Does Anxiety Affect Survival in Patients with Coronary Heart Disease?

INTRODUCTION: Behavioral and physiological risk factors worsen the prognosis of coronary heart disease (CHD). Anxiety is known to be a psychological predictor of CHD. In this study, we investigated whether this factor is associated with all-cause mortality in CHD patients in the long term. METHODS: We studied 180 patients (mean age 60.6 SD 9.2 years, 26% women) with CHD from the Berlin Anxiety Trial (BAT) and the Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) study. Their cardiac and psychological risk profile was represented by standardized procedures, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. Mortality outcomes were assessed using a community-based registry. RESULTS: Of 180 patients, we obtained information on all-cause mortality in 175 (96.7%) after a mean follow-up of 12.2 years (range 10.4-16.6 years). Of all participants, 54.4% had prior myocardial infarction, 95.3% had percutaneous transluminal coronary angioplasty and 22.2% had prior coronary artery bypass graft. Most of the patients (98.4%) had New York Heart Association class I and II, 25.6% had diabetes and 38.2% were smokers. Patients had a mean HADS anxiety score of 9.7 SD 4.1 at study entrance. We found the highest HADS anxiety quartile all-cause mortality in 14%, 30.2% in the middle quartiles and 58.7% in the lowest quartile (chi2 20.8, p = 0.001). Related to psychological mechanisms, a low level of anxiety, seemed to be a significant predictor of all-cause mortality. We found no advantage for patients who had received psychosocial therapy in terms of survival. CONCLUSION: These first data confirmed our hypothesis about the association of psychological risk factors with the long-term outcome of CAD patients. Future studies will clarify whether the severity of disease, age or a particular type of coping or denial mechanism are associated with the presented outcome in low-anxious patients.

Assessment of health-related quality of life in individuals with depressive symptoms: validity and responsiveness of the EQ-5D-3L and the SF-6D.

BACKGROUND: The EQ-5D and the SF-6D are examples of commonly used generic preference-based instruments for assessing health-related quality of life (HRQoL). However, their suitability for mental disorders has been repeatedly questioned. OBJECTIVE: To assess the responsiveness and convergent validity of the EQ-5D-3L and SF-6D in patients with depressive symptoms. METHODS: The data analyzed were from cardiac patients with depressive symptoms and were collected as part of the SPIRR-CAD (Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease) trial. The EQ-5D-3L and SF-6D were compared with the HADS (Hospital Anxiety and Depression Scale) and PHQ-9 (Patient Health Questionnaire) as disease-specific instruments. Convergent validity was assessed using Spearman's rank correlation. Effect sizes were calculated and ROC analysis was performed to determine responsiveness. RESULTS: Data from 566 patients were analysed. The SF-6D correlated considerably better with the disease-specific instruments (|rs|= 0.63-0.68) than the EQ-5D-3L (|rs|= 0.51-0.56). The internal responsiveness of the SF-6D was in the upper range of a small effect (ES: - 0.44 and - 0.47), while no effect could be determined for the EQ-5D-3L. Neither the SF-6D nor the EQ-5D-3L showed acceptable external responsiveness for classifying patients' depressive symptoms as improved or not improved. The ability to detect patients whose condition has deteriorated was only acceptable for the EQ-5D-3L. CONCLUSION: Overall, both the convergent validity and responsiveness of the SF-6D are better than those of the EQ-5D-3L in patients with depressive symptoms. The SF-6D appears, therefore, more recommendable for use in studies to evaluate interventions for this population.

Cortisol Awakening Reaction and Anxiety in Depressed Coronary Artery Disease Patients.

Disturbances of HPA axis functioning as represented by cortisol awakening reaction (CAR) belong to the mediating pathways linking psychosocial distress and cardiovascular risk. Both depression and anxiety have been confirmed as independent risk factors for coronary artery disease (CAD). However, data on anxiety and cortisol output in CAD patients are scarce. Based on previous data, we hypothesized that anxiety would be associated with higher cortisol output and a more pronounced morning increase in moderately depressed CAD patients. 77 patients (60 y, 79% male) underwent saliva sampling (+0, +30, +45, +60 min after awakening, midday and late-night sample). Anxiety was measured using the Hospital Anxiety and Depression Scale (HADS) and patients were grouped into anxious versus non anxious subjects based upon the recommended score (≥11). A repeated measures ANOVA yielded a significant time and quadratic time effect referring to the typical CAR. Anxious patients showed a significantly steeper 30 min increase, higher AUCi, lower waking and late-night cortisol levels. The steeper cortisol increase in the anxious group is in line with previous data and may be interpreted as a biological substrate of affect regulation. The lower basal and late-night levels coupled with greater AUCi mirror a more dynamic reactivity pattern compared to depressed subjects without anxiety.

Depression, anxiety, and vital exhaustion are associated with pro-coagulant markers in depressed patients with coronary artery disease - A cross sectional and prospective secondary analysis of the SPIRR-CAD trial.

INTRODUCTION: A hyper-coagulant state is a biological mechanism that triggers cardiac events in patients with coronary artery disease (CAD). Depressive symptoms and anxiety predict an unfavourable course of CAD. The SPIRR-CAD-RCT examined the effects of a psychological intervention and provided the opportunity to explore cross-sectional associations between indices of psychological strain and coagulation parameters, as well as prospective changes in depression scores and coagulation parameters. METHODS: In this secondary analysis, we investigated 253 CAD patients (194 male; age m 58.9, SD 8.3 yrs.) with mild to moderate depression (≥8 on the HADS-D) at baseline and at follow-up 18 months later: TF, fibrinogen, D-dimer, VWF, FVII and PAI-1 and the course of depression (HAM-D), vital exhaustion (VE) and anxiety scores (HADS-A) were examined by ANOVA in the total and younger age groups (≤ 60). RESULTS: HAM-D at baseline was correlated with TF (corr. R2 = 0.27; F = 9.31, p = 0.001). HADS anxiety was associated with fibrinogen (corr. R2.20; F = 7.27, p = 0.001). There was no detectable therapeutic effect on coagulation. Fibrinogen and VWF decreased within 18 months (time effect; p = 0.02; p = 0.04), as did HADS-D in both treatment groups (p < 0.001). Fibrinogen decreased more in patients ≤60 years with high VE compared to low VE (interaction time x group, p = 0.01). CONCLUSIONS: This is the first study to show an association between TF and depression. Coagulation parameters as potential mediators of CAD progression correlated cross-sectionally with depression and anxiety and prospectively with VE. Further studies should replicate these correlations in depressed and non-depressed CAD patients. ISRCTN: 76240576; clinicaltrials.gov.

Length Polymorphisms in the Angiotensin I-Converting Enzyme Gene and the Serotonin-Transporter-Linked Polymorphic Region Constitute a Risk Haplotype for Depression in Patients with Coronary Artery Disease.

Genetic variations affecting the course of depressive symptoms in patients with coronary artery disease (CAD) have not yet been well studied. Therefore, we set out to investigate whether distinct haplotypes of the two insertion/deletion polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) and the angiotensin I-converting enzyme (ACE) gene located on chromosome 17 can be identified as risk factors for trajectories of depression. Clinical and genotyping data were derived from 507 depressed CAD patients participating in the randomized, controlled, multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial, of whom the majority had an acute cardiac event before study inclusion. Depression scores on the Hospital Anxiety and Depression Scale (HADS) were assessed at baseline and at five follow-up time points up to 2 years after study entrance. At baseline, depression scores did not significantly differ between patients carrying the risk haplotype ACE D/D, 5-HTTLPR I/I (n = 46) and the non-risk haplotypes (n = 461, 10.9 ± 2.7 versus 10.4 ± 2.5, p = 0.254). HADS-depression scores declined from study inclusion during the first year irrespective of the genotype. At each follow-up time point, HADS-depression scores were significantly higher in ACE D/D, 5-HTTLPR I/I carriers than in their counterparts. Two years after study inclusion, the mean HADS depression score remained 1.8 points higher in patients with the risk haplotype as compared to subjects not carrying this haplotype (9.9 ± 4.2 versus 8.1 ± 4.0, p = 0.009). In summary, the presence of the ACE D/D, 5-HTTLPR I/I haplotype may be a vulnerability factor for comorbid depressive symptoms in CAD patients.

Longitudinal relationship between B-type natriuretic peptide and anxiety in coronary heart disease patients with depression.

OBJECTIVE: Patients with coronary heart disease (CHD) suffer from physical limitations, but also from psychological distress. Natriuretic peptides may be involved in the neurobiological processes that modulate psychological adaptation, as they are increased in heart disease and seem to have an anxiolytic-like function. Longitudinal data on this association are scarce. METHODS: To assess the relationship between NT-proBNP and anxiety (Hospital Anxiety and Depression Scale (HADS)), we used secondary data from a multicenter trial from baseline to 24 months. Patients (N = 308, 80.8% male, mean age 60.1 years) had stable CHD and moderate levels of depression (HADS ≥8). RESULTS: Multiple linear regression adjusted for age, sex, BMI, and physical functioning revealed NT-proBNP as a significant predictor for anxiety at baseline, 1, 6, 12, 18, and 24 months (all p < .05). Linear mixed model analysis with the six anxiety measures as level-1 variable and NT-proBNP as fixed factor revealed a significant time*NT-proBNP interaction (t(1535.99) = -2.669, p = .01) as well as a significant time*NT-proBNP*sex interaction (t(1535.99) = 3.277, p = .001), when NT-proBNP was dichotomized into lowest vs. the three highest quartiles. CONCLUSION: Our results indicate a stable negative association of baseline NT-proBNP with anxiety over two years. In men and women, different pathways modulating this relationship appear to be in effect. Female patients with very low NT-proBNP levels, despite their cardiac disease, show persistently higher levels of anxiety compared to women with higher levels of NT-proBNP and compared to men. Trial name: A Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD). TRIAL REGISTRATION: www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576.

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.

Somatic and sociodemographic predictors of depression outcome among depressed patients with coronary artery disease - a secondary analysis of the SPIRR-CAD study.

BACKGROUND: Depressive symptoms are common in patients with coronary artery disease (CAD) and are associated with an unfavourable outcome. Establishing prognostic patient profiles prior to the beginning of mental health care may facilitate higher efficacy of targeted interventions. The aim of the current study was to identify sociodemographic and somatic predictors of depression outcome among depressed patients with CAD. METHODS: Based on the dataset of the multicentre SPIRR-CAD randomised controlled trial (n = 570 patients with CAD and ≥ 8 points on the Hospital Anxiety and Depression Scale (HADS)), 141 potential sociodemographic and somatic predictors of the change in the HADS-D depression score from baseline to 18-month-follow-up were derived in two different ways. We screened for univariable association with response, using either analysis of (co)variance or logistic regression, respectively, both adjusted for baseline HADS-D value and treatment group. To guard against overfitting, multivariable association was evaluated by a linear or binomial (generalised) linear model with lasso regularisation, a machine learning approach. Outcome measures were the change in continuous HADS-D depression scores, as well as three established binary criteria. The Charlson Comorbidity Index (CCI) was calculated to assess possible influences of comorbidities on our results and was also entered in our machine learning approach. RESULTS: Higher age (p = 0.002), unknown previous myocardial infarction (p = 0.013), and a higher heart rate variability during numeracy tests (p = .020) were univariably associated with a favourable depression outcome, whereas hyperuricemia (p ≤ 0.003), higher triglycerides (p = 0.014), NYHA class III (p ≤ 0.028), state after resuscitation (p ≤ 0.042), intake of thyroid hormones (p = 0.007), antidiabetic drugs (p = 0.015), analgesic drugs (p = 0.027), beta blockers (p = 0.035), uric acid drugs (p ≤ 0.039), and anticholinergic drugs (p = 0.045) were associated with an adverse effect on the HADS-D depression score. In all analyses, no significant differences between study arms could be found and physical comorbidities also had no significant influence on our results. CONCLUSION: Our findings may contribute to identification of somatic and sociodemographic predictors of depression outcome in patients with CAD. The unexpected effects of specific medication require further clarification and further research is needed to establish a causal association between depression outcome and our predictors. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00705965 (registered 27th of June, 2008). www.isrctn.com ISRCTN76240576 (registered 27th of March, 2008).

Gender differences in psychosocial outcomes of psychotherapy trial in patients with depression and coronary artery disease.

INTRODUCTION: The biological and psychosocial risk profile differs between women and men with coronary artery disease (CAD). Depressive symptoms and Vital Exhaustion (VE) predict an unfavourable course of CAD. The secondary analysis of the SPIRR-CAD trial offered the possibility to examine gender as exposure variable of the clinical and psychological situation at baseline and in a variety of psychosocial measures as outcomes. METHODS: In this trial, 450 men (78.9%) and 120 women (21.1%) with CAD (age ≤ 75 y), with mild to moderate depression (scoring ≥8 on the HADS), were randomized to usual care with or without a stepwise psychotherapy intervention. Beside clinical measures exhaustion and other indicators of depressive symptoms were collected at baseline and 18-month follow up. RESULTS: Men had more signs and symptoms of heart disease at baseline, whereas women had higher psychosocial burden (e.g. negative affect). Women were more likely to live alone, had lower educational levels and employment rates and higher levels of depression and exhaustion. The psychotherapy intervention differed as a function of gender: In women, VE decreased from 29.4 ±â€¯8.1 to 22.1 ±â€¯11.7 in the intervention group (IG) and from 29.2 ±â€¯8.2 to 25.1 ±â€¯11.3 in the control group (CG). In men VE decreased from 23.3 + -10.8 to 21.2 ±â€¯9.7 in the IG and from 23.6 ±â€¯10.7 to 19.3 ±â€¯11.3 in the CG (time x intervention x gender; F = 4.97; p = .026). DISCUSSION: Women had a higher psychosocial burden than men. VE compared to other rating instruments of depressive symptoms suggested a stronger response to the intervention in women. VE may help to understand gender differences in psychotherapeutic treatment studies of CAD. ISRCTN: 76240576; clinicaltrials.gov.

Associations of NT-proBNP and parameters of mental health in depressed coronary artery disease patients.

Natriuretic peptides (NP) are involved in the regulation of blood pressure and blood volume, and are elevated in patients with coronary artery disease (CAD). They are used as markers for illness severity, but their role in mental health is not well understood. Recently, A-type NP (ANP) has been associated with reduced anxiety in studies on cardiac patients; however, this study is the first to assess this effect for B-type NP (BNP) and for further dimensions of well-being and mental health. Depression, anxiety, and distress are more common in CAD patients than in the general population and are most likely not only influenced by psychological adaptation but also by neurobiological processes. We used baseline N-terminal proBNP (NT-proBNP) samples and psychometric assessments of 529 at least mildly depressed (Hospital Anxiety and Depression Scale, depression score ≥ 8) CAD patients from the multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial. Psychosocial status was assessed using standardized self-rating questionnaires on anxiety, depression, coping with illness, vital exhaustion, type D personality, and quality of life. Separate linear regression models for each psychometric scale revealed significant negative correlations of NT-proBNP with anxiety, depression, vital exhaustion, depressive coping, and negative affectivity. Moreover, patients with higher levels of NT-proBNP experienced less bodily pain and had a better self-rated mental health, despite worse physical functioning. Linear regression adjusted for age, sex, and physical functioning (Short Form Health Survey [SF-36]) revealed NT-proBNP to be a significant predictor for all tested measures of the patients' psychosocial status. These results indicate that NT-proBNP is not only positively associated with greater disease severity in mildly to moderately depressed CAD patients but also with better psychosocial status and mental well-being. Possible mechanisms of this effect are discussed.

The relationship between attachment orientations and the course of depression in coronary artery disease patients: A secondary analysis of the SPIRR-CAD trial.

OBJECTIVE: The relationship between attachment orientations and the recovery from depressive symptoms in patients diagnosed with coronary artery disease (CAD) with and without a psychotherapeutic intervention was examined in this study. METHODS: In a multicenter trial of 570 depressed CAD patients (SPIRR-CAD), assigned to usual care plus either a stepwise psychotherapy intervention or one information session, 522 patients provided attachment data at baseline. Attachment was measured with the Relationship Scales Questionnaire (RSQ), yielding four attachment orientations. The primary outcome was change in Hospital Anxiety and Depression Scale depression (HADS-D) scores from baseline to follow-up at 18 months. Secondary outcomes were HADS-D scores at 1, 6, 12, and 24 months. RESULTS: Independent of treatment assignment, attachment was related to change in depression at 18 months (p < 0.01) with secure attachment resulting in a significant reduction (-2.72, SE = 0.27) in depression compared to dismissive-avoidant (-1.51, SE = 0.35, p = 0.040) and fearful-avoidant (-0.65, SE = 0.61, p = 0.012) attachment. Patients with anxious-preoccupied attachment showed changes similar to secure attachment (-2.01, SE = 0.47). An explorative subgroup analysis across all assessment time points revealed patients with a dismissive-avoidant attachment benefitted from psychotherapy (average mean difference = 0.93, SE = 0.47, p = 0.048). CONCLUSION: Attachment played an important role for improvement in depressive symptoms. Only dismissive-avoidant patients seemed to benefit from the intervention. The lack of improvement in fearful-avoidant patients shows a need for specific interventions for this group. TRIAL REGISTRATION: www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576.

Socioeconomic factors in coronary artery disease - Results from the SPIRR-CAD study.

Low socio-economic status (SES) has been associated with an increased coronary risk in Western countries. All stress experiences are more pronounced in low SES patients with stress emanating from problems with family, job, or money. The SPIRR-CAD study offered an excellent opportunity to examine these risk factors in German speaking mildly and medium depressed patients. In the SPIRR CAD study, a German multi centre randomized clinical trial of 450 male and 120 female coronary patients, we examined the standard and psychosocial risk factor profiles in relation to SES, as assessed by educational level. All differences in risk factors between low and high SES were in the inverse direction. Of standard risk factors, only smoking was socially graded and more common in low SES. Of psychosocial factors and emotions, exhaustion showed the strongest and most consistent inverse social gradient, but also anger, anxiety and depression were socially graded. The findings suggest that in German patients, as in other national groups, social gradients in CHD risk are considerable. They can be ascribed to both psychosocial and to standard risk factors. In the present two years follow-up, the prospective significance of psychological and social risk factors was analyzed showing that emotional factors played an important role, in that low and high SES patients differed in the expected direction. However, the differences were not statistically significant and therefore firm conclusions from follow up were not possible. TRIAL REGISTRATION: ISRCTN 76240576; NCT00705965.

Prevalence of mental disorders among depressed coronary patients with and without Type D personality. Results of the multi-center SPIRR-CAD trial.

OBJECTIVE: Type D personality, as with formal mental disorders, is linked to increased mortality in coronary heart disease (CHD). Our aim was to determine the prevalence of mental disorders among depressed CHD patients with and without Type D personality. METHODS: Depressive symptoms (HADS, HAM-D), Type D personality (DS-14) and mental disorders based on DSM-IV (SCID I and II) were assessed. Results were calculated by Kruskal-Wallis tests, Fisher's exact tests and logistic regression analyses. RESULTS: 570 CHD patients were included (age 59.2±9.5years; male 78.9%, HADS-D depression 10.4±2.5; HAM-D 11.3±6.6; Type D 60.1%). 84.8% of patients with Type D personality and 79.3% of non-Type D patients suffered from at least one mental disorder (p=0.092), while 41.8% of Type D positives and 27.8% of Type D negatives had at least two mental disorders (p=0.001). Patients with Type D personality significantly more often had social phobia [odds ratio (95% confidence interval): 3.79 (1.1 to 13.12); p=0.035], dysthymia [1.78 (1.12 to 2.84); p=0.015], compulsive [2.25 (1.04 to 4.86); p=0.038] or avoidant [8.95 (2.08 to 38.49); p=0.003] personality disorder. CONCLUSIONS: Type D personality among depressed CHD patients is associated with more complex and enduring mental disorders. This implies higher treatment demands. TRIAL REGISTRATION: ISRCTN 76240576; NCT00705965.

Affective Responses in Different Stages of Anorexia Nervosa: Results from a Startle-reflex Paradigm.

OBJECTIVE: There is an evolving debate about pathological affective responses in patients with anorexia nervosa (AN). We examined startle responses in different stages of AN. METHODS: We applied a startle reflex paradigm with standardized visual stimuli (International Affective Pictures System; food and body pictures) in 64 female participants (17 acute AN, 16 chronically ill AN, 15 long-term recovered AN, 16 healthy controls). We measured subjective ratings of valence and anxiety, and electromyographic startle responses. RESULTS: Participants with acute and chronic AN displayed the same subjective valence ratings to affective stimuli but showed less startle reactivity to affective pictures (F(6, 116) = 2.75, p = .02) compared with healthy control. Food pictures were rated as more unpleasant and higher anxiety provoking by currently ill AN (F(3, 59) = 3.32, p=.03). DISCUSSION: We observed diverging subjective and psychophysiological reactions in different stages of AN. Psychophysiological methods can help to attain a more comprehensive understanding of biological alterations in the long-term course of AN. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

A Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD): Results of an Observer-Blinded, Multicenter, Randomized Trial in Depressed Patients With Coronary Artery Disease.

BACKGROUND: Depression predicts adverse prognosis in patients with coronary artery disease (CAD), but previous treatment trials yielded mixed results. We tested the hypothesis that stepwise psychotherapy improves depressive symptoms more than simple information. METHODS: In a multicenter trial, we randomized 570 CAD patients scoring higher than 7 on the Hospital Anxiety and Depression Scale-depression subscale to usual care plus either one information session (UC-IS) or stepwise psychotherapy (UC-PT). UC-PT patients received three individual psychotherapy sessions. Those still depressed were offered group psychotherapy (25 sessions). The primary outcome was changed in the Hospital Anxiety and Depression Scale-depression scores from baseline to 18 months. Preplanned subgroup analyses examined whether treatment responses differed by patients' sex and personality factors (Type D). RESULTS: The mean (standard deviation) depression scores declined from 10.4 (2.5) to 8.7 (4.1) at 18 months in UC-PT and from 10.4 (2.5) to 8.9 (3.9) in UC-IS (both p < .001). There was no significant group difference in change of depressive symptoms (group-by-time effect, p = .90). Preplanned subgroup analyses revealed no differences in treatment effects between men versus women (ptreatment-by-sex interaction = .799) but a significant treatment-by-Type D interaction on change in depressive symptoms (p = .026) with a trend for stronger improvement with UC-PT than UC-IS in Type D patients (n = 341, p = .057) and no such difference in improvement in patients without Type D (n = 227, p = .54). CONCLUSIONS: Stepwise psychotherapy failed to improve depressive symptoms in CAD patients more than UC-IS. The intervention might be beneficial for depressed CAD patients with Type D personality. However, this finding requires further study. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00705965; www.isrctn.com ISRCTN76240576.

Heart Rate Variability during Inpatient Psychosomatic Treatment - A Naturalistic Observational Study.

OBJECTIVES: We tested the hypothesis that inpatient psychosomatic treatment would improve both psychological distress and autonomic dysfunction, indexed as heart rate variability (HRV). METHODS: 135 patients (mean age 47.2 years, 68.1% women) were enrolled. The most frequent diagnoses were somatoform disorders, adjustment disorders, major depression, eating disorders, and anxiety disorders.Mean duration of treatment was 21.8 ± 7.3 days. Complete HRV data were available on 105 patients. RESULTS: At the beginning of the treatment, psychological distress correlated with the low frequency/ high frequency ratio of HRV, indicating a shift of autonomic balance towards sympathetic predominance. Following treatment, psychological distress had improved, but parasympathetic activity was even lower. Tricyclic antidepressant use was associated with an increase in heart rate. No other associations between antidepressant use and autonomic function were observed. CONCLUSIONS: Reductions of psychological distress may not be reflected by improved autonomic function. Studies on interventions that may improve both psychological distress and autonomic dysfunction are desirable.

Pneumogastric (Vagus) Nerve Activity Indexed by Heart Rate Variability in Chronic Pain Patients Compared to Healthy Controls: A Systematic Review and Meta-Analysis.

BACKGROUND: A large body of scientific literature derived from experimental studies emphasizes the vital role of vagal-nociceptive networks in acute pain processing. However, research on vagal activity, indexed by vagally-mediated heart rate variability (vmHRV) in chronic pain patients (CPPs), has not yet been summarized. OBJECTIVES: To systematically investigate differences in vagus nerve activity indexed by time- and frequency-domain measures of vmHRV in CPPs compared to healthy controls (HCs). STUDY DESIGN: A systematic review and meta-analysis, including meta-regression on a variety of populations (i.e., clinical etiology) and study-level (i.e., length of HRV recording) covariates. SETTING: Not applicable (variety of studies included in the meta-analysis). METHODS: Eight computerized databases (PubMed via MEDLINE, PsycNET, PsycINFO, Embase, CINAHL, Web of Science, PSYNDEX, and the Cochrane Library) in addition to a hand search were systematically screened for eligible studies based on pre-defined inclusion criteria. A meta-analysis on all empirical investigations reporting short- and long-term recordings of continuous time- (root-mean-square of successive R-R-interval differences [RMSSD]) and frequency-domain measures (high-frequency [HF] HRV) of vmHRV in CPPs and HCs was performed. True effect estimates as adjusted standardized mean differences (SMD; Hedges g) combined with inverse variance weights using a random effects model were computed. RESULTS: CPPs show lower vmHRV than HCs indexed by RMSSD (Z = 5.47, P < .0001; g = -0.24;95% CI [-0.33, -0.16]; k = 25) and HF (Z = 4.54, P < .0001; g = -0.30; 95% CI [-0.44, -0.17]; k = 61).Meta-regression on covariates revealed significant differences by clinical etiology, age, gender, and length of HRV recording. LIMITATIONS: We did not control for other potential covariates (i.e., duration of chronic pain, medication intake) which may carry potential risk of bias. CONCLUSION(S): The present meta-analysis is the most extensive review of the current evidence on vagal activity indexed by vmHRV in CPPs. CPPs were shown to have lower vagal activity, indexed by vmHRV, compared to HCs. Several covariates in this relationship have been identified. Further research is needed to investigate vagal activity in CPPs, in particular prospective and longitudinal follow-up studies are encouraged.

Short-term effects of espresso coffee on heart rate variability and blood pressure in habitual and non-habitual coffee consumers--a randomized crossover study.

OBJECTIVE: Coffee is one of the most widely consumed beverages worldwide. Aim of this study was to investigate short-term effects of espresso coffee on heart rate variability (HRV), a marker of vagal activity, in healthy habitual and non-habitual coffee consumers. METHODS: Seventy-seven healthy subjects (38 habitual and 39 non-habitual coffee consumers, 74% women, mean age 26.97 ± 6.88 years) took part in three laboratory sessions in a randomized order. In condition 1, subjects consumed espresso; in condition 2, subjects consumed decaffeinated espresso; and in condition 3, subjects consumed warm water. HRV and blood pressure were assessed at rest before and after ingestion of the respective beverage. RESULTS: HRV was significantly increased after consumption of caffeinated espresso, decaffeinated espresso, or water, indicating increased vagal activity in the course of the experiments. In the habitual coffee consumers, the increase in vagally mediated HRV was significantly lower after consumption of decaffeinated espresso compared to caffeinated espresso. Increases of systolic blood pressure were only found in the non-habitual consumers. CONCLUSION: We found no evidence for specific short-term effects of caffeinated espresso on vagal activity in healthy subjects. Instead, consumption of decaffeinated espresso inhibited vagal activity in habitual consumers. This may be explained by an attempt of the organism to establish a sympathovagal equilibrium comparable to that after caffeine consumption. In the absence of caffeine-induced sympathetic activation, this may have been achieved by relative vagal withdrawal.

Autonomic effects of suggestive placebo interventions to increase or decrease blood pressure: a randomized controlled trial in healthy subjects.

OBJECTIVE: Placebo effects on pain and other subjective parameters are well-established, but the evidence for placebo effects on autonomic functions is scarce. Our randomized-controlled trial aimed to investigate autonomic responses after a suggestive placebo intervention intended to increase or decrease blood pressure (BP). METHODS: 92 healthy subjects inhaled a placebo spray with the prior suggestion that it contained an effective drug to either increase or decrease BP, or the information that a placebo was administered (controls). BP, heart rate, stroke volume, peripheral resistance, heart rate variability and skin conductance level were monitored 30min before and after placebo administration. The expected and the subjectively perceived drug effect were measured by means of visual analog scales. RESULTS: We found no statistically significant differences between the groups with respect to BP, heart rate, stroke volume, total peripheral resistance and heart rate variability responses to the verbal suggestions. Skin conductance response was more pronounced in the BP decrease group compared with controls (p=0.04), but this finding might be due to chance, given the multiple tests. Within the total study sample, BP, total peripheral resistance, low frequency power of heart rate variability and skin conductance were significantly higher after the placebo spray independent of the associated suggestions. Subjects in the BP increase and BP decrease condition had higher ratings of the expected and the subjectively perceived drug effect compared with controls (all p<0.05). CONCLUSION: We found no evidence that specific verbal suggestions during placebo interventions affect BP in healthy subjects.

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.