Daily stair climbing is associated with decreased risk for the metabolic syndrome.

BACKGROUND: Stair climbing can be a vigorous lifestyle physical activity, and is associated with healthier lipoprotein profiles, lower body weight and blood pressure, as well as higher aerobic fitness. The present analysis of data from a cohort of late middle-aged men and women examined the association between daily stair climbing and the metabolic syndrome. METHODS: Data from 782 (423 women) participants (mean (SD) age 58.3 (0.95) years in the Dutch Famine Birth Cohort Study (2002-2004) were used to examine the cross-sectional association between self-reported daily stair climbing and the metabolic syndrome. Stair climbing was assessed by the question 'Do you climb stairs daily?' and the metabolic syndrome was defined using the established five components relating to lipid fractions, blood glucose levels, blood pressure and abdominal obesity. RESULTS: Not climbing stairs daily was associated with an increased incidence of the metabolic syndrome (OR = 1.90, 95% CI = 1.23, 2.92, p = 0.004) and a greater number of its components (F1,780 = 8.48, p = 0.004): these associations were still evident after adjusting for a variety of potential confounders. CONCLUSIONS: The most likely explanation for the current findings is that daily stair climbing may be protective against the metabolic syndrome. This result reinforces public health recommendations for increased stair climbing with evidence from physiological outcomes.

Signage Interventions for Stair Climbing at Work: More than 700,000 Reasons for Caution.

Increased stair climbing reduces cardiovascular disease risk. While signage interventions for workplace stair climbing offer a low-cost tool to improve population health, inconsistent effects of intervention occur. Pedestrian movement within the built environment has major effects on stair use, independent of any health initiative. This paper used pooled data from UK and Spanish workplaces to test the effects of signage interventions when pedestrian movement was controlled for in analyses. Automated counters measured stair and elevator usage at the ground floor throughout the working day. Signage interventions employed previously successful campaigns. In the UK, minute-by-minute stair/elevator choices measured effects of momentary pedestrian traffic at the choice-point (n = 426,605). In Spain, aggregated pedestrian traffic every 30 min measured effects for 'busyness' of the building (n = 293,300). Intervention effects on stair descent (3 of 4 analyses) were more frequent than effects on stair climbing, the behavior with proven health benefits (1 of 4 analyses). Any intervention effects were of small magnitude relative to the influence of pedestrian movement. Failure to control for pedestrian movement compromises any estimate for signage effectiveness. These pooled data provide limited evidence that signage interventions for stair climbing at work will enhance population health.

Assessment of the cerebral pressure-flow relationship using psychological stress to manipulate blood pressure.

Recent evidence indicates that cerebral autoregulation (CA) might be more pressure passive than previously thought. That is, cerebral blood flow, traditionally thought to be regulated independently of prevailing mean arterial pressure (MAP), might fluctuate, to some extent, as a function of MAP. However, due to limitations associated with experimental usage of pharmaceuticals to manipulate MAP and inconsistent control of arterial carbon dioxide, questions remain regarding the MAP-cerebral blood flow relationship, especially during typical daily activities that alter MAP. Therefore, the current study aimed to assess CA using a nonpharmacological acute psychological stress task to augment MAP, while at the same time controlling for end-tidal carbon dioxide (PET CO2 ). Twenty-five healthy young adults completed a stressful task while continuous measures of MAP, middle cerebral artery blood flow velocity (MCAv), and PET CO2 were recorded. Slope values obtained from hierarchical linear regression were used to assess the strength of the MAP-MCAv relationship and control for PET CO2 . The stress task significantly increased MAP (p < 0.001) and MCAv (p < 0.001), and decreased PET CO2 (p = 0.05). For every 10 mmHg task-induced increase in MAP, MCAv increased by ≈3.5%; task-induced changes in PET CO2 did not appreciably change the MAP-MCAv relationship. Greater task-induced MAP responses were significantly related to decreased MAP-MCAv slope values, consistent with CA. These data support the hypothesis that CA is more pressure passive than previously thought and provide initial evidence indicating that a pressure-passive MAP-MCAv relationship may play a role in the observed associations between MAP stress responses, stroke, and cerebrovascular disease.

The utility of saliva for the assessment of anti-pneumococcal antibodies: investigation of saliva as a marker of antibody status in serum.

CONTEXT: Salivary antibodies may act as non-invasive marker of systemic immunity enabling assessment of vaccination and protection against bacterial infections. OBJECTIVE: To assess if levels of anti-pneumococcal (Pn) antibodies in saliva reflect concentrations in serum and determine whether saliva can accurately identify protective concentrations in serum. METHODS: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 Pn polysaccharide antigens in 72 healthy adults. RESULTS: Antibody levels in saliva correlated positively with serum across immunoglobulin classes, most strongly for IgA. Individuals who had protective antibody levels in serum demonstrated significantly higher IgG and IgA salivary antibody concentrations/secretion rates. Salivary IgG and IgA Pn antibodies were able to distinguish between those with/without protective levels in serum for the majority of serotypes. Salivary IgM antibodies were not able to differentiate protective status. Median IgG and IgA Pn salivary parameters were able to identify individuals who had protective levels in serum on ≥8/12 serotypes with moderate accuracy: median IgA secretion rates provided the best sensitivity (73%) and specificity (71%). CONCLUSIONS: These findings suggest that IgG and IgA Pn specific antibodies in saliva may be useful surrogate markers of antibody status in serum.

The behavioural, cognitive, and neural corollaries of blunted cardiovascular and cortisol reactions to acute psychological stress.

Recent research shows that blunted cardiovascular and cortisol reactions to acute psychological stress are associated with adverse behavioural and health outcomes: depression, obesity, bulimia, and addictions. These outcomes may reflect suboptimal functioning of the brain's fronto-limbic systems that are needed to regulate motivated behaviour in the face of challenge. In support of this, brain imaging data demonstrate fronto-limbic hypoactivation during acute stress exposure. Those demonstrating blunted reactions also show impairments of motivation, including lower cognitive ability, more rapid cognitive decline, and poorer performance on motivation-dependent tests of lung function. Persons exhibiting blunted stress reactivity display well established temperament characteristics, including neuroticism and impulsivity, characteristic of various behavioural disorders. Notably, the outcomes related to blunted stress reactivity are similar to those that define Reward Deficiency Syndrome. Accordingly, some individuals may be characterised by a broad failure in cardiovascular and cortisol responding to both stress and reward, reflecting fronto-limbic dysregulation. Finally, we proffer a model of blunted stress reactivity, its antecedents and sequelae, and identify future research priorities.

Exploring the possible mechanisms of blunted cardiac reactivity to acute psychological stress.

Blunted cardiovascular reactivity to acute psychological stress has been linked to a range of adverse health and behavioral outcomes. However, the origins of blunted reactivity remain unclear. The current study aimed to explore the following possibilities: different appraisals of task stressfulness and/or difficulty, diminished task effort, or reduced physiological capacity to respond. Individuals characterized, via pre-screening, as blunted (n=17) or exaggerated (n=16) heart rate (HR) reactors to acute psychological stress (socially evaluative mental arithmetic) were exposed to a psychological stress, cold pressor and exercise tasks during a follow-up testing session while HR and blood pressure (BP) were measured. At follow-up, groups again mounted significantly different HR reactions to psychological stress, despite reporting similar levels of subjective stress and difficulty, and achieving similar tasks scores (measure of task effort) at both testing sessions. In response to the cold pressor and exercise blunted and exaggerated reactors displayed similar HR and BP responses. Results indicated that blunted reactors do not differ from exaggerated reactors on appraisals of task stressfulness or difficulty, or objective task effort, and do possess the physiological capacity to respond to other laboratory challenges. Other sources of blunted stress reactivity remain to be explored.

Blunted cardiac stress reactors exhibit relatively high levels of behavioural impulsivity.

Blunted physiological reactions to acute psychological stress are associated with a range of adverse health and behavioural outcomes. This study examined whether extreme stress reactors differ in their behavioural impulsivity. Individuals showing blunted (N=23) and exaggerated (N=23) cardiovascular reactions to stress were selected by screening a healthy student population (N=276). Behavioural impulsivity was measured via inhibitory control and motor impulsivity tasks. Blunted reactors exhibited greater impulsivity than exaggerated reactors on both stop-signal, F(1,41)=4.99, p=0.03, ηp(2)=0.108, and circle drawing, F(1,43)=4.00, p=0.05, η p(2)=0.085, tasks. Individuals showing blunted cardiovascular stress reactions are characterized by greater impulsivity which may contribute to their increased susceptibility to outcomes such as obesity and addiction.

Diminished heart rate reactivity to acute psychological stress is associated with enhanced carotid intima-media thickness through adverse health behaviors.

Recent evidence demonstrates that individuals with low heart rate (HR) reactions to acute psychological stress are more likely to be obese or smokers. Smoking and obesity are established risk factors for increased carotid intima-media thickness (IMT). The aim of this study was to examine the potential pathways linking intima-media thickness, smoking, body mass index (BMI), and HR stress reactivity. A total of 552 participants, 47.6% male, M (SD) age = 58.3 (0.94) years, were exposed to three psychological stress tasks (Stroop, mirror drawing, and speech) preceded by a resting baseline period; HR was recorded throughout. HR reactivity was calculated as the average response across the three tasks minus average baseline HR. Smoking status, BMI, and IMT were determined by trained personnel. Controlling for important covariates (e.g., socioeconomic status), structural equation modeling revealed that BMI and smoking mediated the negative relationship between HR reactivity and IMT. The hypothesized model demonstrated a good overall fit to the data, χ(2) (8) = 0.692, p = .403; CFI = 1.00; TLI = 1.00 SRMR = .01; RMSEA < .001 (90% CI < 0.01-0.11). HR reactivity was negatively related to BMI (ß = -.16) and smoking (ß = -.18), and these in turn were positively associated with IMT (BMI: ß = .10; smoking: ß = .17). Diminished HR stress reactivity appears to be a marker for enlarged IMT and appears to be exerting its impact through already established risks. Future research should examine this relationship longitudinally and aim to intervene early.

Anxiety symptom interpretation: A potential mechanism explaining the cardiorespiratory fitness-anxiety relationship.

BACKGROUND: Higher cardiorespiratory fitness is associated with lower trait anxiety, but research has not examined whether fitness is associated with state anxiety levels and the interpretation of these symptoms. The aim of this paper was to (1) reexamine the association between cardiorespiratory fitness and general anxiety and (2) examine anxiety intensity and perceptions of these symptoms prior to an acute psychological stress task. METHODS: Participants (N=185; 81% female; Mage=18.04, SD=0.43 years) completed a 10-minute Paced Serial Addition Test. General anxiety was assessed using the anxiety subscale of the Hospital Anxiety Depression Scale. Cognitive and somatic anxiety intensity and perceptions of symptoms was assessed immediately prior to the acute psychological stress task using the Immediate Anxiety Measures Scale. Cardiorespiratory fitness was calculated using a validated standardized formula. RESULTS: Higher levels of cardiorespiratory fitness were associated with lower levels of general anxiety. Path analysis supported a model whereby perceptions of anxiety symptoms mediated the relationship between cardiorespiratory fitness and levels of anxiety experienced during the stress task; results remained significant after adjusting for general anxiety levels. Specifically, higher levels of cardiorespiratory fitness were positively associated with more positive perceptions of anxiety symptoms and lower levels of state anxiety. LIMITATIONS: A standard formula rather than maximal testing was used to assess cardiorespiratory fitness, self-report questionnaires were used to assess anxiety, and the study was cross-sectional in design. CONCLUSIONS: Results suggest a potential mechanism explaining how cardiorespiratory fitness can reduce anxiety levels.

Neutrophil function in young and old caregivers.

OBJECTIVE: The present study examined the effects of caregiving stress and ageing on neutrophil function in young and older individuals. DESIGN: As a model of caregiving, young parents (aged 38.3 ± 4.78) of children with developmental disabilities were recruited and compared to older caregivers (aged 70 ± 6.03), full time carers of a spouse with dementia. Age- and gender-matched controls were also assessed. METHODS: Participants completed a questionnaire pack assessing health behaviours, psychosocial status and caregiving characteristics, and provided a blood sample for assay of neutrophil function (phagocytosis of Escherichia coli and generation of reactive oxygen species to E. coli). RESULTS: Despite scoring poorly on the majority of psychological and caregiving variables, neutrophil function in caregivers was comparable to that in controls and was unexpectedly higher in older adults when compared to younger adults overall. However, those caregivers who reported higher psychological morbidity (depression, perceived stress, poor sleep quality), and more burdensome caregiving showed some evidence of poorer neutrophil phagocytic function. CONCLUSION: To our knowledge, this is the first study to examine the effect of caregiving stress on neutrophil function in young and older participants simultaneously. Overall, neutrophil function was preserved in caregivers with neutrophil phagocytosis compromised only in those with the highest levels of distress. This suggests that, in future studies, more attention should be paid to individual differences among caregivers rather than caregiving status per se. STATEMENT OF CONTRIBUTION: What is already known on this subject? Ageing is accompanied by the decrease in innate and adaptive immunity, termed immunosenescence. Caregiving stress has been shown to exert negative effect on immune function in both young and old. What does this study add? The study examined effect of caregiving and ageing simultaneously in four groups of participants. Neutrophil function and stress hormone levels were preserved in the stressed in both age groups. Those with higher psychological morbidity had poorer neutrophil phagocytosis.

Heart rate complexity: A novel approach to assessing cardiac stress reactivity.

Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function.

Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study.

Immunoglobulins are essential for combating infectious disease although very high levels can indicate underlying pathology. The present study examined associations between secretory immunoglobulin A (sIgA) in saliva and mortality rates in the general population. Participants were 639 adults from the eldest cohort of the West of Scotland Twenty-07 Study aged 63 years at the time of saliva sampling in 1995. From unstimulated 2-minute saliva samples, saliva volume and S-IgA concentration were measured, and S-IgA secretion rate determined as their product. Mortality data were tracked for 19 years. Cox proportional hazard models were applied to compute hazard ratios (HR) for all-cause mortality from sIgA secretion rate. Associations were adjusted for gender, assay batch, household occupational group, smoking, medication usage, and self-reported health. There was a negative association between log sIgA secretion rate and all-cause mortality, HR = 0.81, 95%CI = 0.73-0.91, p < .001. Further analysis of specific causes of mortality revealed that the all-cause association was due to an underlying association with cancer mortality and in particular with cancers other than lung cancer. The HR for non-lung cancer was 0.68 (95%CI = 0.54 to 0.85) implying a 32% reduction in mortality risk per standard deviation rise in log sIgA secretion rate. Effects were stronger for men than women. For deaths from respiratory diseases, sIgA secretion had a non-linear relationship with mortality risk whereby only the very lowest levels of secretion were associated with elevated risk. SIgA concentration revealed a similar but weaker pattern of association. In the present study, higher secretion rates of sIgA were associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease. Thus, it appears that sIgA plays a protective role among older adults, and could serve as a marker of mortality risk, specifically cancer mortality.

Salivary Functional Antibody Secretion Is Reduced in Older Adults: A Potential Mechanism of Increased Susceptibility to Bacterial Infection in the Elderly.

BACKGROUND: Bacterial infections in the elderly are common and associated with high morbidity and mortality, with pneumonia the second commonest cause of death. Reductions in antibodies against specific bacterial antigens in saliva and serum could contribute to infection risk in older adults, although they have yet to be examined in relation to age. METHOD: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 pneumococcal, 4 meningococcal and haemophilus polysaccharide antigens and diphtheria and tetanus toxoids in healthy younger (n = 28, 21-34 years) and older (n = 44, 60-80 years) adults. RESULTS: Older adults had lower antibody concentrations in saliva than young adults, with the most striking differences observed for salivary antibody secretion rates. In serum, older adults registered lower concentrations for only a minority of antibodies. Young adults who had previously received a polysaccharide pneumococcal vaccination (PPV23) had higher levels of anti-pneumococcal antibodies in serum and in saliva. Only minor differences were observed in antibody levels between older adults who had/had not received PPV23, and there was no evidence of memory in saliva. CONCLUSIONS: Age differences were much greater in salivary antibodies than in serum; older adults had reduced salivary secretion rates of antibodies across bacterial antigens. This decline in local immunity may contribute to increased infection risk in the elderly. The poor memory from pneumococcal vaccination in serum and saliva suggests that PPV23 may be ineffective in older adults for both systemic and local protection.

Cardiac stress reactions and perseverance: Diminished reactivity is associated with study non-completion.

Blunted cardiovascular stress reactions may be a marker for poor behavioral regulation. The present study examined the association between heart rate reactivity and perseverance, operationalized as the failure to complete a subsequent follow-up assessment. The heart rate (using electrocardiography), cardiac output (using Doppler echocardiography) and blood pressure (using a semi- automatic sphygmomanometer) of 176 high school students were measured before and during exposure to a standard 10-min mental arithmetic stress. A year later, all participants were contacted to complete a simple and undemanding on-line assessment. Despite repeated promptings, 44 failed to do so. Diminished heart rate and cardiac output stress reactions predicted failure to complete the follow-up. This result adds to the emerging characterization of those who exhibit blunted stress reactions by revealing associated deficiencies in perseverance. It may also have prognostic implications for the completion of multi-session interventions, as well as for selection bias in stress reactivity studies with follow-up designs.

Cardiovascular and cortisol reactions to acute psychological stress under conditions of high versus low social evaluative threat: associations with the type D personality construct.

OBJECTIVES: Social evaluative threat is an important factor in the cardiovascular response to mental stress. This study examined whether Type D personality, characterized by social inhibition and negative affectivity, is associated with an adverse cardiovascular response to a non-social and social evaluative threat. METHODS: A total of 2300 students were screened for Type D personality, and 130 were selected for a nonsocial stress exposure condition (31 Type D, 30 non-Type D: 52% female) or a condition high in social evaluative threat (35 Type D, 34 non-Type D: 55% female). Systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and salivary cortisol were measured. RESULTS: Social evaluative threat resulted in higher cardiovascular responses than the nonsocial challenge (SBP, p = .001, η = 0.092;DBP, p = .006, η = 0.058;HR, p = .006, η = 0.059). The greatest cardiovascular stress reactions were exhibited by Type D participants in the high social evaluation condition; reflected in significant group by condition interactions for SBP (F(1,126) = 7.29, p = .008, η = 0.055), DBP (F(1,126) = 5.23, p = .024, η = 0.040), and HR (F(1,126) = 5.04, p = .027, η = 0.038) reactivity. Only Type Ds in the social condition mounted a positive cortisol response (F(1,33) = 5.07, p = .031, η = 0.133). CONCLUSIONS: Type D individuals show different stress reactions depending on the social evaluative nature of the stress exposure. These findings suggest that dysregulation of the stress response in social situations potentially increases cardiovascular disease risk.

Problematic Internet use, excessive alcohol consumption, their comorbidity and cardiovascular and cortisol reactions to acute psychological stress in a student population.

BACKGROUND AND AIMS: Problematic Internet use and excessive alcohol consumption have been associated with a host of maladaptive outcomes. Further, low (blunted) cardiovascular and stress hormone (e.g. cortisol) reactions to acute psychological stress are a feature of individuals with a range of adverse health and behavioural characteristics, including dependencies such as tobacco and alcohol addiction. The present study extended this research by examining whether behavioural dependencies, namely problematic Internet use, excessive alcohol consumption, and their comorbidity would also be associated with blunted stress reactivity. METHODS: A large sample of university students (N = 2313) were screened using Internet and alcohol dependency questionnaires to select four groups for laboratory testing: comorbid Internet and alcohol dependence (N = 17), Internet dependence (N = 17), alcohol dependence (N = 28), and non-dependent controls (N = 26). Cardiovascular activity and salivary cortisol were measured at rest and in response to a psychological stress protocol comprising of mental arithmetic and public speaking tasks. RESULTS: Neither problematic Internet behaviour nor excessive alcohol consumption, either individually or in combination, were associated with blunted cardiovascular or cortisol stress reactions. Discussion It is possible that problematic Internet behaviour and excessive alcohol consumption in a student population were not related to physiological reactivity as they may not reflect ingrained addictions but rather an impulse control disorder and binging tendency. CONCLUSIONS: The present results serve to indicate some of the limits of the developing hypothesis that blunted stress reactivity is a peripheral marker of the central motivational dysregulation in the brain underpinning a wide range of health and behavioural problems.

Negative life events and symptoms of depression and anxiety: stress causation and/or stress generation.

BACKGROUND AND OBJECTIVES: Stressful life events are known to contribute to development of depression; however, it is possible this link is bidirectional. The present study examined whether such stress generation effects are greater than the effects of stressful life events on depression, and whether stress generation is also evident with anxiety. DESIGN: Participants were two large age cohorts (N = 732 aged 44 years; N = 705 aged 63 years) from the West of Scotland Twenty-07 study. METHODS: Stressful life events, depression, and anxiety symptoms were measured twice five years apart. Cross-lagged panel analysis examined the mutual influences of stressful life events on depression and on anxiety over time. RESULTS: Life events predicted later depressive symptomatology (p = .01), but the depression predicting life events relationship was less strong (p = .06), whereas earlier anxiety predicted life events five years later (p = .001). There was evidence of sex differences in the extent to which life events predicted later anxiety. CONCLUSIONS: This study provides evidence of stress causation for depression and weaker evidence for stress generation. In contrast, there was strong evidence of stress generation for anxiety but weaker evidence for stress causation, and that differed for men and women.

Evaluation of a Pharmacist-Specific Intervention on 30-Day Readmission Rates for High-Risk Patients with Pneumonia.

BACKGROUND: Pharmacist interventions have been shown to have an impact on reducing readmission rates, however further research is necessary to target resources to high-risk populations and determine the most effective bundle of interventions. OBJECTIVE: To evaluate the effect of a pharmacist-bundled intervention on 30-day readmission rates for high-risk patients with pneumonia. METHODS: A pilot study with a historical control conducted at a community, teaching-affiliated medical center. Up to 65 selected subjects were included if they had pneumonia and any of the following high-risk criteria: admission within 6 months, at least 5 scheduled home medications, chronic obstructive pulmonary disease (COPD), or heart failure. A retrospective chart review was conducted to compile the historical control group that received usual care between June and November 2013. Patients admitted from December 2013 through March 2014 were reviewed to receive a bundled intervention. The primary outcome was 30-day readmission rates. Risk factors and reasons for readmission, pharmacist clinical interventions, and the time interval between discharge and readmission were also evaluated. RESULTS: A trend toward a reduced 30-day readmission rate was observed in the intervention group (n = 43) compared to those who received usual care (n = 65) (27.9% vs 40.0%; relative risk [RR], 0.6977; 95% CI, 0.3965-1.2278; P = .2119). The most commonly identified high-risk inclusion criteria were having at least 5 scheduled home medications and COPD. The time interval between discharge and readmission did not considerably differ between groups (10.8 vs 10.6 days). CONCLUSIONS: The pharmacist-bundled intervention was associated with a reduced 30-day readmission rate for high-risk patients with pneumonia.

The association between spirituality and depression in parents caring for children with developmental disabilities: social support and/or last resort.

Associations between spirituality and depression were examined in parents of children with developmental disabilities using both quantitative and qualitative methodology. Spirituality was positively associated with depression, whereas social support was negatively related; parents with higher spiritual beliefs and lower levels of support had higher depression scores. Themes emerging from interviews were spiritual/religious coping as a way of dealing with difficulty, as a last resort, and as a form of release from their situation. Associations between spirituality and depression in these parents are more complex than previously thought.

Raised levels of immunoglobulin G, A and M are associated with an increased risk of total and cause-specific mortality: the Vietnam Experience Study.

BACKGROUND: Immunoglobulins (Ig) are essential for combating infectious disease. However, high levels are associated with a range of diseases and/or poor health behaviours, such as autoimmune diseases, chronic infection, HIV and excessive alcohol consumption. In the present analyses, we extend this body of work by examining whether higher levels of serum Ig G, A and M are associated with increased mortality risk. METHODS: Participants were 4255 Vietnam-era, former US army personnel (the Vietnam Experience Study). From military service files, telephone interviews in 1983 and a medical examination in 1986, sociodemographic, and health data were collected. Contemporary morning fasted blood samples were taken from which IgG, IgA and IgM concentrations were determined. Mortality surveillance over 15 years gave rise to deaths ascribed to all-causes, cardiovascular disease mortality, all cancers combined mortality, external cause and 'other' causes (predominantly comprising deaths due to infectious disease). Cox proportional hazard models were utilised to compute HRs per SD increase in Ig which were first adjusted for age and then additionally adjusting for a range of candidate confounders. RESULTS: In multiply adjusted analyses, in general, the higher the immunoglobulin concentration, the greater the risk of death. Thus, IgA (HR=2.0 95% CI 1.47 to 2.73), IgM (HR=1.5 95% CI 1.11 to 1.91) and IgG (HR=5.8 95% CI 3.38 to 9.95) were positively related to all-cause mortality. Corresponding results for 'other' causes of mortality were 4.7 (2.64 to 8.19), 3.5 (2.29 to 5.45) and 33.4 (15.13 to 73.64). CONCLUSIONS: In the present study, high levels of Ig are associated with an elevated risk of death from total and 'other' causes, mainly infectious disease. High levels of Ig, particularly IgG, may signal subclinical disease.