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.

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.

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.

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.

Depressive symptoms and heart rate variability in younger women after an acute coronary event.

OBJECTIVES: We investigated associations between depressive symptoms and reduced heart rate variability (HRV) in women aged 30-65 years after an acute coronary event. BACKGROUND: Younger women have an increased mortality after myocardial infarction compared with men of similar age. Depression was hypothesized to contribute to the poor prognosis, possibly mediated by increased susceptibility to arrhythmias. METHODS: The Stockholm Female Coronary Risk study comprised of 292 women aged 30-65 years who were consecutively admitted for myocardial infarction or unstable angina pectoris during a 3-year period. Depressive symptoms were assessed by means of a 9-item questionnaire. Women with no or only one depressive symptom were classified as low-depression individuals, those with two or more depressive symptoms as high-depression individuals. HRV data were calculated from 24-h ambulatory electrocardiographic recordings 3-6 months after the initial event. RESULTS: Reliable HRV data were obtained from 266 patients. Seventy women were low-depression individuals, and 196 women were high-depression individuals. In univariate analyses, the index of standard deviations of R-R intervals, very low-frequency power, low-frequency power and high-frequency power of HRV were lower in the high-depression individuals. After controlling for potential confounders (diabetes, hypertension, systolic blood pressure, body mass index and ß-blocker medication), a significant difference between low and high-depression individuals was maintained for all indices except for high-frequency power. CONCLUSION: The presence of two or more depressive symptoms was associated with reduced HRV in a high-risk group of younger women after an acute coronary event.

Melatonin improves memory acquisition under stress independent of stress hormone release.

RATIONALE: Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. OBJECTIVES: We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans. As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function. MATERIALS AND METHODS: Fifty healthy young men received a single oral dose of either 3 mg melatonin (n = 27) or placebo medication (n = 23). One hour later, they were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). During stress, subjects encoded objects distributed in the test room, for which memory was assessed a day later ("memory encoding under stress"). Fifteen minutes following stress, memory retrieval for words learnt the day before was tested ("memory retrieval after stress"). Plasma epinephrine and norepinephrine levels, salivary free cortisol levels and psychological responses (attention, wakefulness) were repeatedly measured before and after stress exposure. RESULTS: Melatonin specifically enhanced recognition memory accuracy of objects encoded under stress (p < 0.001). In contrast, 15 min after stress, when cortisol levels were highest, retrieval of memories acquired the day before was not influenced by melatonin. Moreover, melatonin did not influence stress-induced elevation of catecholamine and cortisol levels which in turn did not correlate with the effects of melatonin on memory. CONCLUSIONS: The findings point to a primary action of melatonin on central nervous stimulus processing under conditions of stress and possibly on memory consolidation and exclude any substantial suppressive action of the substance on hormonal stress responses.

Cardiovascular reactivity of patients with essential and renal hypertension in an emotion-triggering interview.

Blood pressure reactivity to mental stress in hypertensives is much higher than in normotensives. The authors' aim in this study was to examine whether different cardiovascular responses can be induced by various stimuli in hypertensive subgroups. The authors matched 10 essential hypertensives (EHs), 10 renal hypertensives (RHs), and 10 normotensives (Ns) according to age and gender examined them during an emotion-stimulating interview, and measured blood pressure (BP) and heart rate (HR) during the phases of the interview. They observed differences in BP reactivity between EHs/RHs and Ns under some stimuli but not between EHs and RHs, as well as a marked difference in the product of systolic BP (SBP) and HR between both hypertensive groups in the anger/rage phase (p = .028) and the baseline 2 (p = .02). This shows a higher cardiovascular activation under mental stress and a lower recovery in EHs and more sensitivity to perturbation or higher central tension compared with RHs.

Acute psychological stress alerts the adaptive immune response: stress-induced mobilization of effector T cells.

Influences of psychological stress on the acquired immune system have not consequently been investigated. We found acute psychological stress to cause an increase in CD56+ and CCR5+ effector T cells in the peripheral blood of healthy human subjects (N=22), while skin-homing CLA+ T cells decreased. At the same time, we observed a stress-induced decrease in CD45RA+/CCR7+ naive and CD45RA-/CCR7+ central memory T cells, while CD45RA-/CCR7- effector memory and CD45RA+/CCR7- terminally differentiated T cells increased. This T cell redistribution translated into an increase in T cells expressing perforin/granzyme B and in Epstein-Barr virus-specific, cytomegalovirus-specific and influenza virus-specific CD8+ T cells. Thus, acute stress seems to promote the retention of less mature T cells within lymphoid tissue or skin while effector-type T cells are mobilized into the blood in order to be able to rapidly migrate into peripheral tissues.