Significance of psychosocial factors in cardiology: update 2018 : Position paper of the German Cardiac Society.

BACKGROUND: Psychosocial factors in cardiovascular diseases are increasingly acknowledged by patients, health care providers and payer organizations. Due to the rapidly increasing body of evidence, the German Cardiac Society has commissioned an update of its 2013 position paper on this topic. The German version was published in 2018 and the current manuscript is an extended translation of the original version. METHODS: This position paper provides a synopsis of the state of knowledge regarding psychosocial factors in the most relevant cardiovascular diseases and gives recommendations with respect to their consideration in clinical practice. RESULTS: Psychosocial factors such as low socioeconomic status, acute and chronic stress, depression, anxiety and low social support are associated with an unfavorable prognosis. Psychosocial problems and mental comorbidities should be assessed routinely to initiate targeted diagnostics and treatment. For all patients, treatment should consider age and gender differences as well as individual patient preferences. Multimodal treatment concepts should comprise education, physical exercise, motivational counseling and relaxation training or stress management. In cases of mental comorbidities, brief psychosocial interventions by primary care providers or cardiologists, regular psychotherapy and/or medications should be offered. While these interventions have positive effects on psychological symptoms, robust evidence for possible effects on cardiac outcomes is still lacking. CONCLUSIONS: For coronary heart disease, chronic heart failure, arterial hypertension, and some arrhythmias, there is robust evidence supporting the relevance of psychosocial factors, pointing to a need for considering them in cardiological care. However, there are still shortcomings in implementing psychosocial treatment, and prognostic effects of psychotherapy and psychotropic drugs remain uncertain. There is a need for enhanced provider education and more treatment trials.

Acute psychological stress increases peripheral blood CD3+CD56+ natural killer T cells in healthy men: possible implications for the development and treatment of allergic and autoimmune disorders.

Acute psychological stress has primarily been investigated regarding its effects on conventional lymphocytes such as natural killer (NK) cells and CD4(+) and CD8(+) T cells. However, it might be important to focus on more "specialized" lymphocyte subsets, playing a role, for instance, in allergic conditions and autoimmunity, to identify links between stress, the immune system and somatic diseases. Using flow cytometry we determined frequencies of circulating T helper (Th)1-type (CD226(+)) and Th2-type (CRTH2(+)) T cells, γδ T cells, conventional CD56(+) natural killer T (NKT) cells and invariant NKT cells (iNKT) in healthy young males (N = 31; median age 26 years) undergoing a laboratory computer-based stressor lasting 12 min. We found that acute psychological stress induced a prolonged increase in CD4(+) and CD8(+) T cells expressing a Th2 phenotype. We also detected an acute increase in CD4(-) and CD8(-) double negative γδ T cells. Finally, we found that the well-known increase in NK cells under stressful conditions was paralleled by a significant increase in numbers of conventional CD56(+) NKT cells. In contrast, numbers of iNKT was not altered by stress. This study adds further evidence to a psychoneuroimmunological model proposing that under stressful conditions certain lymphocyte subsets, including iNKT and less mature T cells, are retained in lymphoid tissues while antigen-experienced effector-type T cells with a Th2 phenotype, γδ T cells and conventional CD56(+) NKT cells are mobilized into the peripheral blood. We suggest that in the case of frequent stress exposure, this might result in the promotion of, for example, allergic conditions.

Anxiety as predictor of the cortisol awakening response in patients with coronary heart disease.

BACKGROUND: Anxiety is associated with worse outcomes in patients with coronary heart disease (CHD). A dysregulation of the HPA axis is a potential mechanism linking psychological factors and coronary disease. No study has yet investigated the relationship between anxiety and cortisol among patients with established CHD. PURPOSE: The aim of this study was to assess the association between anxiety and the cortisol awakening response in patients with CHD. METHOD: Four salivary cortisol samples were used to assess two measures of the cortisol awakening response (CAR) in 47 patients with established CHD. Anxiety was measured using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Higher anxiety values were associated with a higher total output of cortisol in the first hour after awakening (AUCg, area under the curve with respect to ground) (p = 0.04) and a nonsignificant trend towards a more pronounced increase (AUCi, area under the curve with respect to increase) (p = 0.08). In patients who had a history of myocardial infarction (MI), the cortisol output was lower compared to patients who had no previous MI (p = 0.02). In linear regression analyses, anxiety emerged as significant predictor of AUCg and AUCi after controlling for MI, ejection fraction (LVEF, left ventricular ejection fraction), and depression. CONCLUSIONS: Our results provide further indications for an association between anxiety and a dysregulation of the HPA axis. History of MI emerged as second predictor of cortisol output in the morning.

[C reactive protein in women with coronary heart disease and its association with depression]. / C-reaktives Protein bei Frauen mit koronarer Herzkrankheit und Zusammenhange mit Depressivitat.

OBJECTIVES: Depression is associated with increased risk and poor outcome of coronary heart disease (CHD), though the mechanisms are largely unknown. Low-grade inflammation offers a possible biological pathway, which has been confirmed in men but not in women. METHODS: We studied the association of C reactive protein (CRP), a biomarker of inflammation, with depressive symptoms in 292 women with CHD and 300 healthy age-matched controls, considering confounder variables (BMI, age, HDL cholesterol, triglycerides, menopausal status). CRP was measured by a high sensitivity assay. RESULTS: In the overall sample no significant association was found between depressive symptoms and CRP, whereas in the control group women with 2 or more versus 0-1 depressive symptoms showed heightened CRP (p = 0.005); there was no significant difference in CRP levels between CHD patients with 0-1 versus 2 or more depressive symptoms. Women with CHD had higher serum levels of CRP and more depressive symptoms than did controls. CONCLUSIONS: Contrary to men and healthy controls there was no link between CRP and depressive symptoms in women with CHD. More research is needed on how the harmful effects of depression are mediated, especially in women.

Low vagal tone is associated with impaired post stress recovery of cardiovascular, endocrine, and immune markers.

Reduced heart rate variability (HRV) and delayed blood pressure recovery are associated with increased cardiovascular risk. Besides this evident link, the vagus is thought to play an inhibitory role in the regulation of other allostatic systems, including inflammation and the hypothalamic-pituitary-adrenal (HPA) axis. However, human evidence is scarce. To further explore these associations and with special regard to the postulated mediating role of the vagus, we hypothesised that subjects with low vagal tone as indexed by reduced resting HRV would show impaired post-stress recovery of cardiovascular, endocrine and immune system markers involved in cardiovascular pathology. 44 healthy men underwent a standardised mental stress test. Besides continuous measurement of systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and HRV serum cortisol, tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured before, after, 20, and 60 min after stress. Low versus high HRV groups was defined by median split on resting HRV (RMSSD). The task elicited significant time effects for SBP, DBP, HR, HRV, cortisol, and TNF-alpha. Subjects with low baseline HRV showed almost no modulation of HRV coupled with overall reduced HRV levels, and impaired recovery of DBP, cortisol, and TNF-alpha. Confirming our hypothesis, low vagal tone was associated with impaired recovery of cardiovascular, endocrine, and immune markers in healthy males. The data support an inhibitory role of the vagus in the regulation of allostatic systems as described in the neurovisceral integration model. We posit reduced resting HRV as a risk marker for future cardiovascular and other stress-related disease.

Decrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor.

We have previously shown that acute psychological stress alerts the adaptive immune response causing an increase in antigen-experienced effector T cells in the peripheral blood. T regulatory cells (Tregs) play a central role in maintaining self-tolerance and controlling autoimmune responses. Here, we analyzed for the first time the behaviour of Tregs in the context of a stress-induced activation of the adaptive immune response. 31 healthy young males underwent a brief laboratory stressor and, in a crossover design, served as their own unstressed controls. We quantified effects of acute stress on CD4(+)FOXP3(+) T regulatory cells and other T cell subpopulations using flow cytometry. In addition, the expression of Treg-related effector molecules and stress hormone receptors were analyzed in the subjects' peripheral T cells. We confirmed our previous observation of a stress-induced decrease in CD45RA(+)CCR7(+) "naïve" and CD45RA(-)CCR7+ "central memory" T cells while CD45RA(-)-CCR7(-) "memory effector" and CD45RA(+)CCR7(-) "terminally differentiated" effector T cells remained stable or increased. Importantly, we found acute psychological stress to cause a concomitant decrease in CD4(+)FOXP3(+) Tregs and in CD4(+) T cells expressing Treg-related effector molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and latency associated peptide (LAP). Finally, we observed beta(1)-adrenergic and glucorticoid alpha receptors to be overexpressed in Tregs, suggesting that these molecules might mediate stress-related effects on Tregs. In conclusion, inhibiting components of the adaptive immune response, like Tregs, are down-regulated during a stress-induced activation of the adaptive immune response. In situations of chronic stress, this scenario might result in an exacerbation of inflammatory conditions such as autoimmune diseases.

Emotional irritation before mental stress is associated with enhanced peripheral norepinephrine.

Research suggests equivocal findings on associations of catecholamines and mood. Our study investigated the associations of emotional state, blood pressure and catecholamines in 55 healthy males undergoing mental stress. We especially checked the reported link between norepinephrine (NE) and emotional irritation. Blood pressure (SBP, DBP) and heart rate (HR) were continuously monitored. NE and epinephrine (EPI) were measured before, after, and 20 minutes after stress. Participants were divided into irritated versus non-irritated and anxious versus non-anxious subjects by median split on their baseline questionnaires. The task elicited significant cardiovascular, hormonal, and psychological stress responses. NE levels were significantly correlated with irritation before stress. Irritated subjects showed significantly higher DBP and NE than non-irritated subjects. The higher NE and DBP levels in the irritated participants suggest detrimental psycho-physiological interrelations promoting the development of stress-mediated cardiovascular diseases. Heightened emotional irritation before stress may be regarded as a psychological risk factor.