Coronary microvascular function in male physicians with burnout and job stress: an observational study.

BACKGROUND: As a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that is at least as high as that of other professionals. This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events. METHODS: Thirty male physicians with clinical burnout and 30 controls without burnout were included. Burnout was assessed with the Maslach Burnout Inventory and job stress with the effort-reward imbalance and overcommitment questionnaire. All participants underwent myocardial perfusion positron emission tomography to quantify endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function. Burnout and job stress were regressed on coronary flow reserve (primary outcome) and two additional measures of coronary microvascular function in the same model while adjusting for age and body mass index. RESULTS: Burnout and job stress were significantly and independently associated with endothelium-dependent microvascular function. Burnout was positively associated with coronary flow reserve, myocardial blood flow response, and hyperemic myocardial blood flow (r partial = 0.28 to 0.35; p-value = 0.008 to 0.035). Effort-reward ratio (r partial = - 0.32 to - 0.38; p-value = 0.004 to 0.015) and overcommitment (r partial = - 0.30 to - 0.37; p-value = 0.005 to 0.022) showed inverse associations with these measures. CONCLUSIONS: In male physicians, burnout and high job stress showed opposite associations with coronary microvascular endothelial function. Longitudinal studies are needed to show potential clinical implications and temporal relationships between work-related variables and coronary microvascular function. Future studies should include burnout and job stress for a more nuanced understanding of their potential role in cardiovascular health.

Association between global sleep quality and coronary microvascular function in male physicians with occupational burnout.

OBJECTIVE: Occupational burnout has been associated with an increased risk of coronary heart disease, although the mechanisms involved are elusive. We investigated whether poor global sleep quality is associated with impaired coronary microvascular function in male physicians, a professional group at increased risk for burnout. METHODS: Study participants were 30 male physicians with clinical burnout and 30 controls without burnout defined by the Maslach Burnout Inventory. Global sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function were quantified with myocardial perfusion positron emission tomography. In multivariable analyses, the interaction between burnout and the PSQI global score was regressed on measures of coronary microvascular function, adjusting for age, body mass index, physical activity, alcohol consumption, and main effects of burnout and PSQI score. RESULTS: The prevalence of poor sleepers (PSQI score > 5) was 40% in the burnout group and 10% in the control group. Adjusting for covariates, burnout-by-global PSQI score interactions were observed for myocardial blood flow (MBF) at rest (r partial = -.30, p = .025), endothelium-dependent coronary flow reserve (r partial = -.26, p = .062), MBF response (r partial = -.30, p = .028), and hyperemic MBF (r partial = -.34, p = -.012). The global PSQI score was inversely associated with these MBF measures in the burnout group relative to the control group. No significant interactions emerged for endothelium-independent MBF. CONCLUSIONS: In male physicians with occupational burnout, poor global sleep quality was associated with reduced endothelium-dependent coronary microvascular function, suggesting a mechanism by which burnout may affect cardiovascular health.

Do Hypertensive Men Spy With an Angry Little Eye? Anger Recognition in Men With Essential Hypertension - Cross-sectional and Prospective Findings.

BACKGROUND: Higher trait anger has inconsistently been associated with hypertension and hypertension development, but social context in terms of recognition of other persons' anger has been neglected in this context. PURPOSE: Here, we investigated anger recognition of facial affect and trait anger in essential hypertensive and normotensive men in addition to prospective associations with blood pressure (BP) increases. METHODS: Baseline assessment comprised a total of 145 participants including 57 essential hypertensive and 65 normotensive men who were otherwise healthy and medication-free. Seventy-two eligible participants additionally completed follow-up assessment 3.1 (±0.08 SEM) years later to analyze BP changes over time. We assessed emotion recognition of facial affect with a paradigm displaying mixed facial affect of two morphed basic emotions including anger, fear, sadness, and happiness. Trait anger was assessed with the Spielberger trait anger scale. RESULTS: Cross-sectionally, we found that with increasing BP, hypertensive men overrated anger displayed in facial expressions of mixed emotions as compared to normotensive men (ps ≤ .019) while there were no differences in trait anger (p = .16). Prospectively, the interaction between mean anger recognition and trait anger independently predicted BP increases from baseline to follow-up (ps ≤ .043), in that overrating displayed anger predicted future BP increases only if trait anger was high. CONCLUSIONS: Our findings indicate an anger recognition bias in men with essential hypertension and that overrating displayed anger in combination with higher trait anger seems to predict future BP increases. This might be of clinical relevance for the development and progression of hypertension and cardiovascular disease.

The Role of Norepinephrine and α-Adrenergic Receptors in Acute Stress-Induced Changes in Granulocytes and Monocytes.

OBJECTIVE: Acute stress induces redistribution of circulating leucocytes in humans. Although effects on lymphocytes as adaptive immune cells are well understood, the mechanisms underlying stress effects on granulocytes and monocytes as innate immune blood cells are still elusive. We investigated whether the stress hormone norepinephrine (NE) and α-adrenergic receptors (α-ADRs) may play a mediating role. METHODS: In a stress study, we cross-sectionally tested 44 healthy men for associations between stress-induced NE increases and simultaneous granulocyte and monocyte cell count increases, as measured immediately before and several times after the Trier Social Stress Test. In a subsequent infusion study, 21 healthy men participated in three different experimental trials with sequential infusions of 1- and 15-minute duration with varying substances (saline as placebo, the nonspecific α-ADR blocker phentolamine [2.5 mg/min], and NE [5 µg/min]): trial 1 = saline+saline, trial 2 = saline+NE, trial 3 = phentolamine+NE. Granulocyte and monocyte cell numbers were assessed before, immediately after, 10 minutes, and 30 minutes after infusion procedures. RESULTS: In the stress study, higher NE related to higher neutrophil stress changes (ß = .31, p = .045, R change = .09), but not epinephrine stress changes. In the infusion study, saline+NE induced significant increases in neutrophil (F(3/60) = 43.50, p < .001, η = .69) and monocyte (F(3/60) = 18.56, p < .001, η = .48) numbers compared with saline+saline. With phentolamine+NE, neutrophil (F(3/60) = 14.41, p < .001, η = .42) and monocyte counts (F(2.23/44.6) = 4.32, p = .016, η = .18) remained increased compared with saline+saline but were lower compared with saline+NE (neutrophils: F(3/60) = 19.55, p < .001, η = .494, monocytes: F(3/60) = 2.54, p = .065, η = .11) indicating partial mediation by α-ADRs. Trials did not differ in eosinophil and basophil count reactivity. CONCLUSIONS: Our findings suggest that NE-induced immediate increases in neutrophil and monocyte numbers resemble psychosocial stress effects and can be reduced by blockade of α-ADRs.

Macrophage Superoxide Anion Production in Essential Hypertension: Associations With Biological and Psychological Cardiovascular Risk Factors.

OBJECTIVE: Essential hypertension is an important risk factor for coronary artery disease and its underlying process atherosclerosis, but involved mechanisms are not fully understood. Both macrophages and superoxide anions have been proposed to play a major role in the pathogenesis of atherosclerosis. In the present study, we investigated whether macrophages of individuals with hypertension show higher nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide anion production compared with normotensive individuals. Furthermore, we examined associations between macrophage superoxide anion production and the psychological factors depression and chronic stress independent from hypertension status. METHODS: We studied 30 hypertensive (mean [standard deviation] = 48.7 [2.4] years) and 30 age-matched normotensive men (mean [standard deviation] = 48.6 [2.4] years). We assessed macrophage superoxide anion production using the WST-1 assay. The assay is based on the chemical reduction of the cell-impermeative tetrazolium salt WST-1 by superoxide anions that are produced by activated human ex vivo isolated monocyte-derived macrophages. We further evaluated whether chronic stress or depressive symptom severity was associated with macrophage superoxide anion production. All analyses were adjusted for potential confounders. RESULTS: Individuals with hypertension showed higher superoxide anion production compared with normotensive individuals (F(1,58) = 11.56, p = .001). Complementary analyses using mean arterial blood pressure as a continuous measure revealed that higher mean arterial pressure correlated significantly with higher WST-1 reduction (ß = .38, p = .003, ΔR = .145). These results remained significant when controlling for potential confounding influences. Chronic stress was related to higher WST-1 reduction scores, but this association was not statistically significant (ß = .24, p = .067, ΔR = .053); depression levels were not significantly associated with WST-1 reduction scores (p = .24). CONCLUSIONS: Our results indicate higher macrophage superoxide anion production in individuals with hypertension compared with normotensive individuals. This may suggest a mechanism underlying cardiovascular risk with hypertension.

Stress-induced modulation of NF-κB activation, inflammation-associated gene expression, and cytokine levels in blood of healthy men.

Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines, but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms. We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level. Forty-five healthy men were randomly assigned to either a stress or control group. While the stress group underwent an acute psychosocial stress task, the second group participated in a non-stress control condition. We repeatedly measured before and up to 120min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, whole-blood mRNA levels of NF-κB, its inhibitor IκBα, and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6, and the anti-inflammatory cytokine IL-10. We also repeatedly measured plasma levels of IL-1ß, IL-6, and IL-10. Compared to non-stress, acute stress induced significant and rapid increases in NF-κB-BA and delayed increases in plasma IL-6 and mRNA of IL-1ß, IL-6, and IκBα (p's<.045). In the stress group, significant increases over time were also observed for NF-κB mRNA and plasma IL-1ß and IL-10 (p's<.055). NF-κB-BA correlated significantly with mRNA of IL-1ß (r=.52, p=.002), NF-κB (r=.48, p=.004), and IκBα (r=.42, p=.013), and marginally with IL-6 mRNA (r=.31, p=.11). Plasma cytokines did not relate to NF-κB-BA or mRNA levels of the respective cytokines. Our data suggest that stress induces increases in NF-κB-BA that relate to subsequent mRNA expression of pro-inflammatory, but not anti-inflammatory cytokines, and of regulatory-cytoplasmic-proteins. The stress-induced increases in plasma cytokines do not seem to derive from de novo synthesis in circulating blood cells.

Increased daytime and awakening salivary free aldosterone in essential hypertensive men.

Background: While aldosterone plays an important role in blood pressure regulation, its role in essential hypertension (EHT) remains unclear. Here, we systematically investigated the secretion of biologically-active free aldosterone in saliva in response to awakening (AldAR) and during the day (AldDay) in EHT compared to normotensive controls (NT). Methods: In 30 men with EHT and 30 age-matched NT, AldAR saliva samples were collected immediately after awakening and 15, 30, 45, and 60 min thereafter and AldDay samples were collected from 08:30-22:00 h on two consecutive days. Results: Over the course of the day, men with EHT had higher repeated AldDay levels compared to NT (p = .002) with higher concentrations in the morning hours (p's ≤ .047), a steeper decline over the course of the day (p's ≤ .018), and similar concentrations in the evening (p's ≥ .21). Regarding AldAR, we observed higher concentrations in EHT at awakening (p = .017) and borderline higher concentrations at 15 min (p = .086). No differences were found 30-60 min after awakening (p's ≥ .34). Analyses with repeated and aggregated AldAR levels resulted in borderline significantly higher free aldosterone in EHT (p's ≤ .077). Complementary analyses confirmed linear associations between higher blood pressure and higher AldAR and AldDay levels. Conclusions: Our data point to elevated salivary free aldosterone secretion in EHT over the course of the day, particularly in the morning hours. As the free aldosterone fraction is considered biologically active, our data may point to a biological mechanism underlying EHT.

Validation of the German Purpose in Life Questionnaire (PLQ) in a healthy population and patients with cardiovascular disease.

In this cross-sectional study, a German translation of the subscale "Purpose in Life" (PLQ) from the Scales of Psychological Well-being (SPWB) was validated in a representative sample of participants from healthy and cardiovascular populations. The main objectives were to assess the reliability, convergent, and discriminant validity using a large and representative sample (N = 466 healthy sample, N = 247 patients with an implanted cardioverter-defibrillator (ICD), N = 70 patients with a cardiovascular disease (CVD)). The findings indicated that the German PLQ is a reliable and valid measure of positive psychological well-being, showing a positive correlation with health-related quality of life, optimism, and positive affect. In turn, the PLQ score was significantly and negatively correlated with depressive symptom severity, anxiety, pessimism, and negative affect, while being distinct from these constructs. The comparability of the measurement properties of the German PLQ with the original English version further supports the validity of the translation. Additionally, the unidimensional structure of the German version mirrored that of the English PLQ. As this study used a large and representative sample, it provides the most up-to-date normative population value for the subscale of the SPWB. Moreover, this study represents the first known exploration of the questionnaire in a cardiovascular sample, revealing relationships between health-related quality of life, optimism, positive affect, and the German PLQ. However, in patients with ICD, the positive correlation between the PLQ and the physical component of the SF-12 did not reach significance. Despite these valuable findings, future research to enhance the understanding of the PLQ and its implications is warranted.

Cross-sectional study on the impact of adverse childhood experiences on coronary flow reserve in male physicians with and without occupational burnout.

OBJECTIVE: Physicians face documented challenges to their mental and physical well-being, particularly in the forms of occupational burnout and cardiovascular disease. This study examined the previously under-researched intersection of early life stressors, prolonged occupational stress, and cardiovascular health in physicians. METHODS: Participants were 60 practicing male physicians, 30 with clinical burnout, defined by the Maslach Burnout Inventory, and 30 non-burnout controls. They completed the Adverse Childhood Experiences (ACE) Questionnaire asking about abuse, neglect and household dysfunctions before the age of 18, and the Perceived Stress Scale to rate thoughts and feelings about stress in the past month. Endothelium-independent (adenosine challenge) coronary flow reserve (CFR) and endothelium-dependent CFR (cold pressor test) were assessed by positron emission tomography-computed tomography. The segment stenosis score was determined by coronary computed tomography angiography. RESULTS: Twenty-six (43%) participants reported at least one ACE and five (8%) reported ≥4 ACEs. A higher ACEs sum score was associated with lower endothelium-independent CFR (r partial (rp) = -0.347, p = .01) and endothelium-dependent CFR (rp = -0.278, p = .04), adjusting for age, body mass index, perceived stress and segment stenosis score. In exploratory analyses, participants with ≥4 ACEs had lower endothelium-independent CFR (rp = -0.419, p = .001) and endothelium-dependent CFR (rp = -0.278, p = .04), than those with <4 ACEs. Endothelium-dependent CFR was higher in physicians with burnout than in controls (rp = 0.277, p = .04). No significant interaction emerged between burnout and ACEs for CFR. CONCLUSION: The findings suggest an independent association between ACEs and CFR in male physicians and emphasize the nuanced relationship between early life stressors, professional stress, and cardiovascular health.

Differential associations of sex and age with changes in HRQoL during outpatient cardiac rehabilitation.

INTRODUCTION: Cardiovascular diseases (CVD) represent the world's leading cause of death. Health-related quality of life (HRQoL) is a widely applied concept of patients' perceived health and is directly linked to CVD morbidity, mortality, and re-hospitalization rates. Cardiac rehabilitation (CR) improves both cardiovascular outcomes and HRQoL. Regrettably, CR is still underutilized, especially in subgroups like women and elderly patients. The aim of our study was to investigate the predictive potential of sex and age on change of HRQoL throughout outpatient CR. METHODS: 497 patients of outpatient CR were retrospectively assessed from August 2015 to September 2019 at the University Hospital Zurich. A final sample of 153 individuals with full HRQoL data both at CR entry and discharge was analyzed. HRQoL was measured using the 36-Item Short Form Survey (SF-36) with its physical (PCS) and mental (MCS) component scale. In two-factorial analyses of variance, we analyzed sex- and age-specific changes in HRQoL scores throughout CR, adjusting for psychosocial and clinical characteristics. Age was grouped into participants over and under the age of 65. RESULTS: In both sexes, mean scores of physical HRQoL improved significantly during CR (p <.001), while mean scores of mental HRQoL improved significantly in men only (p =.003). Women under the age of 65 had significantly greater physical HRQoL improvements throughout CR, compared with men under 65 (p =.043) and women over 65 years of age (p =.014). Sex and age did not predict changes in mental HRQoL throughout CR. CONCLUSIONS: Younger women in particular benefit from CR with regard to their physical HRQoL. Among older participants, women report equal improvements of physical HRQoL than men. Our results indicate that sex- and age-related aspects of HRQoL outcomes should be considered in CR.

Cortisol Reactivity to Acute Psychosocial Stress in Physician Burnout.

BACKGROUND: Physician burnout, characterized by chronic job-related stress leading to emotional exhaustion, depersonalization, and reduced personal accomplishment. This cross-sectional study investigates cortisol reactivity in male physicians with burnout compared to healthy controls during an acute psychosocial stress test. METHODS: Sixty male physicians (30 burnout, 30 healthy controls) participated between September 2019 and December 2021 to investigate the impact of burnout on cardiovascular health. Salivary cortisol levels were measured before and after a Trier Social Stress Test (TSST). Burnout was assessed with the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Covariates included age, BMI, and physical activity. Data were analyzed using repeated measures analysis and area under the curve analysis. RESULTS: Male physicians with burnout exhibited significantly greater cortisol reactivity during the TSST, notably post-stress to 15 min post-stress. Emotional exhaustion correlated with reduced cortisol increase from pre-stress and smaller post-stress to 15- and 45-min declines. DISCUSSION: Findings suggest heightened cortisol reactivity in male physicians with burnout, possibly reflecting initial chronic stress stages. This study highlights the necessity for long-term research on cortisol's influence on cardiovascular health and stress responses across diverse groups. CONCLUSIONS: The findings contribute to comprehending physiological responses in burnout-afflicted physicians, emphasizing cortisol reactivity's pivotal role in stress-related research and its potential health implications, particularly within the burnout context.

Long-Term Follow-Up of HRQoL up to Six Years after Outpatient Phase-II Cardiac Rehabilitation.

Background: Low health-related quality of life (HRQoL) is associated with adverse cardiovascular outcomes in coronary heart disease (CHD) patients. Cardiac rehabilitation (CR) improves HRQoL; however, evidence on long-term HRQoL changes after CR, and their predictors, is missing. Methods: A total of 153 patients with complete HRQoL data in the short-form (SF)-36 Health Survey at CR entry, discharge and follow-up were included. Using linear mixed-effects regression models for repeated time measurements, we examined predictors of follow-up HRQoL, including age and clinical characteristics. Results: Both physical (t = -5.66, p < 0.001) and mental (t = -2.06, p = 0.040) HRQoL improved significantly from CR entry to discharge, with improvements remaining stable over a mean follow-up of four years (range 2.4-6.1). Better functional capacity (6MWT) at CR entry predicted better physical HRQoL (t = 5.50, p < 0.001) and, with a trend, better mental HRQoL (t = 1.92, p = 0.056) at follow-up. A psychiatric diagnosis at CR entry predicted better mental HRQoL at follow-up (t = 3.85, p < 0.001). Conclusions: Improvements in HRQoL during CR remain stable during long-term follow-up. Levels of functional capacity appear to be relevant to both physical and mental HRQoL at follow-up.

Taking appreciation to heart: appreciation at work and cardiovascular risk in male employees.

Introduction: While perceived appreciation at work has been associated with self-reported health and wellbeing, studies considering biological health markers are lacking. In this study, we investigated whether appreciation at work would relate to coronary heart disease (CHD) risk as well as the specificity of this proposed association. Methods: Our study comprised a total of 103 male participants, including apparently healthy, medication-free, non-smoking men in the normotensive to hypertensive range (n = 70) as well as medicated hypertensive and CHD patients (n = 33). CHD risk was assessed by blood pressure [mean arterial pressure (MAP)], the diabetes marker glycated hemoglobin A1c (HbA1c), blood lipids [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio], coagulation activity (D-dimer and fibrinogen), and inflammation [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)]. Perceived appreciation at work, as well as potentially confounding psychological factors (social support, self-esteem, and work strain due to a lack of appreciation), were measured by self-report questionnaires. Results: We found higher appreciation at work to relate to lower overall composite CHD risk (p's ≤ 0.011) and, in particular, to lower MAP (p's ≤ 0.007) and lower blood lipids (p's ≤ 0.031) in medication-free participants as well as all participants. This overall association was independent of confounding factors, including related psychological factors (p's ≤ 0.049). Discussion: Our findings indicate that appreciation at work might be an independent health-promoting resource in terms of CHD risk. Implications include that encouraging appreciation at work may help reduce the development and progression of CHD.

Mindfulness Is Associated with Lower Depression, Anxiety, and Post-Traumatic Stress Disorder Symptoms and Higher Quality of Life in Patients with an Implantable Cardioverter-Defibrillator-A Cross-Sectional Study.

Several studies suggested the efficacy of dispositional mindfulness and mindfulness-based interventions in reducing anxiety and depression in cardiovascular diseases. However, data on the impact of mindfulness on the psychological well-being of patients with an implantable cardioverter-defibrillator (ICD) are scarce. In this study, 422 patients with an ICD were prospectively recruited. Logistic regression was applied to determine associations between dispositional mindfulness (Freiburg Mindfulness Inventory), depression (Patient Health Questionnaire-8), anxiety (Generalized Anxiety Disorder-7 scale), and post-traumatic stress disorder (PTSD) symptoms (Post-Traumatic Stress Diagnostic Scale), adjusting for age, sex, educational status, number of ICD shocks after ICD implantation, and physical activity. The PROCESS regression path analysis modelling tool was used to identify indirect mediating effects of dispositional mindfulness on depression, anxiety, and PTSD symptoms and quality of life (QoL; EuroQol group 5-dimension questionnaire). Participants presented high baseline QoL (mean 1.06 to 1.72) and medium-high mindfulness scores (mean 40.85 points). Higher mindfulness scores were associated with lower levels of anxiety (OR 0.90, 95% CI 0.86 to 0.95, 0.001), depression (OR 0.93, 95% CI 0.88 to 0.98, p = 0.006), and PTSD symptoms (OR 0.94, 95% CI 0.89 to 0.98, p = 0.011). Furthermore, greater mindfulness partially mediated the relationship between anxiety (indirect effect 0.10, 95% CI 0.02 to 0.21), depression (indirect effect 0.08, 95% CI 0.01 to 0.17), or PTSD (indirect effect 0.04, 95% CI 0.01 to 0.17) as independent variables and the QoL as the dependent variable. This study suggests that greater dispositional mindfulness is associated with less anxiety, depression, and PTSD symptoms. Mindfulness might also increase the QoL in ICD patients by mitigating the impact of those with psychological distress.

Association of positive psychological well-being with circulating inflammatory markers: A systematic review and meta-analysis.

Accumulating evidence shows a protective effect of positive psychological well-being (PPWB) on health outcomes. However, the underlying mechanisms remain poorly understood. One pathway relates to enhanced immune functioning (Boehm, 2021). The aim of this project was to conduct a systematic review and meta-analysis of the association between PPWB and circulating inflammatory biomarkers and determine the magnitude of this association. After examining 748 references, 29 studies were included. Results from over 94'700 participants revealed a significant association between PPWB and reduced levels of interleukin (IL)- 6 (r = -0.05; P < .001) and C-reactive protein (CRP) (r = -0.06; P < .001) with a heterogeneity of I2 = 31.5% and I2 = 84.5%, respectively. Only the association of PPWB with CRP was independent of co-variates included in the individual studies (r = -0.04; P = .027). The findings of this systematic review and meta-analysis suggest that PPWB is associated with lower levels of inflammatory biomarkers IL-6 and CRP in the circulation. Such relationships with inflammatory biomarkers may partly explain positive effects of PPWB on health.

Sex and age as predictors of health-related quality of life change in Phase II cardiac rehabilitation.

AIMS: Cardiac rehabilitation (CR) not only improves cardiovascular outcomes, but also health-related quality of life (HRQOL). Unfortunately, CR is still underutilized, especially among women and older patients. Aim of this study was to highlight age- and sex-specific effects of inpatient CR on HRQOL. METHODS AND RESULTS: From 2012 to 2018, 18 459 patients were prospectively assessed in six Swiss CR clinics. Of these, we retrospectively analysed a final sample of 8286 patients with a mean (standard deviation) age of 67.8 (11.3) in men and 72.2 (11.3) in women. HRQOL was measured at CR entry and discharge. In multivariable analyses, sex- and age-specific changes in HRQOL throughout CR were estimated, adjusting for baseline HRQOL and clinical characteristics. Participants of both sexes improved significantly (P < 0.001) in all domains of HRQOL during CR. Women reported significantly lower social (P < 0.001) and emotional (P < 0.001) HRQOL than men at CR entry. Female sex predicted greater improvement in social (F = 19.63, P < 0.001), emotional (F = 27.814, P < 0.001), and physical HRQOL (F = 20.473, P < 0.001). In a subgroup of n = 2632 elderly patients (>75 years), female sex predicted greater changes in emotional (F = 15.738, P < 0.001) and physical (F = 6.295, P = 0.012), but not in social HRQOL. CONCLUSION: Women report poorer HRQOL at CR entry compared with men, but in turn particularly benefit from CR in this regard. Our results indicate that sex- and age-specific needs of patients should be considered.

Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk.

Background: Coronary heart disease (CHD) and its major risk factor hypertension have both been associated with altered activity of the hypothalamus-pituitary-adrenal (HPA)-axis but the biological mechanisms underlying prospective associations with adverse disease outcomes are unclear. We investigated diurnal HPA-axis activity in CHD-patients, hypertensive (HT) and healthy normotensive men (NT) and tested for prospective associations with biological CHD risk factors. Methods: Eighty-three male CHD-patients, 54 HT and 54 NT men repeatedly measured salivary cortisol over two consecutive days. Prospective CHD risk was assessed by changes between baseline and follow-up in the prothrombotic factors D-dimer and fibrinogen, the pro-inflammatory measures interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and acute phase protein C-reactive protein (CRP), as well as blood lipids in terms of total cholesterol (tChol)/high-density-lipoprotein cholesterol (HDL)-ratio. We aggregated coagulation and inflammatory measures to respective indices. Results: The groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η2 p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η2 p=.03,f=0.18), with similarly lower overall dayCort and CAR in CHD-patients and HT, as compared to NT. The groups differed further in cortisol at awakening (p=.015,η2 p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η2 p=.04,f=0.20) with steepest slopes in HT (p´s≤.039), although in part not independent of confounders. Lower aggregated dayCort and CAR in terms of area-under-the-curve (AUC) independently predicted increases in future overall CHD risk (AUCdayCort: p=.021,η2 p=.10,f=0.33;AUCCAR: p=.028,η2 p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUCdayCort: p=.017,ΔR 2= 0.12;AUCCAR: p=.082). Conclusion: We found evidence for an HPA-axis hypoactivity in CHD and HT with lower diurnal HPA-axis activity predicting increases in cardiovascular risk as evidenced by increases in circulating levels of biomarkers of atherothrombotic risk. Down-regulation of basal HPA-axis activity may contribute to the pathogenesis of atherosclerosis and thrombosis in CHD via effects on coagulation.

Sympathetic nervous system responses to acute psychosocial stress in male physicians with clinical burnout.

BACKGROUND: Occupational burnout has been associated with an increased risk of cardiovascular disease, with sympathetic nervous system (SNS) dysfunction as one explanation. This study examined the effects of burnout on responses of SNS activity measures to acute psychosocial stress in male physicians, a population at risk for burnout. METHODS: Study participants were 60 male physicians, 30 with clinical burnout, assessed with the Maslach Burnout Inventory, and 30 without burnout (controls). All participants underwent the 15-min Trier Social Stress Test. Heart rate, blood pressure, salivary alpha-amylase, and plasma levels of epinephrine (EPI) and norepinephrine were assessed pre-stress, immediately post-stress, and 15 min and 45 min post-stress. RESULTS: Physicians with burnout and controls differed in EPI changes over time, controlling for age, job stress and anxiety symptoms (F (3,147) = 5.18, p = .002 for 'Time by Group' interaction; η2p = .096). Burnout was associated with a smaller increase in EPI from pre-stress to immediately post-stress (r(54) = -.40, p = .004). The emotional exhaustion dimension of burnout was a significant driver of this effect. The area under the curve with respect to increase in EPI was also smaller in the burnout group (F (1,49) = 6.06, p = .017, η2p = .110). Group differences were not significant for the other SNS activity measures. CONCLUSIONS: Burnout may be linked to dysfunction of the sympathoadrenal medullary (SAM) system, when exposed to acute psychosocial stress. In keeping with the allostatic load concept, an insufficient SAM stress response in burnout could potentially contribute to cardiovascular disease.

Longitudinal association between positive affect and blood lipids in patients following acute myocardial infarction.

OBJECTIVE: Unfavorable blood lipid profiles are robust risk factors in predicting atherosclerotic disease. Studies have shown that positive affect (PA) is associated with a favorable lipid profile. However, longitudinal studies regarding the course of PA and lipid profiles in myocardial infarction (MI) patients are lacking. Therefore, the aim of this study was to prospectively explore the association between PA and blood lipid levels across three inv estigations over 12 months following acute MI. METHODS: Patients following an acute MI were examined at hospital admission (n = 190), and at 3 months (n = 154) and 12 months (n = 106) thereafter. Linear mixed effect regression models were used to evaluate the relation between PA, assessed with the Global Mood Scale, and blood lipid levels. Potential confounding variables were controlled for in the analysis. RESULTS: Higher PA was significantly associated with higher high-density lipoprotein cholesterol (HDL-C) levels and a lower total cholesterol (TC)/HDL-C ratio over time, independent of demographic factors, indices of cardiac disease severity, comorbidity, medication use, health behaviors, serum cortisol and negative affect (p≤0.040). No association was found between PA and the two blood lipids low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG). CONCLUSIONS: Positive affect was independently associated with HDL-C levels and the TC/HDL-C ratio in patients up to 1 year after MI. The findings support a potential role of PA for cardiovascular health through an association with a favorable blood lipid profile.