Transitioning from having no metabolic abnormality nor obesity to metabolic impairment in a cohort of apparently healthy adults.

INTRODUCTION: The global prevalence of metabolic syndrome and its association with increased morbidity and mortality has been rigorously studied. However, the true prevalence of "metabolic health", i.e. individuals without any metabolic abnormalities is not clear. Here, we sought to determine the prevalence of "metabolically healthy" individuals and characterize the "transition phase" from metabolic health to development of dysfunction over a follow-up period of 5 years. METHODS: We included 20,507 individuals from the Tel Aviv Sourasky Medical Center Inflammation Survey (TAMCIS) which comprises apparently healthy individuals attending their annual health survey. A second follow-up visit was documented after 4.8 (± 0.6) years. We defined a group of metabolically healthy participants without metabolic abnormalities nor obesity and compared their characteristics and change in biomarkers over time to participants who developed metabolic impairment on their follow-up visit. The intersections of all metabolic syndrome components and elevated high sensitivity C-reactive protein (hs-CRP) were also analyzed. RESULTS: A quarter of the cohort (5379 individuals, (26.2%) did not fulfill any metabolic syndrome criteria during their baseline visit. A total of 985 individuals (12.7% of returning participants) developed metabolic criteria over time with hypertension being the most prevalent component to develop among these participants. Individuals that became metabolically impaired over time demonstrated increased overlap between metabolic syndrome criteria and elevated hs-CRP levels. The group that became metabolically impaired over time also presented higher delta values of WBC, RBC, liver biomarkers, and uric acid compared with participants who were consistently metabolically impaired. LDL-C (low-density lipoprotein cholesterol) delta levels were similar. CONCLUSIONS: Roughly one-quarter of apparently healthy adults are defined as "metabolically healthy" according to current definitions. The transition from health to metabolic dysfunction is accompanied with active inflammation and several non-metabolic syndrome biomarkers. Aggressive screening for these biomarkers, blood pressure and hs-CRP might help identify apparently healthy individuals at increased risk of developing metabolic syndrome over time.

Fear and C-reactive protein cosynergize annual pulse increases in healthy adults.

Recent international terror outbreaks notably involve long-term mental health risks to the exposed population, but whether physical health risks are also anticipated has remained unknown. Here, we report fear of terror-induced annual increases in resting heart rate (pulse), a notable risk factor of all-cause mortality. Partial least squares analysis based on 325 measured parameters successfully predicted annual pulse increases, inverse to the expected age-related pulse decline, in approximately 4.1% of a cohort of 17,380 apparently healthy active Israeli adults. Nonbiased hierarchical regression analysis among 27 of those parameters identified pertinent fear of terror combined with the inflammatory biomarker C-reactive protein as prominent coregulators of the observed annual pulse increases. In comparison, basal pulse primarily depended on general physiological parameters and reduced cholinergic control over anxiety and inflammation, together indicating that consistent exposure to terror threats ignites fear-induced exacerbation of preexisting neuro-immune risks of all-cause mortality.

Weakened Cholinergic Blockade of Inflammation Associates with Diabetes-Related Depression.

Emerging evidence demonstrates association of depression with both immune malfunctioning and worsened course of diverse aging-related diseases, but there is no explanation for the pathway(s) controlling this dual association. Here, we report that in post-reproductive and evolutionarily -blind" years, depression may weaken pathogen-host defense, compatible with the antagonistic pleiotropy hypothesis. In 15,532 healthy volunteers, depression scores associated with both inflammatory parameters and with increased circulation cholinesterase activities, implicating debilitated cholinergic blockade of inflammation as an underlying mechanism; furthermore, depression, inflammation and cholinesterase activities all increased with aging. In the entire cohort, combined increases in inflammation and the diabetic biomarker hemoglobin A1c associated with elevated depression. Moreover, metabolic syndrome patients with higher risk of diabetes showed increased cholinesterase levels and pulse values, and diabetic patients presented simultaneous increases in depression, inflammation and circulation cholinesterase activities, suggesting that cholinergic impairment precedes depression. Our findings indicate that dysfunctioning cholinergic regulation weakens the otherwise protective link between depression and pathogen-host defense, with global implications for aging-related diseases.

Self-rated health is associated with elevated C-reactive protein even among apparently healthy individuals.

BACKGROUND: A single self-rated health (SRH) assessment is associated with clinical outcome and mortality, but the biological process linking SRH with immune status remains incompletely understood. OBJECTIVES: To examine the association between SRH and inflammation in apparently healthy individuals. METHODS: Our analysis included 13,773 apparently healthy individuals attending the Tel Aviv Sourasky Medical Center for periodic health examinations. Estimated marginal means of the inflammation-sensitive biomarkers [i.e., highly sensitive C-reactive protein (hs-CRP) and fibrinogen] for the different SRH groups were calculated and adjusted for multiple potential confounders including risk factors, health behavior, socioeconomic status, and coexistent depression. RESULTS: The group with the lowest SRH had a significantly higher atherothrombotic profile and significantly higher conentrations of all inflammation-sensitive biomarkers in both genders. Hs-CRP was found to differ significantly between SRH groups in both genders even after gradual adjustments for all potential confounders. Fibrinogen differs significantly according to SRH in males only, with low absolute value differences. CONCLUSIONS: A valid association exists for apparently healthy individuals of both genders between inflammation-sensitive biomarker levels and SRH categories, especially when comparing levels of hs-CRP. Our findings underscore the importance of assessing SRH and treating it like other markers of poor health.

The role of personality in predicting repeat participation in periodic health screening.

OBJECTIVE: Drawing on the Five-Factor Model of personality, the aim of the present study was to find out which personality traits predict health maintenance behaviors, reflected in routine participation in health screenings, over and above objective and subjective health status. METHOD: Participants were 2,803 employed individuals (61% men), free of background diseases, who underwent a routine health examination and were subsequently notified whether they were healthy or at risk. These participants were invited to repeat the examination within the next few years, as is medically recommended. RESULTS: Logistic and negative binomial regressions were used to predict participants' odds of returning for a second examination, within the next 7 years, as well as the number of consecutive visits, while controlling for sociodemographic factors, objective and subjective health, and length of follow-up. We found that both endpoints were positively predicted by Conscientiousness and negatively predicted by Extraversion and Openness. The association between Neuroticism and these endpoints followed a bell-shaped curve (i.e., individuals high or low in Neuroticism were less likely to return). CONCLUSIONS: The present findings suggest that personality traits should be taken into consideration in the planning and implementation of health-promoting interventions.

Burnout and risk of coronary heart disease: a prospective study of 8838 employees.

OBJECTIVE: Burnout is a negative affective state consisting of emotional exhaustion, physical fatigue, and cognitive weariness symptoms. This study was designed to evaluate prospectively the association between burnout and coronary heart disease (CHD) incidence and to test the possibility that this association is nonlinear. METHODS: Participants were 8838 apparently healthy employed men and women, aged 19 to 67 years, who came for routine health examinations at the Tel Aviv Sourasky Medical Center. They were followed up for 3.4 years on average. Burnout was measured by the Shirom-Melamed Burnout Measure. CHD incidence was defined as a composite of acute myocardial infarction, diagnosed ischemic heart disease, and diagnosed angina pectoris. RESULTS: During follow-up, we identified 93 new cases of CHD. Baseline levels of burnout were associated with an increased risk of CHD, after adjustment for various risk factors (hazard ratio = 1.41; 95% confidence interval = 1.08-1.85). In addition, we observed a significant threshold effect of burnout on CHD incidence. Participants who scored high on burnout (scores in the upper quintile of the Shirom-Melamed Burnout Measure scores distribution) had a higher risk (hazard ratio = 1.79; 95% confidence interval = 1.05-3.04) of developing CHD on follow-up compared with others. CONCLUSIONS: Burnout is an independent risk factor for future incidence of CHD. Individuals with high levels of burnout (upper quintile) have a significantly higher risk of developing CHD compared with those with low levels of burnout.

The relationships between self-rated health and serum lipids across time.

BACKGROUND AND PURPOSE: We studied the hypothesized effects of changes in self-rated health (SRH) on subsequently assessed changes in the levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides (TRI), separately for men and women. We also investigated the reverse causation hypothesis, expecting the initial changes in the levels of serum lipids to predict subsequently assessed changes in SRH levels. METHODS: We used a longitudinal design and controlled for possible confounders known to be precursors of both SRH and the above three serum lipids. Participants were apparently healthy men (N = 846) and women (N = 378) who underwent a routine health check at three points of time (T1, T2, and T3); T1 and T3 were on the average 40 and 44 months apart for the men and women, respectively. RESULTS AND CONCLUSIONS: For the men, relative to T1 SRH, an increase in T2 SRH was associated with an increase in the T3 HDL-C levels relative to T2 HDL-C and with a decrease in the T3 TRI levels relative to T2 TRI. For the women, initial changes in the SRH levels did not predict follow-up changes in either of the lipids. For both genders, the reverse causation hypothesis, expecting the T1-T2 change in each of the serum lipids to predict T2-T3 change in SRH, was not supported. For the men, there is support for the hypothesis that the effects of SRH on morbidity and mortality, found by past meta-analytic studies, could be mediated by serum lipids.

Is the PHQ-9 a unidimensional measure of depression? A 58,272-participant study.

The PHQ-9 has become a measure of reference in depression research and clinical practice. However, the issue of the PHQ-9's unidimensionality has not been fully elucidated, and the usability of the PHQ-9's total score requires clarification. In this study, we examined the dimensionality, scalability, and monotonicity properties of the PHQ-9 as well as the scale's total-score reliability. We did so based on exploratory structural equation modeling (ESEM) bifactor analysis and Mokken scale analysis (MSA). We relied on a total of 58,272 participants (63% female; Mage = 43, SDage = 13) from 29 samples involving seven different countries (e.g., Germany, the U.S.) and five different languages (e.g., German, English). We found no concerning deviations from measurement invariance for our ESEM bifactor model, neither across samples nor across sexes, age groups, and languages. The PHQ-9 met the requirements for essential unidimensionality in the pooled sample and across sex-, age-, and language-based subsamples. In each case, the general factor was strong (e.g., factor loadings ranged from 0.725 to 0.893 in the pooled sample) and Omega Hierarchical values exceeded 0.900. The correlations between the general factor and the observed total scores were large (≥ 0.952). Our MSA, including multilevel MSA, revealed that the PHQ-9's scalability is satisfactory. No monotonicity violation was detected, suggesting that the scale's total score accurately orders respondents on the latent Depression variable. Total-score reliability was good. This study provides robust evidence that the PHQ-9 can be used as a unidimensional measure of depressive symptoms by researchers and practitioners. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Feeling vigorous and the risks of all-cause mortality, ischemic heart disease, and diabetes: a 20-year follow-up of healthy employees.

OBJECTIVE: To investigate prospectively the effects of vigor at work on the end points of mortality and the prevalence of ischemic heart disease (IHD) and diabetes. METHODS: We tested the hypothesized beneficial effects of feeling vigorous at work at baseline on the risks of all-cause mortality, IHD, and diabetes during a 20-year follow-up. Participants were healthy employees (n = 968) who underwent a routine health check at baseline. We calculated the risk of all-cause mortality, IHD, and diabetes, with days as the time scale, using the Cox proportional hazard model. In our analyses, we predicted the above end points by baseline vigor, age, gender, and educational level, adjusting for the physiological risk factors of total cholesterol, glucose, and body mass index, the behavioral risk factors of smoking, alcohol intake, and physical activity, and the psychological risk factors of depressive and anxiety symptoms. RESULTS: As hypothesized, we found that, after the above adjustments, baseline vigor decreased the risk of follow-up mortality by 26% (hazard ratio, 0.74; 95% confidence interval, 0.58-0.95) and the risk of diabetes by 17% (hazard ratio, 0.83; 95% confidence interval, 0.68-0.98). However, vigor did not have a significant effect on the risk of IHD. CONCLUSIONS: Independently of physiological, behavioral, and psychological risk factors, feeling vigorous at work protected the participants from diabetes and reduced their risk of mortality.

The effects of physical fitness and feeling vigorous on self-rated health.

OBJECTIVE: We prospectively studied the hypothesized beneficial effects of feeling vigorous and of objective physical fitness (gauged based on functional capacity) on subsequently assessed self-rated health (SRH), controlling for possible confounders known to be precursors of SRH and of our predictors. We also investigated the reverse-causation hypothesis that SRH predicts subsequent vigor and functional capacity. DESIGN: Participants were apparently healthy employees (N = 779) who underwent a routine health check at two points of time, Time 1 (T1) and Time 2 (T2), about 18 months apart. We used regression analysis, predicting T2 SRH by T1 SRH, the control variables, and T1vigor and functional capacity. MAIN OUTCOME MEASURES: Vigor was assessed using the Shirom-Melamed Vigor Measure; objective physical fitness was indicated by functional capacity following a treadmill exercise, and self-rated health was measured by a single item. RESULTS: As hypothesized, we found that the change in T2 SRH was positively predicted by T1 vigor, functional capacity, and their interactive term. Testing the reverse causation paths, we found that T1 SRH did not predict subsequent functional capacity and was a relatively weak predictor of subsequent vigor. CONCLUSION: The affective state of vigor and objectively assessed functional capacity interact to predict subsequent changes in self-rated health.

Depression and the metabolic syndrome: gender-dependent associations.

This study was designed to test the extent to which depressive symptoms are associated with the presence of the metabolic syndrome (MS) and each of its components, and whether these relationships are gender dependent. Participants were apparently healthy employed men (N=2,355) and women (N=1,525) who underwent a routine health check between the years 2003 and 2005. We used logistic regression analysis, predicting the MS by depressive symptoms, as assessed by the Patient Health Questionnaire, and the following control variables: age, education, smoking status, physical exercise, anxiety, and burnout. As hypothesized, we found that depression among women, but not men, was associated with a 1.94-fold risk of having the MS, and with an elevated risk of having two of its five components: elevated waist circumference (odds ratio, OR=2.23) and elevated glucose levels (OR=2.44). In addition, a positive trend was observed toward an association with the other three components: low high-density lipoprotein, hypertension, and elevated triglycerides. Among men depression was associated with elevated waist circumference only (OR=1.77). These findings suggest that especially among women, the association between depression and cardiovascular diseases might be linked to metabolic processes. If replicated in longitudinal studies, these findings may have important health-care policy implications with regard to depression management interventions.

Exposure to and fear of terror as predictors of self-rated health among apparently healthy employees.

The effects of exposure to terror on physical health were investigated by relating objective exposure to terror and fear of terror to self-rated health (SRH), a proxy measure of health status. Our respondents were apparently healthy (N=4,877, 38% women) adults who completed self-report questionnaires. Objective exposure was assessed by the number of terrorist attacks and their casualties in a respondent's urban area prior to her/his completion of the questionnaire. Using several alternative assessments, objective exposure to terror did not predict SRH for both the genders. As hypothesized, fear of terror negatively predicted SRH for both females and males (beta=-0.04, -0.05, respectively). The effects of subjective and objective exposure were not found to be more pronounced among women relative to men, thus disconfirming our hypotheses in this regard. Our findings suggest that living under continuous fear of terror may adversely influence physical health irrespective of objective exposure.

Burnout and risk of cardiovascular disease: evidence, possible causal paths, and promising research directions.

Burnout is characterized by emotional exhaustion, physical fatigue, and cognitive weariness, resulting from prolonged exposure to work-related stress. The authors review the accumulated evidence suggesting that burnout and the related concept of vital exhaustion are associated with increased risk of cardiovascular disease and cardiovascular-related events. The authors present evidence supporting several potential mechanisms linking burnout with ill health, including the metabolic syndrome, dysregulation of the hypothalamic-pituitary-adrenal axis along with sympathetic nervous system activation, sleep disturbances, systemic inflammation, impaired immunity functions, blood coagulation and fibrinolysis, and poor health behaviors. The association of burnout and vital exhaustion with these disease mediators suggests that their impact on health may be more extensive than currently indicated.

Burnout and risk of type 2 diabetes: a prospective study of apparently healthy employed persons.

OBJECTIVE: This prospective study was designed to test the extent to which the onset of type 2 diabetes in apparently healthy individuals was predicted by burnout, a unique affective response to combined exposure to chronic stressors. METHODS: The study participants were 677 employed men and women who were followed up for 3 to 5 years (mean = 3.6 years) for the onset of diagnosed type 2 diabetes. Burnout was assessed by the Shirom-Melamed Burnout Measure with its three subscales: emotional exhaustion, physical fatigue, and cognitive weariness. RESULTS: The burnout symptoms were remarkably consistent over the follow-up period irrespective of changes in place of work and in employment status. During the follow-up period, 17 workers developed type 2 diabetes. Logistic regression results indicated that burnout was associated with a 1.84-fold increased risk of diabetes (95% confidence interval [CI] = 1.19-2.85) even after adjusting for age, sex, body mass index, smoking, alcohol use, leisure time physical activity, initial job category, and follow-up duration. In a subsample of 507 workers, the relative risk of diabetes was found to be much higher after additional control for blood pressure levels (odds ratio = 4.32, 95% CI = 1.75-10.67), available only for this subsample. CONCLUSIONS: These findings suggest that chronic burnout might be a risk factor for the onset of type 2 diabetes in apparently healthy individuals.

Lack of significant effect of low doses of aspirin on the concentrations of C-reactive protein in a group of individuals with atherothrombotic risk factors and vascular events.

Atherothrombosis is associated with the presence of a microinflammatory response, usually monitored by the use of C-reactive protein (CRP) measurements. In the Physician Health Study it was suggested that individuals who benefit most from the treatment are those who have enhanced concentrations of this biomarker. The possibility was suggested that one of the mechanisms of action of aspirin in thrombotic prevention is through its anti-inflammatory properties in terms of reducing the concentration of CRP. We conducted a regression analysis in a cohort of 3888 apparently healthy individuals and those with atherothrombotic risk factors and vascular events, 370 of whom were under the treatment of low doses (

Values of high-sensitivity C-reactive protein in each month of the year in apparently healthy individuals.

The serum levels of high-sensitivity C-reactive protein were determined during a 12-month period. No seasonal variation was found in a group of 1,677 apparently healthy patients in whom the presence of clinically evident infection or inflammation was excluded by an appropriate questionnaire.

The association between burnout, depression, anxiety, and inflammation biomarkers: C-reactive protein and fibrinogen in men and women.

Following the demonstrated association of employee burnout or vital exhaustion with several risk factors for cardiovascular disease (CVD) and CVD risk, the authors investigated the possibility that one of the mechanisms linking burnout with CVD morbidity is microinflammation, gauged in this study by high-sensitivity C-reactive protein (hs-CRP) and fibrinogen concentrations. Their sample included 630 women and 933 men, all apparently healthy, who underwent periodic health examinations. The authors controlled for possible confounders including 2 other negative affective states: depression and anxiety. In women, burnout was positively associated with hs-CRP and fibrinogen concentrations, and anxiety was negatively associated with them. In men, depression was positively associated with hs-CRP and fibrinogen concentrations, but not with burnout or anxiety. Thus, burnout, depression, and anxiety are differentially associated with microinflammation biomarkers, dependent on gender.

Till stress do us part: On the interplay between perceived stress and communication network dynamics.

This study of perceived stress and communication networks fills 2 theoretical gaps in the literature: First, drawing predominantly on conservation of resource theory and faultline theory, we demonstrate the role of stress as an "engine of action" in network evolution. Second, we extend the stress literature to the interpersonal domain by arguing that others' levels of stress influence the individual's communication network, and this, in turn, changes his or her stress level. At 3 time points, we evaluated the communication ties and perceived stress in a unique field setting comprising 115 male participants (in 6 groups) performing group-based tasks. We introduce stochastic actor-based models for the coevolution of network ties and actor attributes, statistical models that enable causal inferences to be drawn regarding the interplay between dynamic networks and individual attributes. Using these models, we find that over time, individuals experiencing higher levels of perceived stress were less likely to create new communication ties and were more likely to maintain existing ties to others. Participants also tended to communicate with similarly stressed others. Such communication network dynamics further increased individuals' levels of perceived stress over time, leading to stress-related vicious cycles. We discuss organizational implications that relate to stress and network-related interventions.

Association of fear of terror with low-grade inflammation among apparently healthy employed adults.

OBJECTIVE: Based on evidence that psychological stress may induce a chronic inflammatory process, we hypothesized that the stress caused by chronic fear of terror may be associated with low-grade inflammation. This hypothesis was examined in employed men and women with the presence of low-grade inflammation measured by high sensitivity C-reactive protein (CRP). METHODS: Apparently healthy employed adults (N = 1153) undergoing periodic health check-ups in a tertiary hospital in Israel completed a questionnaire. Fear of terror (scored 1-5) was assessed by three items measuring the extent to which respondents have deep concern for personal safety, elevated tension in crowded places, and fear of terror strikes causing harm to one's self or one's family members. The main outcome measure was the presence or absence of an elevated CRP level (>3.0 mg/L). RESULTS: Women scored significantly higher on fear of terror compared with men (M = 2.16 vs. M = 1.68, respectively; p <.0001). Most of the study participants who scored high (4 or 5) on fear of terror, reported having experienced this feeling for 1 year or more. In women only, there was a positive association between fear of terror and risk of elevated CRP level (adjusted OR = 1.7, 95% CI 1.2-2.4) in a multivariate model adjusting for generalized anxiety, depressive symptoms, and potentially confounding demographic and biomedical variables. CONCLUSIONS: Chronic fear of terror in women, but not in men, is associated with elevated CRP levels, which suggests the presence of low-grade inflammation and a potential risk of cardiovascular disease.

Joint effect of chronic medical illness and burnout on depressive symptoms among employed adults.

OBJECTIVE: Chronic medical illnesses (CMIs) are prevalent in nearly half the working population and are associated with a two-fold risk for developing depression. Burnout is a chronic affective state comprised of symptoms of emotional exhaustion, physical fatigue, and cognitive weariness. It is an outcome of depletion of energetic resources resulting from prolonged exposure to work and life stresses. Building upon the Conservation of Resources theory (Hobfoll, 1989), this prospective study was designed to test the hypothesis that CMI interacts with burnout to facilitate the development of depressive symptoms. METHOD: Participants were 4,861 employed men and women, aged 19 to 67 years, who came for routine health examinations and were followed for 18 months on average. Forty-seven percent reported having one or more diagnosed CMIs. RESULTS: Burnout was found to predict an increase in depressive symptoms in apparently healthy individuals. Furthermore, the coexistence of burnout in employees with a CMI accelerates the process of developing depressive symptoms within a relatively short period. Burnout was also found to be associated with intensification of preexisting depressive symptoms in employees suffering from different chronic medical conditions (other than cancer), independent of medical comorbidities and other potent confounding variables. CONCLUSIONS: Among employees, coexistence of burnout and at least one CMI predicts an increase in depressive symptoms with time. Health care professionals should be made aware of such at-risk employees and follow and manage them closely.