantified as metabolic equivalent of task hours/week. At the follow-up in 2010 (mean age 66 years), physical activity was objectively measured using accelerometers worn during waking hours for seven consecutive days (average daily wear time 891668 min/day). Results Self-reported physical activity at baseline was associated with objectively assessed activity at follow-up in various activity categories, including light-, moderate and vigorous-intensity activity (all ps<0.04). Participants in the highest compared with lowest quartile of self reported activity level at baseline recorded on average 64.1 (95% CI 26.2 to 102.1) counts per minute more accelerometer-assessed activity at follow-up and 9.0 (2.0e16.0) min/day more moderate-to-vigorous daily activity, after adjusting for baseline covariates. Lower education, obesity and self-perceived health status were also related to physical activity at follow-up. Only age and education were associated with objectively measured sedentary time at follow-up. Conclusion Physical activity behaviour in middle age was associated with objectively measured physical activity in later life after 13 years of follow-up, suggesting that the habits in adulthood are partly tracked into older age

The effect of experimentally induced sedentariness on mood and psychobiological responses to mental stress.

Background Evidence suggests a link between sedentary behaviours and depressive symptoms. Mechanisms underlying this relationship are not understood, but inflammatory processes may be involved. Autonomic and inflammatory responses to stress may be heightened in sedentary individuals contributing to risk, but no study has experimentally investigated this. Aim To examine the effect of sedentary time on mood and stress responses using an experimental design. Method Forty-three individuals were assigned to a free-living sedentary condition and to a control condition (usual activity) in a cross-over, randomised fashion and were tested in a psychophysiology laboratory after spending 2 weeks in each condition. Participants completed mood questionnaires (General Health Questionnaire and Profile of Mood States) and wore a motion sensor for 4 weeks. Results Sedentary time increased by an average of 32 min/day (P = 0.01) during the experimental condition compared with control. Being sedentary resulted in increases in negative mood independent of changes in moderate to vigorous physical activity (ΔGHQ = 6.23, ΔPOMS = 2.80). Mood disturbances were associated with greater stress-induced inflammatory interleukin-6 (IL-6) responses (β = 0.37). Conclusion Two weeks of exposure to greater free-living sedentary time resulted in mood disturbances independent of reduction in physical activity. Stress-induced IL-6 responses were associated with changes in mood

Decreased reaction time variability is associated with greater cardiovascular responses to acute stress

Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75-min recovery. RT measures were generated from an ex-Gaussian distribution that yielded three predictors: mu-RT, sigma-RT, and tau-RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = −.009, SE = .005, p = .09) and diastolic (B = −.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = −.007, SE = .003, p = .03) and impaired vagal tone (B = −.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses

Socioeconomic status and central adiposity as determinants of stress-related biological responses relevant to cardiovascular disease risk

Stress-related processes have been implicated in the associations between lower socioeconomic status (SES), central adiposity, and cardiovascular disease risk. This study analysed the impact of SES and central adiposity on cardiovascular, inflammatory and neuroendocrine stress responses, and associations with cytomegalovirus (CMV) infection in a sample of 537 men and women aged 53-76 years (mean 62.89 years). SES was defined by grade of employment (higher, intermediate, and lower categories), and central adiposity was indexed by waist-hip ratio (WHR). Cardiovascular, inflammatory and cortisol responses were monitored during administration of a standardized mental stress testing protocol and salivary cortisol was measured repeatedly over the day. Lower SES was associated with raised systolic and diastolic blood pressure (BP), plasma interleukin (IL-6), fibrinogen, C-reactive protein, and salivary cortisol, and a large WHR accentuated SES differences in fibrinogen, C-reactive protein, and likelihood of CMV seropositivity, independently of general adiposity indexed by body mass index. During mental stress testing, return to resting levels (recovery) following behavioural challenge in systolic and diastolic BP and heart rate was impaired among lower SES participants, particularly those with large WHR. Lower SES participants had greater cortisol concentrations across the day, but this pattern did not vary with WHR. These findings extend the evidence relating lower SES to stress-related biological risk factors for cardiovascular disease, and indicate that central adiposity may augment these effects

The combined association of psychological distress and socioeconomic status with all-cause mortality: a national cohort study.

Background Psychological distress and low socioeconomic status (SES) are recognized risk factors for mortality. The aim of this study was to test whether lower SES amplifies the effect of psychological distress on all-cause mortality. Methods We selected 66 518 participants from the Health Survey for England who were 35 years or older, free of cancer and cardiovascular disease at baseline, and living in private households in England from 1994 to 2004. Selection used stratified random sampling, and participants were linked prospectively to mortality records from the Office of National Statistics (mean follow-up, 8.2 years). Psychological distress was measured using the 12-item General Health Questionnaire, and SES was indexed by occupational class. Results The crude incidence rate of death was 14.49 (95% CI, 14.17-14.81) per 1000 person-years. After adjustment for age and sex, psychological distress and low SES category were associated with increased mortality rates. In a stratified analysis, the association of psychological distress with mortality differed with SES (likelihood ratio test–adjusted P < .001), with the strongest associations being observed in the lowest SES categories. Conclusions The detrimental effect of psychological distress on mortality is amplified by low SES category. People in higher SES categories have lower mortality rates even when they report high levels of psychological distress. Psychological distress is becoming recognized increasingly as a risk factor for mortality and a trigger for cardiovascular disease (CVD) events.1- 3 Socioeconomic status (SES) is also a recognized determinant of health status: in developed countries, lower SES levels signal worse health. Even in the most affluent countries, people in lower SES levels have considerably shorter life expectancies and more disease than people in higher SES levels,4- 6 and low SES levels are associated with a high risk for CVD and death in developed countries, such as England.7 People in higher SES categories may have greater economic, social, and psychological resources and better coping strategies for dealing with adversity.8 These assets may be acquired through learning or better access to resources. Consequently, when both risk factors are present (high levels of psychological distress and low SES levels), we can argue that the resulting effect on mortality is not the mere sum of the two (additive effect) but that some extra risk may appear (multiplicative effect). We therefore hypothesized that SES can operate as an amplifier of psychological distress and that the effect of psychological distress on mortality would be greater in groups with lower compared with higher SES levels. As a consequence, vulnerable populations of adults may be more susceptible to the detrimental effects of psychological distress and may have unmet health care needs. Identifying people who are more vulnerable to the health consequences of psychological distress may have clinical and public health implications. For example, questionnaires such as the 12-item General Health Questionnaire (GHQ-12) could be of value in systematic screening by family physicians with the aim of improving the recognition rate of common mental disorders and thereby reducing the risk for CVD and other fatal conditions. We sought to analyze the association of psychological distress and low SES levels on the incidence of all-cause mortality, with an emphasis on the interaction between both risk factors

The longitudinal relationship between cortisol responses to mental stress and leukocyte telomere attrition

Context: Chronic psychological stress has been associated with shorter telomeres in some studies, but the underlying mechanisms are poorly understood. One possibility is that the neuroendocrine responses associated with stress exposure are involved. Objective: To testing the hypothesis that greater cortisol responsivity to acute stressors predicts more rapid telomere attrition. Design: We measured salivary cortisol responses to two challenging behavioral tasks. Leukocyte telomere length was measured at the time of mental stress testing and 3 years later. Participants: We studied 411 initially healthy men and women aged 54-76 years. Main outcome measure: Leukocyte telomere length. Results: Cortisol responses to this protocol were small, we divided participants into cortisol responders (n = 156) and non-responders (n = 255) using a criterion (≥20%) previously shown to predict increases in cardiovascular disease risk. There was no significant association between cortisol responsivity and baseline telomere length, although cortisol responders tended to have somewhat shorter telomeres (β = -0.061, standard error 0.049). But cortisol responders had shorter telomeres and more rapid telomere attrition than non-responders on follow-up, after controlling statistically for age, gender, socioeconomic status, smoking, time of day of stress testing and baseline telomere length (β = -0.10, standard error 0.046, p = 0.029). The association was maintained after additional control for cardiovascular risk factors (β = -0.11, p = 0.031). The difference between cortisol responders and non-responders was equivalent to approximately 2 years in aging. Conclusions: These findings suggest that cortisol responsivity may mediate in part the relationship between psychological stress and cellular aging

Short sleep duration is associated with shorter telomere length in healthy men: findings from the Whitehall II cohort study

Background: Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people. Methods: Participants were 434 men and women aged 63.3 years on average drawn from the Whitehall II cohort study. Sleep duration was measured by self-report. Results: There was a linear association between sleep duration and leukocyte telomere length in men but not in women (P = 0.035). Men reporting shorter sleep duration had shorter telomeres, independently of age, body mass index, smoking, educational attainment, current employment, cynical hostility scores and depressive symptoms. Telomeres were on average 6% shorter in men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per night. Conclusion: This study adds to the growing literature relating sleep duration with biomarkers of aging, and suggests that shortening of telomeres might reflect mechanisms through which short sleep contributes to pathological conditions in older men

Effect of short-term weight loss on mental stress-induced cardiovascular and pro-inflammatory responses in women

Epidemiologic evidence links psychosocial stress with obesity but experimental studies examining the mechanisms that mediates the effect of stress on adiposity are scarce. The aim of this study was to investigate whether changes in adiposity following minimal weight loss affect heightened stress responses in women, and examine the role of the adipokine leptin in driving inflammatory responses. Twenty-three overweight or obese, but otherwise healthy, women (M age ¼ 30.41 ± 8.0 years; BMI ¼ 31.9 ± 4.1 kg/m2 ) completed standardized acute mental stress before and after a 9-week calorie restriction program designed to modify adiposity levels. Cardiovascular (blood pressure and heart rate) and inflammatory cytokines (leptin and interleukin-6; IL-6) responses to mental stress were assessed several times between baseline and a 45-min post-stress recovery period. There were modest changes in adiposity measures while the adipokine leptin was markedly reduced (27%) after the intervention. Blood pressure reactivity was attenuated (3.38 ± 1.39 mmHg) and heart rate recovery was improved (2.07 ± 0.96 Bpm) after weight loss. Blood pressure responses were inversely associated with changes in waist to hip ratio post intervention. Decreased levels of circulating leptin following weight loss were inversely associated with the IL-6 inflammatory response to stress (r ¼ 0.47). We offered preliminary evidence suggesting that modest changes in adiposity following a brief caloric restriction program may yield beneficial effect on cardiovascular stress responses. In addition, reductions in basal leptin activity might be important in blunting pro-inflammatory responses. Large randomized trials of the effect of adiposity on autonomic responses are thus warranted