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

Physical activity, adiposity, stress-induced inflammation, and cardiovascular disease risk

Physical inactivity and adiposity are independent risk factors for several chronic conditions including coronary heart disease. Activity and adiposity also modulate psychophysiological responses to psychosocial stress. Since heightened cardiovascular and inflammatory responses to mental stress predict cardiovascular risk, these two factors may influence cardiovascular risk through modulation of autonomic reactivity to stress. However, experimental evidence to support this hypothesis is scarce. The aim of this project is to investigate the associations between physical activity, adiposity, mental stress and mood and physiological reactivity using naturalistic and controlled laboratory methods. Study one examined the association between self-reported physical activity participation, diurnal cortisol rhythm and mood symptoms in everyday life. Study two used an experimental design to examine the effect of physical activity on mood symptoms and on cardiovascular and inflammatory responses to acute mental stress. Exercise withdrawal was used as a model of physical inactivity to induce mood disturbances in healthy, active participants. Several stress-induced markers relevant in cardiovascular disease were examined including pro-inflammatory factors and cortisol. Study three examined the effect of adiposity on physiological responses to acute mental stress and mood. Weight loss was experimentally induced through caloric restriction in overweight or obese women. Responses to acute stress were compared before and after weight loss. Cardiovascular and inflammatory responses to acute stress were evaluated to establish whether adiposity is associated with a heightened or blunted response. The combination of studies presented in this thesis provides insight into the complex relationships that links behavioural factors such as physical activity with mood and stress. An understanding of the mechanisms involved in the association between adiposity, physical activity and cardiovascular risk is invaluable in informing preventive strategies and health related programmes

Cortisol Responses to Mental Stress and the Progression of Coronary Artery Calcification in Healthy Men and Women

Background: Psychosocial stress is a risk factor for coronary heart disease (CHD). The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA) axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC). Methods and Results: Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD) and CAC progression (odds ratio = 1.27, 95% CI, 1.02–1.60) after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85–1.24). Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen. Conclusion: Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD

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 = 30.41 ± 8.0 years; BMI = 31.9 ± 4.1 kg/m(2)) 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 = -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

Correlates of physical activity among community-dwelling adults aged 50 or over in six low- and middle-income countries

Background: Considering that physical activity is associated with healthy ageing and helps to delay, prevent, or manage a plethora of non-communicable diseases in older adults, there is a need to investigate the factors that influence physical activity participation in this population. Thus, we investigated physical activity correlates among community-dwelling older adults (aged ≥50 years) in six low- and middle-income countries. Methods: Cross-sectional data were analyzed from the World Health Organization’s Study on Global Ageing and Adult Health. Physical activity was assessed by the Global Physical Activity Questionnaire. Participants were dichotomized into low (i.e., not meeting 150 minutes of moderate physical activity per week) and moderate-to-high physically active groups. Associations between physical activity and a range of correlates were examined using multivariable logistic regressions. Results: The overall prevalence (95%CI) of people not meeting recommended physical activity levels in 34,129 participants (mean age 62.4 years, 52.1% female) was 23.5% (22.3%-24.8%). In the multivariable analysis, older age and unemployment were significant sociodemographic correlates of low physical activity. Individuals with low body mass index (<18.5kg/m2), bodily pain, asthma, chronic back pain, chronic obstructive pulmonary disease, hearing problems, stroke, visual impairment, slow gait, and weak grip strength were less likely to meet physical activity targets in the overall sample (P<0.05). The associations varied widely between countries. Conclusion: Our data illustrates that a multitude of factors influence physical activity target achievement in older adults, which can inform future interventions across low- and middle-income countries to assist people of this age group to engage in regular physical activity. Future prospective cohort studies are also required to investigate the directionality and mediators of the relationships observed

Psychological stress and short-term hospitalisations or death in patients with heart failure

Objective Standard predictors do not fully explain variations in the frequency and timing of heart failure (HF) adverse events (AEs). Psychological stress can trigger acute cardiovascular (CV) events, but it is not known whether stress can precipitate AEs in patients with HF. We investigated prospective associations of psychological stress with AEs in patients with HF. Methods 144 patients with HF (77% male; 57.5±11.5, range 23–87 years, left ventricular ejection fraction ≤40%) were longitudinally evaluated for psychological stress (Perceived Stress Scale) and AEs (CV hospitalisations/death) at 2-week intervals for 3 months and at 9-month follow-up. Results 42 patients (29.2%) had at least one CV hospitalisation and nine (6.3%) died. Patients reporting high average perceived stress across study measurements had a higher likelihood of AEs during the study period compared with those with lower stress (odds ratio=1.10, 95% confidence interval=1.04 to 1.17). In contrast to average levels, increases in stress did not predict AEs (p=0.96). Perceived stress was elevated after a CV hospitalisation (B=2.70, standard error (SE)=0.93, p=0.004) suggesting that CV hospitalisations increase stress. Subsequent analysis indicated that 24 of 38 (63%) patients showed a stress increase following hospitalisation. However, a prospective association between stress and AEs was present when accounting for prior hospitalisations (B=2.43, SE=1.23, p=0.05). Conclusions Sustained levels of perceived stress are associated with increased risk of AEs, and increased distress following hospitalisation occurs in many, but not all, patients with HF. Patients with chronically high stress may be an important target group for HF interventions aimed at reducing hospitalisations

A smoking cessation induction intervention via virtual reality headset during a dental cleaning: protocol for a randomized controlled trial

BACKGROUND: Effective smoking cessation programs exist but are underutilized by smokers, especially by disadvantaged smokers. Cessation interventions in dental settings have been shown to be effective, but are not consistently delivered due to provider burden and lack of training, especially on how to counsel smokers who are not motivated to quit. METHODS: This study is a 2-arm, phase III longitudinal randomized controlled efficacy trial to motivate utilization of evidenced based treatments (EBTs) for smoking cessation (e.g., state quitline, clinic-based counseling, the National Cancer Institute’s text message program, and pharmacotherapy). Patients attending an urban dental clinic (n = 376) will be randomized to an intervention group (INT; smoking cessation induction video delivered via VR headset during their teeth cleaning, brochure about EBTs, and a 4-week text message program) or control group (CTRL; relaxation video delivered via VR headset during teeth cleaning, the same brochure as INT, and assessment-only text messages). Assessments will occur at baseline, immediately after the clinic appointment, one-month post-appointment and 3-and 6 months later. We hypothesize INT will be more likely to contact EBTs vs CTRL and have greater utilization rates of EBTs. Secondary objectives are to test the efficacy of INT on point-prevalence smoking abstinence, quit smoking attempts, and motivation to quit vs. CTRL. DISCUSSION: Incorporating smoking cessation into a dental clinic visit and targeting all smokers, regardless of motivation to quit, provides proactive reach to cigarette smokers who otherwise may not seek treatment for smoking. TRIAL REGISTRATION: NCT04524533 Registered August 24, 2020