Joachim E. Fischer

Allostatic load and work conditions

Adverse work characteristics and poor social support have been associated with an increased risk for cardiovascular disease and other adverse health outcomes in otherwise apparently healthy adults. We undertook a cross-sectional study to evaluate the relationship between objective health status and work characteristics in industrial workers in Germany. Volunteers (n=324) were recruited from a representative random sample (n=537) of employees of an airplane manufacturing plant. Psychosocial work characteristics were assessed by the 52-item, 13-subscale salutogenetic subjective work analysis (SALSA) questionnaire, which assesses potentially salutogenic and pathogenic conditions. Factor analysis revealed three factors: decision latitude, job demands and social support. Biological health status was determined by the revised allostatic load score with 14 components: body-mass index, waist-to-hip ratio; systolic and diastolic blood pressure; plasma levels of C-reactive protein (CRP), tumor-necrosis factor-alpha, HDL, cholesterol, dehydroepiandrosterone sulfate; glycosylated hemoglobin; urinary cortisol, epinephrine, norepinephrine, and albumin. Score points were given for values in the high-risk quartile (maximum=14). General linear models revealed that older individuals and men had significantly higher allostatic load scores than younger participants or women. Of the SALSA factors, only job demands related significantly to allostatic load. The effect of demands was stronger in older individuals. Post-hoc analysis showed possible positive associations between high job demands and blood pressure or CRP, and between low social support and nocturnal excretion of cortisol or plasma levels of CRP. We conclude that this cross-sectional study on industrial employees found a weak association between a health summary score based on objective medical data and self-reported adverse work characteristics.

The Interrelationship of Psychosocial Risk Factors for Coronary Artery Disease in a Working Population: Do We Measure Distinct or Overlapping Psychological Concepts?

There is growing evidence that psychosocial factors contribute to the risk of coronary artery disease. Commonly used psychometric scales share several features leading to questions about whether they reflect distinguishable concepts. Study participants were 822 employees of the Augsburg Cohort Study (mean age 40 years, 89% men). The authors analyzed the interrelationship between the following psychosocial measures by applying Pearson correlations and factor analysis to the Hospital Anxiety and Depression Scale (HADS), Type D Personality (DS14), the Maastricht Vital Exhaustion Questionnaire (VE), Social Support (F-SozU), the SF12 Health Survey, and Effort-Reward Imbalance. Although the full correlation matrix revealed low to medium associations supporting the notion that the applied psychometric scales show some conceptual overlap, factor analyses resulted in 13 distinguishable and interpretable factors, considerably reflecting the original psychometric scales. This strengthens the assumption that the psychometric scales used constitute distinct psychological concepts, in particular, depressive symptomatology and negative affectivity versus vital exhaustion.

Health-Related Quality of Life Measured by the SF12 in Working Populations: Associations With Psychosocial Work Characteristics

This study investigated the contribution of psychosocial work characteristics (decision latitude, job demand, social support at work, and effort-reward imbalance) to health-related quality of life. Data were derived from 2 aircraft manufacturing plants (N=1,855) at the start of a longitudinal study. Regression analysis showed that work characteristics (1st model) explained 19% of the variance in the mental summary score of the Short Form-12 Health Survey. R2 change for work characteristics decreased to 13%, accounting for demographics, socioeconomic status, body mass index, and medical condition (5th model). Including health behavior and personality factors (full model), R2 change for work characteristics remained significant. Psychosocial work characteristics account for relevant proportions in the subjective perception of mental health beyond a wide array of medical variables and personality factors.

Elevated plasma C-reactive protein in chronically distressed subjects who carry the A allele of the TNF-α -308 G/A polymorphism

Objective: Sustained psychological stress may result in a state operationalized as “vital exhaustion.” Exhaustion predicted coronary artery disease (CAD) events whereby increased inflammatory activity might mediate this link. Moreover, there is an emerging importance of gene–environmental interactions in CAD. We investigated the effect of exhaustion severity on plasma levels of C-reactive protein (CRP) and whether exhaustion might regulate CRP levels via the −308G/A polymorphism of the tumor necrosis factor (TNF)-α gene. Methods: We assessed exhaustion in 275 industrial employees (mean age ± SD, 41 ± 9 years, 88% men) using the Maastricht Questionnaire. Subjects were stratified as per exhaustion severity: none (N = 80), moderate (N = 128), and severe (N = 67). The TNF-α polymorphism was determined by real-time polymerase chain reaction, and plasma CRP levels were measured by a high-sensitivity immunoassay. Results: There was a significant interaction between exhaustion and the TNF-α polymorphism, explaining 4.5% in the variance of plasma CRP values (F (5,271) = 2.47, p = .033); the result held after controlling for classic cardiovascular risk factors. Adjusted mean CRP levels across exhaustion strata in GA (N = 70) and AA (N = 3) carriers combined were 0.91 mg/l (none), 1.78 mg/l (moderate), and 2.61 mg/l (severe) as compared with 1.24 mg/l, 1.61 mg/l, and 1.36 mg/l for the GG wild-type (N = 202). Conclusion: The findings suggest that the A allele of the TNF-α −308 G/A polymorphism may mediate inflammation with exhaustion in a dose-response relationship, while with the GG wild-type exhaustion severity seems unrelated to CRP levels. The finding provides a rationale for gene-environmental interactions by which psychosocial factors may promote atherosclerosis and CAD.

Different contribution of interleukin-6 and cortisol activity to total plasma fibrin concentration and to acute mental stress-induced fibrin formation

Acute mental stress may contribute to atherosclerosis by affecting inflammation and coagulation; however, the crosstalk between inflammation and coagulation during stress has not been studied. In the present study, we investigated the association of plasma fibrinogen, plasma IL-6 (interleukin-6) and free salivary cortisol with the procoagulant marker D-dimer reflecting fibrin formation both over a 2-h period and in response to acute mental stress. Twenty-one male volunteers (mean age, 47+/-8 years) underwent the Trier Social Stress Test combining a 3-min preparation phase, a 5-min job interview and 5-min mental arithmetic test before an audience. IL-6, fibrinogen, D-dimer and cortisol were measured immediately before and after stress, and after 45 min and 105 min of recovery from stress. Two distinct areas under the curve were computed to obtain integrated measures of total protein activity over the entire 2-h period and of stress reactivity of proteins. IL-6 (P < 0.001), fibrinogen (P = 0.001), D-dimer (P = 0.021) and cortisol (P < 0.001) had all significantly changed across the four time points assessed, as determined by ANOVA. For the entire 2-h period, total fibrinogen activity (R2 = 0.33, P = 0.007) and total cortisol activity (DeltaR2 = 0.17, P = 0.034) explained 50% of the variance in total D-dimer activity. Stress-induced changes in fibrinogen (R2 = 0.47, P = 0.001) and IL-6 (DeltaR2 = 0.18, P = 0.008) together explained 65% of the variance in D-dimer reactivity to stress. Total fibrin formation was independently predicted by fibrinogen and hypothalamo-pituitary-adrenal activity. Pro-inflammatory and procoagulant changes with stress were associated. Aside from fibrinogen reactivity, IL-6 reactivity was an independent predictor of stress-induced fibrin formation.

Independent relation of vital exhaustion and inflammation to fibrinolysis in apparently healthy subjects

Objective—Vital exhaustion (VE) and a hypercoagulable state both have been associated with coronary artery disease (CAD). Candidate mechanisms by which VE predicts CAD events are impaired fibrinolysis and inflammatory changes, the latter also affecting hemostasis. We investigated whether VE and inflammation would independently relate to hemostasis. Design—Study participants were 217 (mean ageu2005±u2005SD, 40u2005±u20059 years) apparently healthy men and women working at an airplane manufacturing plant in Germany who completed the Shortened 9‐item VE Maastricht Questionnaire. All subjects had a set of classic cardiovascular risk factors assessed, and plasma levels of fibrin D‐dimer, type I plasminogen activator inhibitor (PAI‐1) antigen, C‐reactive protein (CRP), and tumor necrosis factor (TNF)‐α were measured. Results—PAI‐1 correlated with VE (ru2005=u20050.18, pu2005=u20050.009), CRP (ru2005=u20050.20, pu2005=u20050.004), and TNF‐α (ru2005=u20050.18, pu2005=u20050.009); D‐dimer correlated with CRP (ru2005=u20050.16, pu2005=u20050.018). In linear regression analyses, VE and TNF‐α independently explained 2 and 1%, respectively, of the variance in PAI‐1. Conclusion—Our study corroborates previous findings on impaired fibrinolysis in VE. The findings suggest that VE and inflammation may impair fibrinolysis by different pathways, and independently of traditional cardiovascular risk factors.

Hypercoagulability in working men and women with high levels of panic-like anxiety

Background: There is growing evidence that cardiovascular diseases are relatively more prevalent in subjects who feel anxious. An increased clotting diathesis might subject anxious individuals to an elevated arterial thrombotic risk. We investigated whether panic-like anxiety would relate to a hypercoagulable state. Methods: Study participants with a complete data set were 691 employees (mean age ± SD 40 ± 11 years, 83% men) recruited from two German companies. Subjects were asked to self-rate the onset of sudden feelings of panic in the previous week on a 4-point Likert scale: 0 = not at all (n = 416), 1 = not very often (n = 179), 2 = quite often (n = 55), and 3 = very often indeed (n = 41). Levels of fibrinogen, of the antifibrinolytic enzyme type 1 plasminogen activator inhibitor (PAI-1), and of the hypercoagulability marker fibrin D-dimer were measured in plasma. Results: While the level of D-dimer was significantly different across the 4 scores of panic feelings (F3, 687 = 6.49, p < 0.001), the levels of fibrinogen and PAI-1 were not. After having controlled for a range of confounders of hemostatic function, the 96 subjects reporting panic feelings either ‘quite often’ or ‘very often indeed’ had higher D-dimer levels (mean ± SEM 165 ± 12.0 vs. 145 ± 4.3 ng/ml, F20, 670 = 4.78, p = 0.030) and lower fibrinogen levels (259 ± 6.9 vs. 274 ± 2.5 mg/dl, F20, 670 = 4.71, p = 0.030) than the 595 subjects reporting panic feelings either ‘not at all’ or ‘not very often’. Conclusions: The findings suggest increased fibrin turnover with sudden feelings of panic. Prospective studies need to show whether such a procoagulant mechanism may contribute to the increased coronary risk with panic-like anxiety.

Objectifying psychomental stress in the workplace - an example

Abstractu2002Background:u2002Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. Design:u2002Repeated measurements observational cohort study (before and after intervention). Subjects:u200284 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. Measurements and interventions:u2002Salivary cortisol samples were collected every 2u2009h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. Main results:u2002Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (pu2009=u20090.0009), but not in team A (pu2009=u20090.464). The control situation showed no difference between teams and study periods. Interpretation:u2002We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.

Enhanced glucocorticoid sensitivity of cytokine release from circulating leukocytes stimulated with lipopolysaccharide in healthy male smokers

Smoking is a strong cardiovascular risk factor that promotes inflammation. The source of elevated pro-inflammatory cytokines in the circulation of smokers is not fully understood. We investigated the release of pro-inflammatory cytokines from circulating leukocytes stimulated with lipopolysaccharide (LPS) and its inhibition by glucocorticoids in smokers and non-smokers. Ninety-three middle-aged apparently healthy men were categorized as smokers (> 10 cigarettes/day; n = 41) or life-long non-smokers (n = 52). Peripheral cortisol was assessed from overnight urine. C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha were measured in plasma. LPS-stimulated interleukin (IL)-6 and TNF-alpha release from harvested circulating leukocytes were assessed using an in vitro whole blood assay with and without co-incubation of increasing concentrations of either dexamethasone or hydrocortisone. Glucocorticoid sensitivity was defined as the concentration of glucocorticoids required that inhibits LPS-stimulated cytokine release by 50%. Smokers had higher CRP levels (p = .005) and a trend for higher basal TNF-alpha levels (p < .07), and they also showed lower IL-6 and TNF-alpha release after LPS-stimulation than non-smokers (ps < .001). While peripheral cortisol concentration showed no significant group difference, inhibition of LPS-stimulated leukocyte IL-6 and TNF-alpha release by either glucocorticoid was enhanced in smokers as compared to non-smokers (ps < .022). The finding suggests that, in spite of a low-grade systemic inflammation, smokers have decreased LPS-stimulated cytokine release from circulating leukocytes and greater glucocorticoid sensitivity of this cytokine release than non-smokers. Circulating leukocytes unlikely contribute to the elevated pro-inflammatory cytokine levels in the blood of smokers.

Reduced glucocorticoid sensitivity of monocyte interleukin-6 release in male employees with high plasma levels of tumor necrosis factor-α

Cytokine production by monocytes plays a key role in atherosclerosis. In vitro, preincubation of whole blood with tumor necrosis factor (TNF)-alpha regulates interleukin (IL)-6 release from monocytes stimulated with lipopolysaccharide (LPS). We investigated whether plasma levels of TNF-alpha would also relate to LPS-stimulated monocyte IL-6 production and the inhibitory effect of a glucocorticoid on this process. 224 middle-aged men were assigned to three groups according to tertiles of plasma levels of TNF-alpha. Subjects in the highest tertile (high TNF-alpha, n = 75) were compared to those in the lowest (low TNF-alpha, n = 74) and medium tertile (medium TNF-alpha, n = 75), respectively. In vitro monocyte IL-6 release following lipopolysaccharide (LPS)-stimulation was assessed with and without coincubation with incremental doses of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL-6 release by 50%. Subjects with high TNF-alpha showed more IL-6 release after LPS-stimulation than those with low TNF-alpha (p =.011). Monocyte glucocorticoid sensitivity was lower in subjects with high levels of TNF-alpha than in subjects with low (p =.014) and with medium (p =.044) levels of TNF-alpha. Results held significance when a set of classic cardiovascular risk factors was controlled for. Our findings suggest that elevated plasma levels of TNF-alpha might enhance LPS-stimulated IL-6 release from circulating monocytes. Such a mechanism might contribute to exaggerated monocyte cytokine release in vivo to any LPS-like danger signal such as related to an infection or cellular stress thereby promoting atherosclerosis.