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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 ± 9.5 years; 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 [ABSTRACT FROM AUTHOR]

Objectives It has been postulated that patients with heart failure have a high risk of ventricular arrhythmias and sudden cardiac death resulting from anxiety-induced autonomic arousal. In the prospective and multicenter DIAST-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) study, we therefore, tested the hypothesis that adrenomedullin (ADM), a well-established predictor for cardiovascular outcome, is associated with self-rated anxiety symptoms in patients at risk of suffering from or actually with overt heart failure. Participants and measures Study participants with risk factors for diastolic dysfunction were requested to complete the Hospital Anxiety and Depression Scale (HADS), and plasma mid-regional pro-adrenomedullin (MR-proADM) concentrations were measured. Results In bivariate analysis, we found significantly lower plasma MR-proADM levels in patients with elevated HADS-anxiety scores above the clinically relevant cut-off level of ≥11 ( n = 118, 536 pmol/l, interquartile range [IQR] 449–626) as compared to non-anxious study participants ( n = 1,292, 573 pmol/l, IQR 486–702, p = 0.001). A set of multivariate models adjusted for potential confounders confirmed the negative association between self-rated anxiety symptoms and plasma MR-proADM. In similar models, no significant association was detected between HADS-depression scores and MR-proADM. Conclusions The inverse relationship between plasma MR-proADM and anxiety observed in patients with cardiovascular risk factors supports a previous experimental study using a mutant mouse line with a brain-specific loss of ADM expression which displayed hyperactive and over-anxious behavior. Further experimental and clinical studies are warranted to test the hypothesis that also in humans ADM acts as a neuromodulator with anxiolytic properties. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the study was to systematically analyze the stability of Type-D personality over a time span of several years in a clinical sample. Methods: In a prospective cohort study, cardiac patients from different medical settings in Germany were assessed using the DS14 questionnaire at baseline (n=1240) and at a mean follow-up time of six years (n=679). Different types of stability were examined and compared with the stability of the Hospital Anxiety and Depression Scale (HADS). Results: Rank-order stability was moderate (r=.61 for Negative Affectivity [NA] and r=.60 for Social Inhibition [SI]) and didn''t differ from the rank-order stability of the HADS. Whereas the mean level of SI didn''t change over time, the mean level of NA increased (d=0.08). On an individual level, approximately one quarter of the participants showed a significant increase or decrease. The factorial structure of the DS14 was stable over time. Finally, the agreement of Type-D classification between the two measurement points was moderate (κ=.42) with 22% of the participants changing their Type-D classification over time. Conclusion: The stability of NA and SI didn''t differ from the stability of measures of emotional distress that are generally considered to be less stable. In particular, the only moderate stability of the dichotomous Type-D classification raises some questions. [Copyright &y& Elsevier]

Background: Quality of life (QoL) is impaired in diastolic heart failure. Little is known about QoL in diastolic dysfunction (DD) without heart failure. Methods: In the DIAST-CHF observational study, outpatients with risk factors for or a history of heart failure were included. In a cross-sectional analysis, we classified patients with preserved systolic function as having normal diastolic function (N, n = 264) or DD without (DD−, n = 957) or with (DD+, n = 321) elevated filling pressures according to echocardiography. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. Results: Short Form 36 physical function (SF-36-PF) was worse in DD+ (mean ± SD 67.2 ± 25.6) than in DD− (76.2 ± 22.7, P < .05) than in N (mean ± SD 81.1 ± 23.5, P < .01). Other physical dimensions and the physical component score were also lower in DD, whereas the mental component score did not differ. The SF-36-PF correlated weakly with echocardiographic indicators of diastolic function. In multivariate linear regression controlling for age, sex, body mass index, depressiveness as assessed by Patient Health Questionnaire 9, N-terminal probrain-type natriuretic peptide, and midregional proadrenomedullin (MR-proADM), individual echocardiographic parameters or grade of DD was not independently associated with SF-36-PF, whereas the presence of DD+ was. Both N-terminal probrain-type natriuretic peptide and MR-proADM were independently associated with SF-36-PF, with MR-proADM showing the stronger association. Conclusions: Physical dimensions of QoL are reduced in DD. Impaired SF-36-PF is only weakly associated with DD per se but rather seems to be contingent on the presence of elevated filling pressures. Biomarkers are more strongly and independently associated with SF-36-PF and may be more adequate surrogate markers of QoL in DD than echocardiographic measurements. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the independent effects of positive and negative affect items on mortality in consecutive medical inpatients. Methods: Consecutive general medical inpatients were asked to complete the Hospital Anxiety and Depression Scale (HADS) at admission. Prognostic indicators were obtained from patients'' records and physicians'' ratings. The study end point was mortality from all causes at 1 year. Results: The baseline assessment was completed by 575 patients (87.7%). Survival data were available for 572 of these (86 deaths). HADS depression scores and several physical risk indicators predicted mortality. Independent effects could be observed for HADS item 1 (“Can enjoy things as much as before”) adjusted for physicians'' ratings of prognosis, a principal diagnosis of hemato-oncological disease and Charlson comorbidity scores. In contrast, HADS depression items 2–7 (Model 1) as well as positive HADS depression scores did not contribute significantly to the prediction of mortality. Conclusion: Our present results suggest that one single item on positive affect independently predicts 1-year survival in consecutively admitted medical inpatients. Interestingly, this item has a stronger association with survival status than the presence of depressed mood. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to evaluate whether depressive symptoms and the type-D personality are predictive of early recurrence of atrial fibrillation (or atrial flutter; AF) after successful electrical cardioversion (CV). Background: Depressive symptoms are associated with an adverse prognosis in patients with coronary artery disease, congestive heart failure, and ventricular arrhythmias. Anger and hostility have been shown to be predictive of development of AF. However, little is known about the effects of depression on AF. Methods: Fifty-four patients with persistent AF completed the Hospital Anxiety and Depression Scale (HADS) and the Type D Scale (DS-14) prior to elective electrical CV. Patients with a successful CV were followed for 2 months. Results: During the follow-up period, 27 patients (50%) had recurrence of the arrhythmia. Depressive mood (HADS depression scale >7) was the only significant nonsomatic predictor of recurrence, which was observed in 85% of depressed versus 39% of nondepressed patients [odds ratio=8.6; 95% confidence interval (CI)=1.7–44.0, P=.004]. HADS anxiety scores and the presence of the type-D personality pattern were not associated with recurrence of AF. On multivariate Cox regression analysis, including variables with a prevalence >10% of the total study population and a univariate discriminative effect yielding a P value of <.2, a HADS depression score >7 was found to be the only independently predictive variable of arrhythmia recurrence (hazard ratio=2.7; 95% CI=1.05–7.2; P=.046). Conclusions: Our results indicate that depressive mood is a major risk factor for recurrence of AF after electrical CV. Heightened adrenergic tone and a proinflammatory state are possible mechanisms responsible for the observed association. Identification of depression may be of value prior to the decision to perform electrical CV. [Copyright &y& Elsevier]

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Highlights from the article: We correlatied baseline NT-proBNP with Hospital Anxiety and Depression Scale anxiety (HADS-A) scores at baseline and 12 months. Higher NT-proBNP indicates more severe disease but is related to lower anxiety in patients with HFpEF.

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 ± 8.1 to 22.1 ± 11.7 in the intervention group (IG) and from 29.2 ± 8.2 to 25.1 ± 11.3 in the control group (CG). In men VE decreased from 23.3 + -10.8 to 21.2 ± 9.7 in the IG and from 23.6 ± 10.7 to 19.3 ± 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. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the psychometric properties and validity of the updated version of the Dutch multidimensional Comprehensive Psychosocial Screening Instrument in patients with coronary heart disease and the general population, based upon guideline recommendations from the European Society for Cardiology.Method: 678 participants (Mage = 48.2, SD = 16.8; 46% male) of the Dutch general population and 312 cardiac patients (Mage = 65.9, SD = 9.9; 77% male) who recently received percutaneous coronary intervention completed the Comprehensive Psychosocial Screening Instrument and validated questionnaires for depression (PHQ-9), anxiety (GAD-7), Type D personality (DS14), hostility (CMHS), anger (STAS-T), trauma (SRIP), and chronic work and family stress (ERI, MMQ-6).Results: Confirmatory factor analysis (CFA) confirmed that the eight screened risk factors were best measured as separate entities, rather than broader indications of distress. Inter-instrument agreement, assessed with the intraclass coefficient (ICC) and the screening accuracy indicators (receiving operator characteristic [ROC] curves, sensitivity, specificity, and the positive and negative predictive values [PPV; NPV]) were good for most screened risk factors. PPV was low in low prevalence risk factors like anxiety, trauma, and depression.Conclusion: Overall, the current version of the Comprehensive Psychosocial Screening Instrument has an acceptable performance in both populations, with a fair to excellent level of agreement with established full questionnaires. Besides a few suggestions for further refinement, the screener may be implemented in primary care and cardiological practice. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether the use and adjustment of antidepressant pharmacotherapy accounted for the beneficial effects of collaborative care treatment on the improvement of mood symptoms and health-related quality of life (HRQoL) after coronary artery bypass graft (CABG) surgery. Methods: In a post-hoc analysis of data from the Bypassing the Blues (BtB) trial we tested the impact of antidepressant medication on changes in depression and HRQoL from the early postoperative period to 8-month follow-up. Two hundred fifty-nine depressed post-CABG patients scoring ≥10 on the Patient Health Questionnaire-9 were classified in four groups according to whether or not they received antidepressants at baseline and 8-months following randomization. Results: Patients using antidepressant pharmacotherapy at baseline and follow-up tended to be younger and female (p≤0.01), but were similar in various clinical characteristics. Just 24% (63/259) of patients were on an antidepressant at baseline which increased to 36% at follow-up (94/259). Compared to other groups, patients on antidepressants at both baseline and follow-up assessment showed the smallest improvement in mood symptoms and HRQoL. While multivariate analyses confirmed that randomization to collaborative care was associated with greater improvement in mood symptoms (odds ratio [OR]=3.1; 95%-confidence interval [CI]=1.8–5.4, p<0.0001) and mental HRQoL (OR=3.6, CI=1.4–9.3, p=0.01), use of antidepressant medication had no differential impact on either measure (p=0.06 and p=0.92, respectively). Conclusion: The beneficial effects of collaborative care for post-CABG depression were not generated by adjustments in antidepressant medication. Trial Registration: Clinicaltrials.gov Identifier: NCT00091962. (http://clinicaltrials.gov/ct2/show/NCT00091962?term=rollman+cabg&rank=1). [Copyright &y& Elsevier]

Abstract: Objective: Emotionally stressful events appear to trigger malignant ventricular arrhythmias and myocardial infarction in cardiac patients. However, the physiological pathways linking psychological stress to arrhythmias and adverse disease outcomes remain incompletely understood. In patients with implanted cardioverter-defibrillators (ICD) we investigated the impact of emotions and social support on cardiovascular recovery from mental stress. The hypothesis tested was that psychosocial resources help to maintain adaptive hemodynamic responses to mental stress. Methods: In 55 ICD patients we noninvasively measured hemodynamic and autonomic parameters during two sequentially performed mental stress tests (arithmetic and anger recall tests). The cardiovascular data obtained were associated with results from well-validated psychometric self-rating tests for anxiety and depression (HADS), anger (STAXI), and perceived social support (FSozU). Results: In the rest period after mental stress application the majority of the study participants (82%) showed a rapid fall in cardiac index, arterial blood pressure, and heart rate, as well as an increase in high-frequency heart rate variability, while the remainder had no or unexpected changes in the hemodynamic parameters examined. Patients missing hemodynamic recovery in the post-stress phase reported significantly less social support than normally reacting patients (P<.05). Multivariate logistic regression models confirm that social support is an independent and significant predictor of preserved hemodynamic recovery from mental stress, even after controlling for somatic confounders (multivariate odds ratio 4.1; 95% confidence interval 1.3–12.7; P=.015). Conclusions: Our data indicate that in ICD patients better perceived social support is associated with a more pronounced hemodynamic recovery after mental stress. [Copyright &y& Elsevier]

Highlights • In patients with CV risk factors, serum CT-proAVP is associated with anxiety. • The link between CT-proAVP and anxiety is independent of physical impairment. • CT-proAVP is a significant predictor for anxiety, independent of natriuretic peptides. • Fully adjusted models showed an inverse association exclusively in men. • In contrast to male participants, no significant association was observed in women. Abstract Aim Using data from the multicenter, observational Diast-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) study, this post-hoc analysis aimed at assessing the association between serum concentrations of C-terminal pro-arginine vasopressin (CT-proAVP) and anxiety in patients with cardiovascular risk factors. Background Animal studies have demonstrated that centrally released AVP is involved in the development of anxiety-like behaviors, however, it is unknown whether, also in humans, CT-proAVP used as a proxy for the co-secreted AVP is associated with self-reported anxiety. Methods In 1463 study participants with cardiovascular risk factors (mean age 66.7 ± 8.1 years, 51.3% males, mean left ventricular ejection fraction 59.8 ± 8.3%), serum concentrations of CT-proAVP were measured by means of an ELISA assay, and anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). Results Data showed that there was a significant and inverse correlation between HADS anxiety and CT-proAVP (rho = −0.074; p = 0.005). Serum CT-proAVP and the HADS anxiety differed between the two sexes: men displayed lower anxiety (4.7 ± 3.5 versus 5.5 ± 3.7) and had higher CT-proAVP levels (5.8 pmol/L, interquartile range 3.5–9.9 pmol/L versus 3.0 pmol/L, interquartile range 2.0–4.7) than women (both, p < 0.001). Using univariate ANOVA adjusted for age, body-mass index, estimated glomerular filtration rate, left ventricular ejection fraction, 6-minute walking distance, SF-36 physical functioning, and the natriuretic peptides NT-proBNP and MR-proANP, the interaction term sex*CT-proAVP was significantly associated with anxiety (p = 0.006). Further analysis showed that CT-proAVP was inversely related to anxiety only in men (B = −0.991; 95%CI = −1.650 to −0.331; p = 0.003), but not in women (p = 0.335). Conclusion In male study participants with cardiovascular risk factors, serum concentrations of CT-proAVP showed an inverse association with anxiety, which was independent from the severity of physical impairment. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is associated with impaired health-related quality of life (HRQoL), an increased risk of morbidity, and mortality. Traditional AF-related outcomes (e.g., AF recurrence) primarily demonstrate the physiological benefits of AF management but do not focus on the benefits experienced subjectively by the patient (i.e., patient-reported outcomes), which have been suggested as optimal endpoints in AF intervention studies. The aim of this study is to identify medical and psychological factors associated with impaired HRQoL at 1-year follow-up. Using data from the prospective observational multicenter ARENA study in patients with AF, we analyzed associations between medical factors, anxiety, and HRQoL at 1-year follow-up assessed using 5-level EuroQoL-5D. In 1353 AF patients (mean age 71.4 ± 10.3 years, 33.8% female), none of the medical predictors (e.g., heart disease) or history of cardioversion were associated with HRQoL at the 1-year follow-up. Higher generalized anxiety (β = -0.114, p <.001) but not cardiac anxiety (β = -0.006, p =.809) at baseline predicted decreased HRQoL, independent of confounding variables and patients' medical status. Furthermore, the worsening of patients' generalized anxiety was associated with decreased HRQoL (ß = -0.091, p <.001). In contrast, the improvement of generalized anxiety over time predicted higher HRQoL (ß = 0.097, p <.001). Finally, the worsening of patients' cardiac anxiety over time was associated with decreased HRQoL (ß = -0.081, p <.001). Our results highlight the importance of anxiety as a predictor of future HRQoL in patients with AF. Additional studies to examine the impact of anxiety treatment on HRQoL in this population are needed. The investigators registered on ClinicalTrials.gov (NCT02978248) on November 30, 2016 https://clinicaltrials.gov/ct2/show/NCT02978248. • Screening of anxiety might identify AF patients at elevated risk for impaired HRQoL. • Anxiety is a robust and independent predictor of future HRQoL in individuals with AF. • None of the medical predictors were associated with HRQoL at 1-year FU in AF patients. • Treatment of anxiety symptoms might lead to improvements of HRQoL in AF patients. [ABSTRACT FROM AUTHOR]

Highlights • In depressed CAD patients, serum NT-proBNP is associated with better mental health. • Patients with higher levels of serum NT-proBNP experience less bodily pain. • BNP peptide may have a protective function against psychosocial distress. Abstract 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with heart failure often experience impaired health-related quality of life (HRQOL) and have an increased risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the predictive role of different coping styles on outcome. This longitudinal study included 1536 participants who either had cardiovascular risk factors or were diagnosed with heart failure. Follow-ups took place one, two, five and ten years after recruitment. Coping and HRQOL were investigated using self-assessment questionnaires (Freiburg Questionnaire for Coping with Illness, Short Form-36 Health Survey). Somatic outcome was quantified by incidence of major adverse cardiac and cerebrovascular events (MACCE) and 6-min-walking-distance. Pearson correlation and multiple linear regression analysis showed significant associations between the coping styles used at the first three time points and HRQOL after five years. After adjusting for baseline HRQOL, minimization and wishful thinking predicted worse mental HRQOL (β = −0.106; p = 0.006), while depressive coping predicted worse mental (β = −0.197; p < 0.001) and physical HRQOL (β = −0.085; p = 0.03; n = 613). Active problem-oriented coping could not significantly predict HRQOL. Only minimization and wishful thinking was significantly associated with an increased 10-year-risk for MACCE (hazard ratio = 1.06; 95% confidence interval: 1.01–1.11; p = 0.02; n = 1444) and reduction in 6-min-walking-distance at 5 years (β = −0.119; p = 0.004; n = 817) in adjusted analyses. Depressive coping and minimization and wishful thinking were associated with worse quality of life in patients at risk for or with diagnosed heart failure. Minimization and wishful thinking also predicted worse somatic outcome. Therefore, patients using those coping styles might benefit from early psychosocial interventions. • Coping strategies predict outcome of patients at risk for or with heart failure. • Depressive coping predicts worse quality of life. • Minimization & wishful thinking predicts worse somatic outcome and quality of life. [ABSTRACT FROM AUTHOR]

Defective cooperative DNA binding of STAT1 (signal transducer and activator of transcription 1) transcription factor has impact on interferon-γ(IFNγ)-regulated transcriptional responses. In this study, we generated N-terminal gain-of-function mutants of this protein which exhibited hyperactive cooperativity and assessed their functional consequences on gene expression. Our data show that four negatively charged, surface-exposed amino acid residues in the N-terminal domain dimer are engaged in the disassembly of tyrosine-phosphorylated tetrameric complexes on DNA and prevent the occurrence of higher-order STAT1 oligomers on low-affinity DNA binding sites. Owing to their improved tetramer stability, the N-terminal mutants showed relaxed sequence requirements for the binding to DNA as compared to the wild-type protein. Similarly to a STAT1 mutant with impaired tetramerization, the N-terminal gain-of-function mutants showed elevated tyrosine-phosphorylation levels and prolonged nuclear accumulation upon stimulation of cells with IFNγ. However, in contrast to the global impairment of IFNγ signalling in tetramerization-deficient mutants, the transcriptional consequences of the N-terminal gain-of-function mutants are rather distinct and affect gene expression locally in a promoter-specific manner. Thus, we conclude that the STAT1 N-domain acts as a double-edged sword: while one interface is crucial for the formation of tetrameric complexes on IFNγ-regulated promoters, the opposite interface harbours an inhibitory mechanism that limits the accumulation of higher-order oligomers simply by disrupting cooperative DNA binding. [ABSTRACT FROM AUTHOR]

Abstract: Background: To investigate the interaction of clinical characteristics with disease characterising parameters in heart failure with preserved ejection fraction (HFpEF). Methods and results In the multicenter, randomized, placebo-controlled, double-blinded, Aldo-DHF trial investigating the effects of spironolactone on exercise capacity (peakVO2) and diastolic function (E/e′) n =422 patients with HFpEF (age 67±8years, 52% females, LVEF 67±8%) were included. After multiple adjustment, higher age was significantly related to reduced peakVO2, and to increased E/e′, NT-proBNP, LAVI as well as LVMI (all p <0.05). Female gender (p <0.001), CAD (p =0.002), BMI (p <0.001), sleep apnoea (p =0.02), and chronotropic incompetence (CI, p =0.002) were related to lower peakVO2 values. Higher pulse pressure (p =0.04), lower heart rates (p =0.03), CI (p =0.03) and beta-blocker treatment (p =0.001) were associated with higher E/e′. BMI correlated inversely (p =0.03), whereas atrial fibrillation (p <0.001), lower haemoglobin levels (p <0.001), CI (p =0.02), and beta-blocker treatment (p <0.001) were associated with higher NT-proBNP. After multiple adjustment for demographic and clinical variables peakVO2 was not significantly associated with E/e′ (r =+0.01, p =0.87), logNT-proBNP (r =0.09, p =0.08), LAVI (r =+0.03, p =0.55), and LVMI (r =+0.05, p =0.37). The associations of E/e′ with logNT-proBNP (r =0.21, p <0.001), LAVI (r =+0.29, p <0.001) and LVMI (r =0.09, p =0.06) were detectable also after multiple adjustment. Conclusions: Demographic and clinical characteristics differentially interact with exercise capacity, resting left ventricular filling index, neurohumoral activation, and left atrial and ventricular remodelling in HFpEF. Exercise intolerance in HFpEF is multi-factorial and therapeutic approaches addressing exercise capacity should therefore not only aim to improve single pathological mechanisms. Registration: ISRCTN94726526 (http://www.controlled-trials.com), Eudra-CT-number 2006-002605-31. [Copyright &y& Elsevier]

Abstract: Background: Self-rated health (SRH) predicts outcome in patients with heart failure. Beta-blockers are known to improve health-related quality of life and reduce mortality in such patients. We aimed to evaluate the relation between SRH and adverse events during titration of beta-blockers in elderly patients with heart failure. Methods: The cardiac insufficiency bisoprolol study in the elderly (CIBIS-ELD) is a multicentre, double-blind trial, in which 883 patients aged ≥65years with chronic heart failure (73±6years, 38% women, left ventricular ejection fraction [LVEF] 42%±14%) were randomised to bisoprolol or carvedilol. SRH was assessed at baseline and after 12weeks, using a 5-grade descriptive scale: excellent, very good, good, fair, and poor. Results: Median SRH at baseline and follow-up was good, but more patients reported fair/poor SRH at baseline (36% vs. 30%, p=0.012). Women, beta-blocker-naïve patients, patients in NYHA class III/IV and those with PHQ-9 score ≥12 were more likely to report fair/poor baseline SRH (p<0.001 for all). During follow-up, SRH improved in 34% of patients and worsened in 8% (p<0.001). Adverse events were experienced by 64% patients and 38% experienced >1 adverse event or serious adverse event, with higher prevalence in lower SRH categories. In a multivariate logistic regression model, SRH, age, distance achieved on the 6-min walk test and LVEF >45% predicted adverse events (p<0.05 for all). Conclusions: SRH is an independent predictor of adverse events during titration of beta-blockers and correlates with the proportion and number of adverse events per patient. [Copyright &y& Elsevier]

Abstract: Background: It has been suggested that patients with chronic HF and atrial fibrillation (AF) may respond differently to beta-blockers than those in sinus rhythm (SR). Methods: In this predefined analysis of the CIBIS-ELD trial, a total of 876 chronic HF patients (164 patients with AF) were randomized to bisoprolol or carvedilol. During the 12-week-treatment phase, beta-blockers were doubled fortnightly up to the target dose or maximally tolerated dose, which was maintained for 4weeks. Results: Patients with AF had lower left ventricular ejection fraction (LVEF), exercise capacity, self-rated health, quality of life (QoL) scores for both SF36 physical and psychosocial component, and higher NYHA class than those in SR. Beta-blocker titration was associated with clinical improvement in both AF and SR patients: LVEF, 6-minute walk distance, physical and psychosocial components of QoL scores, self-rated health and NYHA class (p<0.05, for all). The extent of improvement did not differ between patients with AF and in SR and did not differ between bisoprolol and carvedilol. Heart rate (HR) at baseline was higher in the AF group, and remained higher until the end of the trial. Patients with higher baseline HR had larger reductions in HR, regardless of rhythm. AF patients more frequently reached target beta-blocker dose compared to those in SR (p<0.005). Conclusions: Elderly patients with chronic HF and AF derive comparable clinical benefits from beta-blocker titration as those in SR. Patients with AF tolerate higher beta-blocker doses than those in SR, which appears to be related to higher baseline HR. [Copyright &y& Elsevier]

Objectives: We sought to determine whether structured exercise training (ET) improves maximal exercise capacity, left ventricular diastolic function, and quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF). Background: Nearly one-half of patients with heart failure experience HFpEF, but effective therapeutic strategies are sparse. Methods: A total of 64 patients (age 65 ± 7 years, 56% female) with HFpEF were prospectively randomized (2:1) to supervised endurance/resistance training in addition to usual care (ET, n = 44) or to usual care alone (UC) (n = 20). The primary endpoint was the change in peak Vo 2 after 3 months. Secondary endpoints included effects on cardiac structure, diastolic function, and QoL. Results: Peak Vo 2 increased (16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg; p < 0.001) with ET and remained unchanged (16.7 ± 4.7 ml/min/kg to 16.0 ± 6.0 ml/min/kg; p = NS) with UC. The mean benefit of ET was 3.3 ml/min/kg (95% confidence interval [CI]: 1.8 to 4.8, p < 0.001). E/e′ (mean difference of changes: −3.2, 95% CI: −4.3 to −2.1, p < 0.001) and left atrial volume index (milliliters per square meter) decreased with ET and remained unchanged with UC (−4.0, 95% CI: −5.9 to −2.2, p < 0.001). The physical functioning score (36-Item Short-Form Health Survey) improved with ET and remained unchanged with UC (15, 95% CI: 7 to 24, p < 0.001). The ET-induced decrease of E/e′ was associated with 38% gain in peak Vo 2 and 50% of the improvement in physical functioning score. Conclusions: Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure–Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037) [Copyright &y& Elsevier]

Abstract: Objective: Depressive symptoms are highly relevant for the quality of life, health behavior, and prognosis in patients with coronary artery disease (CAD). However, previous psychotherapy trials in depressed CAD patients produced small to moderate effects on depression, and null effects on cardiac events. In this multicentre psychotherapy trial, symptoms of depression are treated together with the Type D pattern (negative affectivity and social inhibition) in a stepwise approach. Methods: Men and women (N=569, age 18–75years) with any manifestation of CAD and depression scores ≥8 on the Hospital Anxiety and Depression Scale (HADS), will be randomized (allocation ratio 1:1) into the intervention or control group. Patients with severe heart failure, acutely life-threatening conditions, chronic inflammatory disease, severe depressive episodes or other severe mental illness are excluded. Both groups receive usual medical care. Patients in the intervention group receive three initial sessions of supportive individual psychotherapy. After re-evaluation of depression (weeks 4–8), patients with persisting symptoms receive an additional 25 sessions of combined psychodynamic and cognitive–behavioral group therapy. The control group receives one psychosocial counseling session. Primary efficacy variable is the change of depressive symptoms (HADS) from baseline to 18months. Secondary endpoints include cardiac events, remission of depressive disorder (SCID) and Type D pattern, health-related quality of life, cardiovascular risk profile, neuroendocrine and immunological activation, heart rate variability, and health care utilization, up to 24months of follow-up (ISRCTN: 76240576; NCT00705965). Funded by the German Research Foundation. [Copyright &y& Elsevier]

Abstract: The DS14 () is the most accepted and widely used diagnostic instrument for the assessment of the type-D pattern, which has been established as a predictor of adverse clinical events and cardiac prognosis in patients with heart disease. Despite an increasing number of applications of the DS14 in non-cardiac and healthy samples, psychometric properties of the DS14 item and subscale scores have not been tested explicitly for non-cardiac samples, and population-based norms have been missing until now. The present study aimed to analyse the psychometric properties of the item and subscale scores and the factorial structure of the DS14, as well as to examine prevalence rates and to provide population-based norms for the German general population from a population-based representative sample of 2495 subjects. The analyses document sound psychometric properties. A confirmatory factor analysis demonstrated the best fit for a two-factor structure. The prevalence of the type-D personality in the German population was 31%. In comparison, most studies report lower prevalence rates in cardiac patients. The present findings support the use of the DS14 to assess the traits of negative affectivity and social inhibition and to classify type-D personality in epidemiologic research and individual diagnostics as well. [Copyright &y& Elsevier]

Abstract: Objective: The implantable cardioverter defibrillator (ICD) has been proven to prolong the lives of patients with life-threatening ventricular arrhythmia. However, implant recipients must cope with numerous challenges. We studied the effects of specific coping strategies and the adaptability of coping in ICD implant recipients. Method: This prospective study investigated the subjective well-being and objective disease course in 180 patients with life-threatening cardiac arrhythmias, who were recruited while awaiting implantation of a cardioverter defibrillator. Patients completed well-validated self-assessment questionnaires before implantation (T0), as well as 3 months (T1) and 1 year (T2) after implantation. In addition, cardiological findings were documented. Results: Depressive coping (range Beta, −0.36 to −0.58) was found to be a stable highly-significant predictor for low emotional well-being and quality of life. Active problem-oriented coping showed small positive influence (range Beta, 0.10 to 0.19). Employing a broad range of coping strategies was predictive of less emotional distress and better quality of life. Conclusions: Depressive coping is a risk factor for emotional distress and poor quality of life after ICD implantation. Patients with this tendency should be identified early and offered supportive psychotherapy. [Copyright &y& Elsevier]

Abstract: Exaggerated procoagulant responses to acute mental stress may contribute to coronary thrombosis, and continuing low-grade systemic coagulation activation may link negative affect with the development of coronary artery disease. We investigated whether negative and positive affect and perceived social support would moderate stress procoagulant reactivity. Psychological functioning, exhaustion, negative affectivity, depression, anxiety, worrying, vigor, and social support were assessed in 27 apparently healthy men (mean age 47±8 years) who underwent the 13-min Trier Social Stress Test combining preparation, speech, and mental arithmetic. Plasma levels of von Willebrand factor antigen (VWF:Ag), fibrinogen, factor VII clotting activity (FVII:C), FVIII:C, FXII:C, and D-dimer were measured immediately before and after stress. Acute stress elicited significant increases in hemodynamic, cortisol, and coagulant activity (p values&#60;0.05). VWF:Ag reactivity showed inverse relationships with exhaustion (r =−0.63, p &#60;0.001), negative affectivity (r =−0.53, p =0.005), and worrying (r =−0.53, p =0.005). Exhaustion and negative affectivity emerged as independent predictors of VWF:Ag reactivity explaining 54% of its variance. Fibrinogen reactivity showed inverse relationships with negative affectivity (r =−0.59, p =0.002) and anxiety (r =−0.54, p =0.005); negative affectivity emerged as an independent predictor of fibrinogen reactivity explaining 35% of its variance. Psychological functioning and FVII:C reactivity were also correlated (r =−0.52, p =0.006). Whereas FVIII:C reactivity correlated positively with vigorous mood (r =0.48, p =0.012), positive associations between social support and procoagulant reactivity did not reach significance. Negative affect was associated with attenuated procoagulant reactivity to stress and the opposite was observed for positive affect. Negative affect is not likely to enhance the acute procoagulant stress response in healthy men. [Copyright &y& Elsevier]

: ObjectiveTo compare the validity of detecting panic disorder using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), a screening question, and physicians'' diagnosis, and to test whether modified evaluation algorithms improve the operating characteristics of these questionnaires. Additionally, patient and physician acceptability of the screening questionnaires was investigated.: MethodsThe total sample of 499 patients comprised 348 medical outpatients and 151 psychosomatic outpatients. The Structured Clinical Interview for DSM-IV (SCID) was the criterion standard for the presence of a panic disorder. Sensitivity, specificity, predictive values, and overall accuracy were compared for the different measures. The conditional test characteristics were calculated based on the observed prevalence of panic disorder in the medical and psychosomatic subsample, respectively.: ResultsPanic disorder was diagnosed in 4.3% of the medical outpatients and in 19.2% of the psychosomatic outpatients. The HADS, PHQ, and screening question achieved good operating characteristics. In contrast, physicians detected only 15% of cases with panic disorder. Modified evaluation algorithms of the questionnaires lead to an improvement of test characteristics. Of all measures, the PHQ had the best operating characteristics. The use of screening questionnaires was accepted by 96% of the patients and 97% of the physicians.: ConclusionThe questionnaires as well as the screening question performed well in detecting panic disorder. Thus, the integration of these highly accepted measures into clinical evaluation is suggested. Recommendations for the selection of specific evaluation algorithms are given. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background: Stroke can negatively impact the health-related quality of life (HRQoL). Anxiety or depression after stroke have been associated with poorer HRQoL, higher mortality and greater dependence in activities of daily living. We aimed to analyze HRQoL, anxiety and depressive symptoms in patients with and without atrial fibrillation (AF) up to 12 months post-stroke.Methods: Find-AFRANDOMISED was a prospective, randomized multicenter study, which included 398 patients ≥60 years with acute cerebral ischemia. HRQoL data were collected using the 3-level EuroQol-5D (EQ-5D-3L) and Stroke Impact Scale (SIS-16). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). The severity of stroke was measured using the modified Rankin Scale (mRS).Results: In this study (mean age 72.7 ± 7.5 years, 40.2% females), there was a significant improvement in HRQoL using EQ-5D-3L after 3 months (β = 0.37, p < .01), 6 months (β = 0.43, p < .01) and 12 months (β = 0.44, p < .01) post-stroke compared to baseline. HADS anxiety scores after 3 months (β = -0.22, p < .01) and 12 months (β = -0.28, p < .01) were significantly reduced. Older patients reported reduced HRQoL and more depressive symptoms. Females indicated lower HRQoL and more anxiety. mRS score at baseline was an independent predictor for HRQoL. There was a significant but small effect of AF on EQ-5D-3L and on HADS anxiety.Conclusions: Patients showed significant improvement in HRQoL and reduced anxiety after 3 and 12 months after stroke. We could demonstrate that the severity of stroke as well as sex and age impact long-term post-stroke HRQoL.Clinical Trial Registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01855035. [ABSTRACT FROM AUTHOR]

Objective: To examine the role of emotion regulation and its relationship to mental and physical health in patients with heart failure (HF).Methods: Patients hospitalized with HF were screened for depressive symptoms with the two-item Patient Health Questionnaire (PHQ-2) and classified as screen-positive if endorsing ≥1 item and otherwise as screen-negative. One month after hospital discharge, the Emotion Regulation Questionnaire (ERQ) was administered to assess suppression and reappraisal as emotion regulation strategies. In all participants who completed the ERQ (N = 394), all-cause rehospitalization and depressive symptoms using the PHQ-9 were assessed at 1-, 3-, and 6-months after hospital discharge.Results: Overall, PHQ-9 scores decreased by 6-months (-0.13 points/month, p = .003), and although suppression showed a small association with depression, neither strategy modulated the slope of the decline in depressive symptoms. Multivariable-adjusted Cox models showed that reappraisal and suppression were not related to all-cause rehospitalization in the entire cohort. However, increasing reappraisal reduced rehospitalization risk by 24% for screen-positive patients (N = 311, HR = 0.76, p = .02), but increased it by 94% in screen-negative patients (N = 83, HR = 1.94, p = .009).Conclusion: Suppression and reappraisal showed specific and divergent associations in patients with HF: Suppression may relate to depressive symptoms. Reappraisal was associated with rehospitalization, but differently for patients with a positive vs. negative depression screen. Further studies are needed to examine whether emotion-regulation skill training can improve mental and physical health in depressed patients with HF or ameliorate depression in those at-risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Highlights from the article: Health promotion in usual care - Lessons to be learnt from randomized controlled trial's in coronary heart disease (CAD) Many interventions have demonstrated a benefit and health promoting effect in the "usual care (UC)" group. The mortality and recurrence rate of events depends on the year the study was published (1986-2016) and the follow up time of the study (0.25-7.8 years).