Effects of Stress and Psychological Trauma on the Development and Progression of Cardiovascular Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 39828

Special Issue Editors


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Guest Editor
Nueremberg Paracelsus Medical Private University, Nuremberg, Germany
Interests: oxytocin; coronary artery disease; atherosclerosis; early life stress; attachment disorders, posttraumatic stress disorder, allostatic load

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Co-Guest Editor
Anaesthesiology and Intensive Care Medicine, Ulm University, Ulm, Germany
Interests: trauma-and-hemorrhage; traumatic brain injury; septic shock
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Special Issue Information

Dear Colleagues,

As many of you already know, it is well-established that stress and psychological trauma increase the risk of development of cardiovascular diseases, such as hypertension, coronary artery disease, stress cardiomyopathy, and the so-called ‘metabolic syndrome’.

Psychological stress and the subsequent development of mental disorders are becoming increasingly important to our society. However, the pathophysiology and/or mediator systems that link stress and/or psychological trauma to the development of cardiovascular disease remain only partly understood. Over the past few years, a number of multi-center studies and epidemiological data on the topic have emerged, demonstrating that the amount and accumulation of allostatic load and the activation of the hypothalamic–pituitary and/or catecholaminergic axes are important issues. Other (patho)-physiological pathways and biological mediator systems have been identified that also represent major areas of current research activity. This is reflected, for example, by the recent EU ERC Consolidator Grant “Major Depression as a Metabolic Disorder: The Role of Oxygen Homeostasis and Mitochondrial Bioenergetics in Depression Etiology and Therapy”.

Nevertheless, much remains to be learned about the biological mediators that relate psychological stress and or trauma to the pathophysiology of cardiovascular diseases. With this Special Issue, we hope to encourage submissions that discuss the state-of-the-art, fill existing knowledge gaps, and focus on ongoing controversies related to the interaction of stress and psychological trauma with the development and progression of cardiovascular diseases.

Prof. Dr. Christiane Waller
Prof. Dr. Peter Radermacher
Guest Editors

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Keywords

  • post-traumatic stress disorder
  • psycho-neurological inflammatory response
  • allostatic load
  • oxidative and nitrosative stress
  • autonomic nervous system imbalance
  • psycho-neurological endocrine response
  • stress cardiomyopathy
  • stress- and psychological-trauma-related coronary artery syndrome
  • stress resilience factors and cardiovascular homoeostasis.

Published Papers (17 papers)

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14 pages, 1422 KiB  
Article
Heart-Focused Anxiety, General Anxiety, Depression and Health-Related Quality of Life in Patients with Atrial Fibrillation Undergoing Pulmonary Vein Isolation
by Valérie Pavlicek, Sonja Maria Wedegärtner, Dominic Millenaar, Jan Wintrich, Michael Böhm, Ingrid Kindermann and Christian Ukena
J. Clin. Med. 2022, 11(7), 1751; https://doi.org/10.3390/jcm11071751 - 22 Mar 2022
Cited by 6 | Viewed by 1807
Abstract
(1) Background: Atrial fibrillation (AF) is associated with anxiety, depression, and chronic stress, and vice versa. The purpose of this study was to evaluate potential effects of pulmonary vein isolation (PVI) on psychological factors. (2) Methods: Psychological assessment was performed before PVI as [...] Read more.
(1) Background: Atrial fibrillation (AF) is associated with anxiety, depression, and chronic stress, and vice versa. The purpose of this study was to evaluate potential effects of pulmonary vein isolation (PVI) on psychological factors. (2) Methods: Psychological assessment was performed before PVI as well as after six months. (3) Results: A total of 118 patients [age 64 ± 9 years, 69% male, left ventricular ejection fraction 57 ± 8%, 56% paroxysmal AF] undergoing PVI were included. After PVI, significant improvements were observed in the mean total heart-focused anxiety (HFA) score, as well as in the Cardiac Anxiety Questionnaire (CAQ) sub-scores: HFA attention, HFA fear, and HFA avoidance scores. Subgroup analyses showed an association of improvement with freedom of documented AF recurrence. Mean scores of general anxiety and depression evaluated by the Hospital Anxiety and Depression Scale (HADS) decreased significantly after PVI in all subgroups regardless of AF recurrence. Further, both physical and mental composite scores of the Short Form Health Survey (SF-12) increased significantly from baseline. (4) Conclusions: PVI results in a significant reduction in HFA. Improvements in general anxiety and depressive symptoms did not seem to be related only to rhythm control per se. Therefore, CAQ may represent a more specific evaluation tool as HADS in patients with AF. Full article
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10 pages, 948 KiB  
Article
Cortisol Awakening Reaction and Anxiety in Depressed Coronary Artery Disease Patients
by Cora Weber, Stella V. Fangauf, Matthias Michal, Joram Ronel, Christoph Herrmann-Lingen, Karl-Heinz Ladwig, Manfred Beutel, Christian Albus, Wolfgang Söllner, Frank Holger Perschel, Martina de Zwaan, Kurt Fritzsche and Hans-Christian Deter
J. Clin. Med. 2022, 11(2), 374; https://doi.org/10.3390/jcm11020374 - 13 Jan 2022
Cited by 6 | Viewed by 2519
Abstract
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 [...] Read more.
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. Full article
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19 pages, 883 KiB  
Article
The Acute Effects of Aerobic Exercise on Nocturnal and Pre-Sleep Arousal in Patients with Unipolar Depression: Preplanned Secondary Analysis of a Randomized Controlled Trial
by Gavin Brupbacher, Thea Zander-Schellenberg, Doris Straus, Hildburg Porschke, Denis Infanger, Markus Gerber, Roland von Känel and Arno Schmidt-Trucksäss
J. Clin. Med. 2021, 10(17), 4028; https://doi.org/10.3390/jcm10174028 - 6 Sep 2021
Cited by 3 | Viewed by 3308
Abstract
Unipolar depression is associated with insomnia and autonomic arousal. The aim of this study was to quantify the effect of a single bout of aerobic exercise on nocturnal heart rate variability and pre-sleep arousal in patients with depression. This study was designed as [...] Read more.
Unipolar depression is associated with insomnia and autonomic arousal. The aim of this study was to quantify the effect of a single bout of aerobic exercise on nocturnal heart rate variability and pre-sleep arousal in patients with depression. This study was designed as a two-arm, parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients with a primary diagnosis of unipolar depression aged 18–65 years were included. The intervention consisted of a single 30 min moderate-intensity aerobic exercise bout. The control group sat and read for 30 min. The primary outcome of interest was RMSSD during the sleep period assessed with polysomnography. Secondary outcomes were additional heart rate variability outcomes during the sleep and pre-sleep period as well as subjective pre-sleep arousal. A total of 92 patients were randomized to either the exercise (N = 46) or the control (N = 46) group. Intent-to-treat analysis ANCOVA of follow-up sleep period RMSSD, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = 0.12, p = 0.94). There was no evidence for significant differences between both groups in any other heart rate variability measure nor in measures of cognitive or somatic pre-sleep arousal. As this is the first trial of its kind in this population, the findings need to be confirmed in further studies. Patients with depression should be encouraged to exercise regularly in order to profit from the known benefits on sleep and depressive symptoms, which are supported by extensive literature. Full article
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15 pages, 765 KiB  
Article
The Interplay between Child Maltreatment and Stressful Life Events during Adulthood and Cardiovascular Problems—A Representative Study
by Vera Clemens, David Bürgin, Markus Huber-Lang, Paul L. Plener, Elmar Brähler and Jörg M. Fegert
J. Clin. Med. 2021, 10(17), 3937; https://doi.org/10.3390/jcm10173937 - 31 Aug 2021
Cited by 11 | Viewed by 2248
Abstract
Psychological stress is a major risk factor for cardiovascular diseases. While the relevance of early life stress, such as that which is due to child maltreatment (CM), is well known to impact individual stress responses in the long-term, and data on the interplay [...] Read more.
Psychological stress is a major risk factor for cardiovascular diseases. While the relevance of early life stress, such as that which is due to child maltreatment (CM), is well known to impact individual stress responses in the long-term, and data on the interplay between CM and stressful events in adulthood on cardiovascular health are sparse. Here, we aimed to assess how stressful life events in adulthood are associated with cardiovascular health infarction in later life and whether this association is independent of CM. In a cross-sectional design, a probability sample of the German population above the age of 14 was drawn using different sampling steps. The final sample included 2510 persons (53.3% women, mean age: 48.4 years). Participants were asked about sociodemographic factors, adult life events, CM, and health conditions in adulthood. Results indicate that the number of experienced adverse life events in adulthood is associated with significantly increased odds for obesity (Odds Ration (OR)women = 1.6 [1.3; 2.0], ORmen = 1.4 [1.1; 1.9]), diabetes (ORwomen = 1.5 [1.1; 2.1], ORmen = 1.5 [1.1; 2.3]) and myocardial infarction (ORwomen = 2.1 [1.0; 4.3], ORmen = 1.8 [1.1; 2.8]). This association is not moderated by the experience of CM, which is associated with cardiovascular problems independently. Taken together, adult stressful life events and CM are significantly and independently associated with cardiovascular health in men and women in the German population in a dose-dependent manner. General practitioners, cardiologists and health policy-makers should be aware of this association between psychosocial stressors during childhood and adulthood and cardiovascular health. Full article
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7 pages, 225 KiB  
Article
Prevalence and Prognostic Value of Psychological Stress Events in Patients with First Myocardial Infarction—Long-Term Follow-Up Study
by Andrea Jaensch, Ben Schöttker, Roman Schmucker, Wolfgang Koenig, Hermann Brenner and Dietrich Rothenbacher
J. Clin. Med. 2021, 10(16), 3562; https://doi.org/10.3390/jcm10163562 - 13 Aug 2021
Cited by 1 | Viewed by 1442
Abstract
While there is good evidence that symptoms of depression determine prognosis of patients with coronary heart disease (CHD), the role of psychological stress is less clear. We evaluated the prognostic value of stressful events in patients with initial myocardial infarction (MI) with respect [...] Read more.
While there is good evidence that symptoms of depression determine prognosis of patients with coronary heart disease (CHD), the role of psychological stress is less clear. We evaluated the prognostic value of stressful events in patients with initial myocardial infarction (MI) with respect to subsequent cardiovascular events. The KAROLA-study included patients with CHD who participated in an in-patient rehabilitation program. A total of 577 patients with initial MI were included and self-reported psychological stressful events before their MI was assessed by a structured questionnaire. Hazard ratios were used to evaluate the long-term association of stressful events with secondary cardiovascular events. Additionally, associations of stressful events with depression, anxiety and other cardiovascular risk factors were investigated. Unusual stress at work (26.5%) and sleep disorder (23.4%) were the most frequently reported stressful events that occurred in the last 4 weeks before MI. However, only death of a family member showed a statistically significant increase in risk for subsequent cardiovascular events (HR: 1.59; 95%-CI: 1.01–2.50) and this result was not corrected for multiple testing. Notably, we found higher symptom scores of anxiety and depression associated with all single stressful event items. In conclusion, we found no clear patterns that psychological stressful events before MI would increase the long-term risk of subsequent adverse CHD events directly. However, we saw increased symptom scores of anxiety and depression in persons with stressful events. Full article
17 pages, 1044 KiB  
Article
Acute Stress-Induced Blood Lipid Reactivity in Hypertensive and Normotensive Men and Prospective Associations with Future Cardiovascular Risk
by Cathy Degroote, Roland von Känel, Livia Thomas, Claudia Zuccarella-Hackl, Jens C. Pruessner, Roland Wiest and Petra H. Wirtz
J. Clin. Med. 2021, 10(15), 3400; https://doi.org/10.3390/jcm10153400 - 30 Jul 2021
Cited by 5 | Viewed by 2027
Abstract
Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for [...] Read more.
Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension. Full article
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23 pages, 13258 KiB  
Article
5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
by Sandy Popp, Angelika Schmitt-Böhrer, Simon Langer, Ulrich Hofmann, Leif Hommers, Kai Schuh, Stefan Frantz, Klaus-Peter Lesch and Anna Frey
J. Clin. Med. 2021, 10(14), 3104; https://doi.org/10.3390/jcm10143104 - 14 Jul 2021
Cited by 5 | Viewed by 2207
Abstract
Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation [...] Read more.
Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice. Full article
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17 pages, 783 KiB  
Article
Chronic Inflammation Mediates the Association between Cortisol and Hyperglycemia: Findings from the Cross-Sectional Population-Based KORA Age Study
by Hamimatunnisa Johar, Derek Spieler, Martin Bidlingmaier, Christian Herder, Wolfgang Rathmann, Wolfgang Koenig, Annette Peters, Johannes Kruse and Karl-Heinz Ladwig
J. Clin. Med. 2021, 10(13), 2751; https://doi.org/10.3390/jcm10132751 - 22 Jun 2021
Cited by 5 | Viewed by 2071
Abstract
(1) Background: The study aimed to investigate the role of subclinical inflammation on the association between diurnal cortisol patterns and glycaemia in an aged population. (2) Methods: Salivary cortisol, interleukin-6 (IL-6) and glycated haemoglobin (HbA1c) were analysed in a sample of 394 men [...] Read more.
(1) Background: The study aimed to investigate the role of subclinical inflammation on the association between diurnal cortisol patterns and glycaemia in an aged population. (2) Methods: Salivary cortisol, interleukin-6 (IL-6) and glycated haemoglobin (HbA1c) were analysed in a sample of 394 men and 364 women (mean age = 5 ± 6.3, 65–90 years). The ratio of morning after awakening and late-night cortisol was calculated as an indication of diurnal cortisol slope (DCS). Multivariable regression models were run to examine whether IL-6 mediates the relationship between the DCS and glycaemia. The Sobel test and bootstrapping methods were used to quantify the mediation analyses. (3) Results: In comparison to normoglycaemic counterparts (n = 676, 89.2%), an increase in IL-6 concentrations, in individuals with hyperglycaemia (HbA1c ≥ 6.5%) (n = 82, 10.8%) (p = 0.04), was significantly associated with a flatter DCS. The link between flatter DCS and elevated HbA1c level was significant mediated by a heightened IL-6 level. Our results do not suggest reverse-directionality, whereby cortisol did not mediate the association of IL-6 with HbA1c. (4) Conclusions: In our sample, the relation between flatter DCS and hyperglycaemia was partly explained by IL-6 levels. The paradigm of subclinical inflammation-mediated cortisol response on glucose metabolism could have widespread implications for improving our understanding of the pathophysiology of type 2 diabetes mellitus. Full article
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15 pages, 1630 KiB  
Article
Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension
by Lisa-Marie Walther, Roland von Känel, Nadja Heimgartner, Claudia Zuccarella-Hackl, Ulrike Ehlert and Petra H. Wirtz
J. Clin. Med. 2021, 10(12), 2714; https://doi.org/10.3390/jcm10122714 - 19 Jun 2021
Cited by 2 | Viewed by 2170
Abstract
Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test [...] Read more.
Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p′s > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system. Full article
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18 pages, 643 KiB  
Article
Structural Equation Modeling of a Global Stress Index in Healthy Soldiers
by Tanja Maier, Melanie Kugelmann, Dae-Sup Rhee, Sebastian Brill, Harald Gündel, Benedikt Friemert, Horst-Peter Becker, Christiane Waller and Manuela Rappel
J. Clin. Med. 2021, 10(8), 1799; https://doi.org/10.3390/jcm10081799 - 20 Apr 2021
Cited by 2 | Viewed by 2626
Abstract
Accumulation of stress is a prognostic trigger for cardiovascular disease. Classical scores for cardiovascular risk estimation typically do not consider psychosocial stress. The aim of this study was to develop a global stress index (GSI) from healthy participants by combining individual measures of [...] Read more.
Accumulation of stress is a prognostic trigger for cardiovascular disease. Classical scores for cardiovascular risk estimation typically do not consider psychosocial stress. The aim of this study was to develop a global stress index (GSI) from healthy participants by combining individual measures of acute and chronic stress from childhood to adult life. One-hundred and ninety-two female and male soldiers completed the Perceived Stress Scale (PSS4), Trier Inventory for Chronic Stress (TICS), Hospital Anxiety and Depression Scale (HADS), Childhood Trauma Questionnaire (CTQ), Posttraumatic Diagnostic Scale Checklist (PDS), and the Deployment Risk and Resilience Inventory (DRRI-2). The underlying structure for the GSI was examined through structural equation modeling. The final hierarchical multilevel model revealed fair fit by taking modification indices into account. The highest order had a g-factor called the GSI. On a second level the latent variables stress, HADS and CTQ were directly loading on the GSI. A third level with the six CTQ subscales was implemented. On the lowest hierarchical level all manifest variables and the DRRI-2/PDS sum scores were located. The presented GSI serves as a valuable and individual stress profile for soldiers and could potentially complement classical cardiovascular risk factors. Full article
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13 pages, 894 KiB  
Article
Delayed Improvement of Depression and Anxiety after Transcatheter Aortic Valve Implantation (TAVI) in Stages of Extended Extra-Valvular Cardiac Damage
by Laura Bäz, Marisa Puscholt, Claudia Lasch, Mahmoud Diab, Sven Möbius-Winkler, P. Christian Schulze, Gudrun Dannberg and Marcus Franz
J. Clin. Med. 2021, 10(8), 1579; https://doi.org/10.3390/jcm10081579 - 8 Apr 2021
Cited by 7 | Viewed by 1725
Abstract
Background: Depression and anxiety are frequently occurring and likely to be linked to the severity of cardiac diseases like aortic stenosis (AS). This seems to be of interest since a staging classification of extra-valvular cardiac damage in AS has been introduced and shown [...] Read more.
Background: Depression and anxiety are frequently occurring and likely to be linked to the severity of cardiac diseases like aortic stenosis (AS). This seems to be of interest since a staging classification of extra-valvular cardiac damage in AS has been introduced and shown to be of prognostic relevance. Objective: The current study aimed to investigate the frequency of depression and anxiety in association to staging and their dynamics after transcatheter aortic valve implantation (TAVI). Methods: A total number of 224 AS patients undergoing TAVI were classified according to the 2017 staging classification into stage 0 to 4 and further dichotomized into group A (stage 0 to 2) and B (stage 3 and 4). Using the Hospital Anxiety and Depression Scale (HADS-D), patients were assigned to depressive versus non-depressive or anxious versus non-anxious per staging group respectively, and analyzed at baseline, 6 weeks, 6 months and 12 months after TAVI. Results: After dichotomization, 158 patients (70.5%) were assigned to group A and 66 patients (29.5%) to group B. The part showing pathologic values for depression was 25.4% (57/224 patients) in the entire collective, 26.6% (42/158 patients) in group A and 22.7% (15/66 patients) in group B (p = n.s.). The proportion showing pathologic values for anxiety was 26.8% (60/224 patients) in the entire collective and did not differ between group A (24.7%, 39/158 patients) and B (31.8%, 21/66 patients) (p = n.s.). In patients revealing pathologic values for depression or anxiety prior to TAVI, there were significant and stable improvements over time observable already in short-term (6 weeks) follow-up in group A, and likewise, but later, in long-term (6/12 months) follow-up in group B. Conclusions: Although of proven prognostic relevance, higher stages of extra-valvular cardiac damage are not associated with higher rates of pre-existing depression or anxiety. The TAVI procedure resulted in a persisting reduction of depression and anxiety in patients showing pathologic values at baseline. Notably, these improvements are timely delayed in higher stages. Full article
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12 pages, 680 KiB  
Article
Depression Associated with Reduced Heart Rate Variability Predicts Outcome in Adult Congenital Heart Disease
by Mechthild Westhoff-Bleck, Lars H. Lemke, Jan-Marc S. Bleck, Anja C. Bleck, Johann Bauersachs and Kai G. Kahl
J. Clin. Med. 2021, 10(8), 1554; https://doi.org/10.3390/jcm10081554 - 7 Apr 2021
Cited by 9 | Viewed by 2151
Abstract
In adult congenital heart disease (ACHD), major depressive disorder (MDD) represents a frequent comorbidity. In non-CHD, adverse outcome is predicted by MDD and heart rate variability (HRV), whereas in ACHD their prognostic relevance is unknown. We prospectively evaluated 171 patients (age 35.6 ± [...] Read more.
In adult congenital heart disease (ACHD), major depressive disorder (MDD) represents a frequent comorbidity. In non-CHD, adverse outcome is predicted by MDD and heart rate variability (HRV), whereas in ACHD their prognostic relevance is unknown. We prospectively evaluated 171 patients (age 35.6 ± 11.4 years; male 42.7%, mean observation time 54.7 ± 14.9 months). Binary regression analysis calculated the association between MDD and HRV. Cox proportional survival analysis estimated their impact on decompensated heart failure and all-cause mortality (HF/death), supraventricular and ventricular tachycardia (SVT/VT), and hospitalization due to unexpected cardiac causes. Exclusively MDD with moderate/severe symptoms showed significantly lower HRV as derived from frequency-domain analysis (Symindex) (p = 0.013). In multivariate Cox regression analysis, patients stratified according to the lower quartile of the Symindex comorbid with MDD (n = 16) exhibited poorer prognosis regarding HF/death (Hazard Ratio (HR): 7.04 (95%CI:(1.87–26.5)), SVT/VT (HR: 4.90 (95%CI:1.74–9.25)) and hospitalization (HR: 3.80 (95%CI:1.36–10.6)). An additional independent predictor was N-terminal pro-B-type natriuretic peptide elevation (p < 0.001), indicating advanced HF and heart disease complexity (p < 0.001). Autonomic nervous system dysfunction measured by altered HRV is considered to be one of the pathways linking MDD and adverse outcomes in cardiac diseases. Our results exceed the existing literature by demonstrating that MDD with decreased HRV is associated with poorer prognosis in ACHD. Full article
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10 pages, 635 KiB  
Article
Headache Is Associated with Low Systolic Blood Pressure and Psychosocial Problems in German Adolescents: Results from the Population-Based German KiGGS Study
by Melissa A. Centeno Córdova, Daniela Stausberg, Biyao Wang, Andreas Becker, Aribert Rothenberger, Christoph Herrmann-Lingen, Thomas Meyer and Julia Staab
J. Clin. Med. 2021, 10(7), 1492; https://doi.org/10.3390/jcm10071492 - 3 Apr 2021
Cited by 3 | Viewed by 1663
Abstract
Studies have reported controversial results on the relationship between headache and blood pressure. The aim of this post hoc study was twofold: first, to further investigate this relationship and, second, to assess the impact of psychosocial factors on this association in a population-based [...] Read more.
Studies have reported controversial results on the relationship between headache and blood pressure. The aim of this post hoc study was twofold: first, to further investigate this relationship and, second, to assess the impact of psychosocial factors on this association in a population-based study of German children and adolescents. The analysis was conducted on study participants aged between 11 and 17 years (n = 5221, weighted from the total study cohort) from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Health-related quality of life was assessed by self- and parent-rated German-language KINDL-R questionnaires (Children’s Quality of Life Questionnaire), while mental problems were analyzed using the Strengths and Difficulties Questionnaire (SDQ). Our findings confirmed that blood pressure was significantly lower in adolescents reporting episodes of headache than in those without headache (114.0 ± 10.2 mmHg vs. 115.5 ± 11.0 mmHg, p < 0.001). Logistic regression models adjusted to sex, age, body mass index, contraceptive use, and serum magnesium concentration demonstrated that headache was significantly associated with self-rated KINDL-R (Exp(B) = 0.96, 95% confidence interval (95% Cl) = 0.96–0.97, p < 0.001), parent-rated KINDL-R (Exp(B) = 0.97, 95% CI = 0.96–0.98, p < 0.001), as well as self-rated SDQ (Exp(B) = 1.08, 95% CI = 1.07–1.10, p < 0.001), and parent-rated SDQ (Exp(B) = 1.05, 95% CI = 1.04–1.06, p < 0.001). There was evidence that quality of life and mental problems mediated the effect of blood pressure on headache, as revealed by mediation models. Our results from the nationwide, representative KiGGS survey showed that low blood pressure is a significant predictor of headache, independent of quality of life and mental problems. However, these psychosocial factors may mediate the effect of blood pressure on headache in a still unknown manner. Full article
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14 pages, 1956 KiB  
Article
Systemic Catecholaminergic Deficiency in Depressed Patients with and without Coronary Artery Disease
by Uta Hoppmann, Harald Engler, Sabrina Krause, Edit Rottler, Julia Hoech, Franziska Szabo, Peter Radermacher and Christiane Waller
J. Clin. Med. 2021, 10(5), 986; https://doi.org/10.3390/jcm10050986 - 2 Mar 2021
Cited by 4 | Viewed by 2131
Abstract
Background: Stress and depression are known to contribute to coronary artery disease (CAD) with catecholamines (CA), altering the balance to a pro- and anti-inflammatory stetting and potentially playing a key role in the underlying pathophysiology. This study aimed to elucidate the impact of [...] Read more.
Background: Stress and depression are known to contribute to coronary artery disease (CAD) with catecholamines (CA), altering the balance to a pro- and anti-inflammatory stetting and potentially playing a key role in the underlying pathophysiology. This study aimed to elucidate the impact of social stress on the CA system and inflammation markers in patients suffering from CAD and depression. Methods: 93 subjects were exposed to the Trier Social Stress Test (TSST). Based on the results of the depression subscale of the Hospital Anxiety and Depression Scale (HADS, German Version) and the presence/absence of CAD, they were divided into four groups. A total of 21 patients suffered from CAD and depression (+D+CAD), 26 suffered from CAD alone (−D+CAD), and 23 suffered from depression only (+D−CAD); another 23 subjects served as healthy controls (−D−CAD). Subjects were registered at 09:00 AM at the laboratory. A peripheral venous catheter was inserted, and after a 60-min-resting period, the TSST was applied. Prior to and 5, 15, 30, and 60 min after the stress test, plasma epinephrine, norepinephrine, and dopamine concentrations (High Performance Liquid Chromatography (HPLC)) were measured together with the inflammation markers interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). High-sensitive C-reactive protein (hs-CRP, Enzyme-linked Immunosorbent Assay (ELISA)) was measured prior to TSST. Results: (+D−CAD) and (+D+CAD) patients showed significantly lower epinephrine and dopamine levels compared to the (−D+CAD) and (−D−CAD) participants at baseline (prior to TSST). Over the whole measurement period after the TSST, no inter-group difference was detected. Partial correlation (controlling for age, gender and Body Mass Index (BMI)) revealed a significant direct relation between MCP-1 and norepinephrine (r = 0.47, p = 0.03) and MCP-1 and epinephrine (r = 0.46, p = 0.04) in patients with −D+CAD at rest. Conclusions: The stress response of the CA system was not affected by depression or CAD, whereas at baseline we detected a depression-related reduction of epinephrine and dopamine release independent of CAD comorbidity. Reduced norepinephrine and dopamine secretion in the central nervous system in depression, known as ‘CA-deficit hypothesis’, are targets of antidepressant drugs. Our results point towards a CA-deficit in the peripheral nervous system in line with CA-deficit of the central nervous system and CA exhaustion in depression. This might explain somatic symptoms such as constipation, stomach pain, diarrhoea, sweating, tremor, and the influence of depression on the outcome of somatic illness such as CAD. Full article
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11 pages, 2764 KiB  
Article
Social Stress-Induced Oxidative DNA Damage Is Related to Prospective Cardiovascular Risk
by Christiane Waller, Dae-Sup Rhee, Michael Gröger, Manuela Rappel, Tanja Maier, Markus Müller, Edit Rottler, Katharina Nerz, Christopher Nerz, Sebastian Brill, Horst-Peter Becker and Peter Radermacher
J. Clin. Med. 2020, 9(11), 3783; https://doi.org/10.3390/jcm9113783 - 23 Nov 2020
Cited by 6 | Viewed by 2607
Abstract
Psychosocial stress increases cardiovascular risk, which coincides with enhanced oxidative DNA damage. Increased sympathetic tone-related catecholamine release causes oxidative stress, which contributes to catecholamine-related cardiotoxicity. Therefore, we tested the hypothesis whether acute psychosocial stress induces oxidative DNA damage, its degree being related to [...] Read more.
Psychosocial stress increases cardiovascular risk, which coincides with enhanced oxidative DNA damage. Increased sympathetic tone-related catecholamine release causes oxidative stress, which contributes to catecholamine-related cardiotoxicity. Therefore, we tested the hypothesis whether acute psychosocial stress induces oxidative DNA damage, its degree being related to the cardiovascular risk profile and depending on the sympathetic stress response. After assessment of the prospective cardiovascular Münster score (PROCAM) to determine the risk of acute myocardial infarction, 83 male and 12 female healthy volunteers underwent the Trier social stress test for groups (TSST-G). Heart rate variability was quantified by measuring the standard deviation (SDNN) and root mean square of successive differences (RMSSD) between normal-to-normal inter-beat intervals. Salivary α-amylase (sAA) activity was assessed as a surrogate for noradrenaline plasma concentrations. Oxidative DNA damage was determined using whole-blood single-cell gel electrophoresis (“tail moment” in the “comet assay”). A total of 33 subjects presented with a prospective risk of myocardial infarction (risk+) vs. 59 subjects without risk (risk-). The TSST-G stress significantly increased blood pressure, heart rate, and sAA in both groups, while oxidative DNA damage was only increased in the risk+ group. Immediately after the TSST-G, the “tail moment” showed significant inverse linear relations with both SDNN and RMSSD. Acute psychosocial stress may cause oxidative DNA damage, the degree of which is directly related to the individual cardiovascular risk profile and depends on the stress-induced increase in the sympathetic tone. Full article
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Review

Jump to: Research, Other

13 pages, 512 KiB  
Review
Surviving to Acute Myocardial Infarction: The Role of Psychological Factors and Alexithymia in Delayed Time to Searching Care: A Systematic Review
by Federica Sancassiani, Roberta Montisci, Antonio Preti, Pasquale Paribello, Luigi Meloni, Ferdinando Romano, Antonio E. Nardi and Mauro Giovanni Carta
J. Clin. Med. 2021, 10(17), 3813; https://doi.org/10.3390/jcm10173813 - 25 Aug 2021
Cited by 5 | Viewed by 2311
Abstract
The time from symptom onset to reperfusion is a critical determinant of myocardial salvage and clinical outcomes in patients with acute myocardial infarction (AMI). This time period could be delayed if people do not seek help promptly and/or if the health system is [...] Read more.
The time from symptom onset to reperfusion is a critical determinant of myocardial salvage and clinical outcomes in patients with acute myocardial infarction (AMI). This time period could be delayed if people do not seek help promptly and/or if the health system is not efficient in responding quickly and attending to these individuals. The aim of this study was to identify psychological factors associated with pre-hospital delay (PHD) or patients’ decisional delay (PDD) in people with an ongoing AMI. A search in PubMed/Medline from 1990 to 2021 with the keywords “pre-hospital delay” OR “prehospital delay” OR “patient delay” OR “decisional delay” OR “care seeking behavior” AND “psychological factors” OR “alexithymia” AND “myocardial infarction” was performed. Thirty-six studies were included, involving 10.389 patients. Wrong appraisal, interpretation and causal beliefs about symptoms, denial of the severity of the symptoms and high levels of alexithymia were found related to longer PHD or PDD. Alexithymia may be an overarching construct that explains the disparate findings of the studies exploring the role of psychological factors in PHD or PDD. Further studies are needed in order to analyse the role of alexithymia in patients with risk factors for AMI to prevent delay. Full article
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Other

Jump to: Research, Review

25 pages, 7962 KiB  
Perspective
H2S and Oxytocin Systems in Early Life Stress and Cardiovascular Disease
by Oscar McCook, Nicole Denoix, Peter Radermacher, Christiane Waller and Tamara Merz
J. Clin. Med. 2021, 10(16), 3484; https://doi.org/10.3390/jcm10163484 - 6 Aug 2021
Cited by 9 | Viewed by 3038
Abstract
Today it is well established that early life stress leads to cardiovascular programming that manifests in cardiovascular disease, but the mechanisms by which this occurs, are not fully understood. This perspective review examines the relevant literature that implicates the dysregulation of the gasomediator [...] Read more.
Today it is well established that early life stress leads to cardiovascular programming that manifests in cardiovascular disease, but the mechanisms by which this occurs, are not fully understood. This perspective review examines the relevant literature that implicates the dysregulation of the gasomediator hydrogen sulfide and the neuroendocrine oxytocin systems in heart disease and their putative mechanistic role in the early life stress developmental origins of cardiovascular disease. Furthermore, interesting hints towards the mutual interaction of the hydrogen sulfide and OT systems are identified, especially with regards to the connection between the central nervous and the cardiovascular system, which support the role of the vagus nerve as a communication link between the brain and the heart in stress-mediated cardiovascular disease. Full article
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