Mark Hamer

The effects of acute psychological stress on circulating inflammatory factors in humans: A review and meta-analysis

Stress influences circulating inflammatory markers, and these effects may mediate the influence of psychosocial factors on cardiovascular risk and other conditions such as psoriasis and rheumatoid arthritis. Inflammatory responses can be investigated under controlled experimental conditions in humans, and evidence is beginning to emerge showing that circulating inflammatory factors respond to acute psychological stress under laboratory conditions. However, research published to date has varied greatly in the composition of study groups, the timing of samples, assay methods, and the type of challenge imposed. The purpose of this review is to synthesize existing data using meta-analytic techniques. Thirty studies met inclusion criteria. Results showed robust effects for increased levels of circulating IL-6 (r=0.19, p=0.001) and IL-1beta (r=0.58, p<0.001) following acute stress, and marginal effects for CRP (r=0.12, p=0.088). The effects of stress on stimulated cytokine production were less consistent. Significant variation in the inflammatory response was also related to the health status of participants and the timing of post-stress samples. A number of psychobiological mechanisms may underlie responses, including stress-induced reductions in plasma volume, upregulation of synthesis, or enlargement of the cell pool contributing to synthesis. The acute stress-induced inflammatory response may have implications for future health, and has become an important topic of psychoneuroimmunological research.

Job strain as a risk factor for coronary heart disease: A collaborative meta-analysis of individual participant data

Summary Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985–2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10–1·37). This effect estimate was higher in published (1·43, 1·15–1·77) than unpublished (1·16, 1·02–1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15–1·48) and 5 years (1·30, 1·13–1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence.

BACKGROUND The association between physical activity and risk of neurodegenerative diseases is not well established. We therefore aimed to quantify this association using meta-analytical techniques. METHOD We searched Medline, the Cochrane Database of Systematic Reviews and Web of Science databases from 1990 to 2007 for prospective epidemiological studies of physical activity and incident dementia, Alzheimers and Parkinsons disease. We excluded studies of physical activity and cognitive decline without diagnosis of a neurodegenerative disease. Information on study design, participant characteristics, measurement of exposure and outcome variables, adjustment for potential confounding, and estimates of associations was abstracted independently by the two investigators. RESULTS We included 16 prospective studies in the overall analysis, which incorporated 163797 non-demented participants at baseline with 3,219 cases at follow-up. We calculated pooled relative risk (RR) using a random effects model. The RR of dementia in the highest physical activity category compared with the lowest was 0.72 [95% confidence interval (CI) 0.60-0.86, p<0.001], for Alzheimers, 0.55 (95% CI 0.36-0.84, p=0.006), and for Parkinsons 0.82 (95% CI 0.57-1.18, p=0.28). CONCLUSIONS Our results suggest that physical activity is inversely associated with risk of dementia. Future studies should examine the optimal dose of physical activity to induce protection, which presently remains unclear.

Do stress-related psychosocial factors contribute to cancer incidence and survival?

A substantial body of research has investigated the associations between stress-related psychosocial factors and cancer outcomes. Previous narrative reviews have been inconclusive. In this Review, we evaluated longitudinal associations between stress and cancer using meta-analytic methods. The results of 165 studies indicate that stress-related psychosocial factors are associated with higher cancer incidence in initially healthy populations (P = 0.005); in addition, poorer survival in patients with diagnosed cancer was noted in 330 studies (P <0.001), and higher cancer mortality was seen in 53 studies (P <0.001). Subgroup meta-analyses demonstrate that stressful life experiences are related to poorer cancer survival and higher mortality but not to an increased incidence. Stress-prone personality or unfavorable coping styles and negative emotional responses or poor quality of life were related to higher cancer incidence, poorer cancer survival and higher cancer mortality. Site-specific analyses indicate that psychosocial factors are associated with a higher incidence of lung cancer and poorer survival in patients with breast, lung, head and neck, hepatobiliary, and lymphoid or hematopoietic cancers. These analyses suggest that stress-related psychosocial factors have an adverse effect on cancer incidence and survival, although there is evidence of publication bias and results should be interpreted with caution.

The ABC of Physical Activity for Health: A consensus statement from the British Association of Sport and Exercise Sciences

Absract Our understanding of the relationship between physical activity and health is constantly evolving. Therefore, the British Association of Sport and Exercise Sciences convened a panel of experts to review the literature and produce guidelines that health professionals might use. In the ABC of Physical Activity for Health, A is for All healthy adults, B is for Beginners, and C is for Conditioned individuals. All healthy adults aged 18–65 years should aim to take part in at least 150 min of moderate-intensity aerobic activity each week, or at least 75 min of vigorous-intensity aerobic activity per week, or equivalent combinations of moderate- and vigorous-intensity activities. Moderate-intensity activities are those in which heart rate and breathing are raised, but it is possible to speak comfortably. Vigorous-intensity activities are those in which heart rate is higher, breathing is heavier, and conversation is harder. Aerobic activities should be undertaken in bouts of at least 10 min and, ideally, should be performed on five or more days a week. All healthy adults should also perform muscle-strengthening activities on two or more days a week. Weight training, circuit classes, yoga, and other muscle-strengthening activities offer additional health benefits and may help older adults to maintain physical independence. Beginners should work steadily towards meeting the physical activity levels recommended for all healthy adults. Even small increases in activity will bring some health benefits in the early stages and it is important to set achievable goals that provide success, build confidence, and increase motivation. For example, a beginner might be asked to walk an extra 10 min every other day for several weeks to slowly reach the recommended levels of activity for all healthy adults. It is also critical that beginners find activities they enjoy and gain support in becoming more active from family and friends. Conditioned individuals who have met the physical activity levels recommended for all healthy adults for at least 6 months may obtain additional health benefits by engaging in 300 min or more of moderate-intensity aerobic activity per week, or 150 min or more of vigorous-intensity aerobic activity each week, or equivalent combinations of moderate- and vigorous-intensity aerobic activities. Adults who find it difficult to maintain a normal weight and adults with increased risk of cardiovascular disease or type 2 diabetes may in particular benefit from going beyond the levels of activity recommended for all healthy adults and gradually progressing towards meeting the recommendations for conditioned individuals. Physical activity is beneficial to health with or without weight loss, but adults who find it difficult to maintain a normal weight should probably be encouraged to reduce energy intake and minimize time spent in sedentary behaviours to prevent further weight gain. Children and young people aged 5–16 years should accumulate at least 60 min of moderate-to-vigorous-intensity aerobic activity per day, including vigorous-intensity aerobic activities that improve bone density and muscle strength.

Chronic psychosocial factors and acute physiological responses to laboratory-induced stress in healthy populations: a quantitative review of 30 years of investigations.

This meta-analysis included 729 studies from 161 articles investigating how acute stress responsivity (including stress reactivity and recovery of hypothalamic-pituitary-adrenal [HPA] axis, autonomic, and cardiovascular systems) changes with various chronic psychosocial exposures (job stress; general life stress; depression or hopelessness; anxiety, neuroticism, or negative affect; hostility, aggression, or Type-A behavior; fatigue, burnout, or exhaustion; positive psychological states or traits) in healthy populations. In either the overall meta-analysis or the methodologically strong subanalysis, positive psychological states or traits were associated with reduced HPA reactivity. Hostility, aggression, or Type-A behavior was associated with increased cardiovascular (heart rate or blood pressure) reactivity, whereas anxiety, neuroticism, or negative affect was associated with decreased cardiovascular reactivity. General life stress and anxiety, neuroticism, or negative affect were associated with poorer cardiovascular recovery. However, regarding the sympathetic nervous system and parasympathetic nervous system, there were no associations between the chronic psychosocial factors and stress reactivity or recovery. The results largely reflect an integrated stress response pattern of hypo- or hyperactivity depending on the specific nature of the psychosocial background.

Metabolically Healthy Obesity and Risk of All-Cause and Cardiovascular Disease Mortality

CONTEXT Previous studies have identified an obese phenotype without the burden of adiposity-associated cardiometabolic risk factors, although the health effects remain unclear. OBJECTIVE We examined the association between metabolically healthy obesity and risk of cardiovascular disease (CVD) and all-cause mortality. DESIGN AND SETTING This was an observational study with prospective linkage to mortality records in community-dwelling adults from the general population in Scotland and England. PARTICIPANTS A total of 22,203 men and women [aged 54.1 (SD 12.7 yr), 45.2% men] without known history of CVD at baseline. INTERVENTIONS Based on blood pressure, high-density lipoprotein-cholesterol, diabetes diagnosis, waist circumference, and low-grade inflammation (C-reactive protein ≥ 3 mg/liter), participants were classified as metabolically healthy (0 or 1 metabolic abnormality) or unhealthy (two or more metabolic abnormalities). Obesity was defined as a body mass index of 30 kg/m(2) or greater. MAIN OUTCOME MEASURE Study members were followed up, on average, more than 7.0 ± 3.0 yr for cause-specific mortality. Cox proportional hazards models were used to examine the association of metabolic health/obesity categories with mortality. RESULTS There were 604 CVD and 1868 all-cause deaths, respectively. Compared with the metabolically healthy nonobese participants, their obese counterparts were not at elevated risk of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.74-2.13], although both nonobese (HR 1.59, 95% CI 1.30-1.94) and obese (HR 1.64, 95% CI 1.17-2.30) participants with two or more metabolic abnormalities were at elevated risk. Metabolically unhealthy obese participants were at elevated risk of all-cause mortality compared with their metabolically healthy obese counterparts (HR 1.72, 95% CI 1.23-2.41). CONCLUSION Metabolically healthy obese participants were not at increased risk of CVD and all-cause mortality over 7 yr.

Association between psychological distress and mortality: individual participant pooled analysis of 10 prospective cohort studies

Objective To quantify the link between lower, subclinically symptomatic, levels of psychological distress and cause-specific mortality in a large scale, population based study. Design Individual participant meta-analysis of 10 large prospective cohort studies from the Health Survey for England. Baseline psychological distress measured by the 12 item General Health Questionnaire score, and mortality from death certification. Participants 68 222 people from general population samples of adults aged 35 years and over, free of cardiovascular disease and cancer, and living in private households in England at study baseline. Main outcome measures Death from all causes (n=8365), cardiovascular disease including cerebrovascular disease (n=3382), all cancers (n=2552), and deaths from external causes (n=386). Mean follow-up was 8.2 years (standard deviation 3.5). Results We found a dose-response association between psychological distress across the full range of severity and an increased risk of mortality (age and sex adjusted hazard ratio for General Health Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to 1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26; P<0.001 for trend). This association remained after adjustment for somatic comorbidity plus behavioural and socioeconomic factors. A similar association was found for cardiovascular disease deaths and deaths from external causes. Cancer death was only associated with psychological distress at higher levels. Conclusions Psychological distress is associated with increased risk of mortality from several major causes in a dose-response pattern. Risk of mortality was raised even at lower levels of distress.

Walking and Primary Prevention: A Meta-analysis of Prospective Cohort Studies

Objective: To quantify the association between walking and the risk of cardiovascular disease (CVD) and all-cause mortality in healthy men and women. Data sources: Medline, Cochrane Database of Systematic Reviews, and Web of Science databases were searched to May 2007. Study selection: Prospective epidemiological studies of walking and CVD and all-cause mortality. Results: 18 prospective studies were included in the overall analysis, which incorporated 459 833 participants free from CVD at baseline with 19 249 cases at follow-up. From the meta-analysis the pooled hazard ratio of CVD in the highest walking category compared with the lowest was 0.69, (95% CI 0.61 to 0.77, p<0.001), and 0.68 (0.59 to 0.78, p<0.001) for all-cause mortality. These effects were robust among men and women, although there was evidence of publication biases for the associations with CVD risk. Walking pace was a stronger independent predictor of overall risk compared with walking volume (48% versus 26% risk reductions, respectively). There was also evidence of a dose–response relationship across the highest, intermediate, and lowest walking categories in relation to the outcome measures. Conclusions: The results suggest walking is inversely associated with clinical disease endpoints and largely support the current guidelines for physical activity. The mechanisms that mediate this relationship remain largely unknown and should be the focus of future research.

A bidirectional relationship between psychosocial factors and atopic disorders: A systematic review and meta-analysis.

Objective: There is growing epidemiological literature focusing on the bidirectional association between psychosocial factors and atopic disorders, but no efforts to quantify the relationship systematically have been published. Methods: We searched Medline, PsycINFO, Web of Science, and PubMed up to June 2007. The studies included were prospective cohort studies investigating the influence of psychosocial factors on atopic disorders and the effect of atopic disorders on mental health. Two investigators independently extracted data and determined study quality. Results: There were 43 studies (in 22 articles), of which 34 evaluated the effect of psychosocial factors on atopic disorders and 9 evaluated the effect of atopic disorders on mental health. The major atopic disease assessed in these studies was asthma (90.7%) with allergic rhinitis, 4.7%; atopic dermatitis, 2.3%; and food allergies, 2.3%. The overall meta-analysis exhibited a positive association between psychosocial factors and future atopic disorder (correlation coefficient (r) as combined size effect .024; 95% confidence interval, 0.014–0.035; p < .001) as well as between atopic disorders and future poor mental health (r = .044, 95% confidence interval, 0.021–0.067, p < .001). More notably, the subgroup meta-analysis on the healthy and atopic disorder populations showed psychosocial factors had both an etiological and prognostic effect on atopic disorders. Conclusions: The current review revealed a robust relationship between psychosocial factors and atopic disorders. This supports the use of psychological in addition to conventional physical and pharmacological interventions, in the successful prevention and management of atopic disorders. 95% CI = 95% confidence interval; r = correlation coefficient.