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.

Behavioral factors predict all-cause mortality in female coronary patients and healthy controls over 26 years - a prospective secondary analysis of the Stockholm Female Coronary Risk Study.

OBJECTIVE: The prognosis of coronary artery disease (CAD) is related to its severity and cardiovascular risk factors in both sexes. In women, social isolation, marital stress, sedentary lifestyle and depression predicted CAD progression and outcome within 3 to 5 years. We hypothesised that these behavioral factors would still be associated with all-cause mortality in female patients after 26 years. METHODS: We examined 292 patients with CAD and 300 healthy controls (mean age of 56 ± 7 y) within the Fem-Cor-Risk-Study at baseline. Their cardiac, behavioral, and psychosocial risk profiles, exercise, smoking, and dietary habits were assessed using standardized procedures. Physiological characteristics included a full lipid profile, the coagulation cascade and autonomic dysfunction (heart rate variability, HRV). A new exploratory analysis using machine-learning algorithms compared the effects of social and behavioral mechanisms with standard risk factors. Results: All-cause mortality records were completed in 286 (97.9%) patients and 299 (99.7%) healthy women. During a median follow-up of 26 years, 158 (55.2%) patients and 101 (33.9%) matched healthy controls died. The annualized mortality rate was 2.1% and 1.3%, respectively. After controlling for all available confounders, behavioral predictors of survival in patients were social integration (HR 0.99, 95% CI 0.99-1.0) and physical activity (HR 0.54, 95% CI 0.37-0.79). Smoking acted as a predictor of all-cause mortality (HR 1.56, 95% CI 1.03-2.36). Among healthy women, moderate physical activity (HR 0.42, 95% CI 0.24-0.74) and complete HRV recordings (≥50%) were found to be significant predictors of survival. CONCLUSIONS: CAD patients with adequate social integration, who do not smoke and are physically active, have a favorable long-term prognosis. The exact survival times confirm that behavioral risk factors are associated with all-cause mortality in female CAD patients and healthy controls.

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.

The effects of usual Care in Psychosocial Intervention Trials of patients with coronary artery disease: a systematic review.

BACKGROUND: Many intervention studies of coronary artery disease (CAD) have found health benefits for patients in the "treatment as usual" (TAU) group like in the specific psychotherapy group. In this pilot study, we wanted to examine and discuss the role and reasons for TAU effects. METHODS: By means of a systematic review, we examined the control conditions from psychotherapeutic RCTs with CAD patients related to depressive symptoms, mortality and recurrence rate of events. The review question was limited to factors influencing the TAU effectiveness in such psychotherapeutic outcome studies. RESULTS: We found a decrease in depressive symptoms in TAU patients (mean ES: 0.65) and very differing mortality and recurrence rates of events. The effects were dependant on the year the study was published (1986-2016), the follow-up time of the study (0.25-7.8 years) and the treatment arms. A small dose of additional counselling, medical attention, and teaching of therapeutic techniques with clinical competence may reinforce the therapeutic alliance. These factors would be possible moderators of control group efficacy related to the reduction in depressive symptoms and a decrease in mortality and events. CONCLUSION: In the reviewed studies, we found that the control condition was beneficial for CAD patients, but this benefit was highly variable. Specified psychotherapeutic interventions showed an additional independent effect of treatment on depression and effects on morbidity and mortality. There is a need to identify patients at risk of remaining depressed or under severe stress during usual care. These patients may require additional psychosocial intervention.

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.

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.

History, aims and present structure of psychosomatic medicine in Germany.

Combining its two traditions of integrated psychosomatics in internal medicine and focusing on psychotherapeutic/psychiatric methods in many clinical fields, German psychosomatic medicine has developed well over the last decades. It benefits from its institutional independence and the progressive changes in health care. Clinically, disorder-oriented psychotherapy is a core method integrated with other modes of therapy. As a conceptual base for empirical research, non-reductionist accounts of the interactions of (sick) persons with their environment are most important. Germany has developed a model of Psychosomatic Medicine that has conceptualized and integrated psychotherapeutic methods into clinical practice and realized one way to practice bio-psycho-social medicine in the health care system of the country.

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.

[Bio-psycho-socio or psychotherapeutic medicine - actual development of psychosomatics in clinical practice]. / Bio-psycho-soziale oder psychotherapeutische Medizin ­ zur aktuellen Entwicklung der Psychosomatik in der klinischen Praxis.

In Germany a model of Psychosomatic Medicine has developed, which integrated several psychotherapeutic methods in clinical practice. The concept, which focused on disease mechanisms in the human body and the interaction between diseased individuals and their environment became a basic psychosomatic research strategy and was imlemented in medical care. In this paper the result of a psychosomatic development in clinical health care and research and possible deficiences are described. Perspectives of development and future tasks of Psychosomatic Medicine will be reviewed.

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.

The European Network on Psychosomatic Medicine (ENPM) - history and future directions.

BACKGROUND: Within national and international societies of psychosomatic medicine the idea has emerged of bringing together and coordinating psychosomatic, behavioural, psychological and medical actions with common interests throughout Europe as a way to increase their scientific and political influence. METHODS: It was felt that there was a strong need and opportunity of a common and unifying forum for scientific exchange. RESULTS: It was considered desirable to exchange scientific thoughts and experiences in an open minded and boundless way, among individuals and societies, between disciplines and across borders. The course of ideas and discussions within the group of European psychosomatic scientists over 12 years is presented as an effort to combine strengths and actions supporting clinical psychosomatic research and medical practice in Europe. The fields of psycho-cardiology, quality in primary care, psycho-oncology, gastrointestinal psychosomatics, C/L Psychiatry, and Psychosomatics are examples of such positive developments. DISCUSSION: Several historic ideas are mentioned and the aims and advantages of the newly founded European Association of Psychosomatic Medicine are discussed. The advantages and virtues of a more powerful common European organisation of Psychosomatic Medicine and Psychiatric Consultation-Liaison are compared to continuing our work within the present Psychosomatic/Psychiatric and Behavioural fields. CONCLUSION: Psychosomatic and Behavioural Medicine have reached a strong position in Europe. There are studies in which the medical speciality is on equal terms with psychosomatic medicine representatives. There is a continuous need for scientific conferences, for teaching, and for better practice with patients. This could be coordinated by a network. Much energy and time is lost in isolated societies and countries. We want to focus our resources in scientific projects within the boundaries of a scientific network with the primary aim of developing psychosomatic scientific exchange.