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Brain, behavior, mental stress, and the neurocardiac interaction
... Previous studies showed that emotional status such as the trait and state of anger [5], anxiety [6], depression [7] could have great impact. Potential mechanisms may involve inflammatory responses, cortisol responses, fibrinogen responses, coagulation system, hypothalamic pituitary adrenal (HPA) [9,10]. Hammadah et al. [11] linked cardiac biomarker with MSIMI, presenting that patients with MSIMI had higher level of resting cTnI. ...
... Diabetes is considered as a risk factor of CAD, due to the dysfunction of micro-and macro-vascular damaged by hyperglycemia [38] via inflammation pathway. The sudden mental stress results in the lack of blood flow and oxygen, and thus causes myocardial ischemia [9]. Patients with diabetes, or post MI, or CABG, have worse cardiac conditions because of existing cardiac cell damage and microvascular dysfunction. ...
Background
The high prevalence of mental stress induced myocardial ischemia (MSIMI) causes double risk of adverse cardiac events in patients with MSIMI. However, multiple types of mental stress, diagnostic techniques, and diagnostic measurements may increase the complexity and heterogeneity in the assessment of MSIMI. Therefore, we performed this meta-analysis to assess the prevalence, associated factors, and diagnostic methods of MSIMI.
Methods
We systematically searched PubMed, EMBACE, Web of Science, CNKI, Wanfang through 1 Feb 2020 in English and Chinese. Review Manager (RevMan) Version 5.3 and Stata 12.0 were used for data analyses.
Results
Twenty articles were enrolled. The pooled estimates for the prevalence of MSIMI in CAD patients was 32%. Potential associated factors of MSIMI involved history of post myocardial infarction (MI), or coronary artery bypass graft (CABG) (RR: 1.29, 95% CI 1.00–1.66, P = 0.05; RR: 1.59, 95% CI 1.00–2.52, P = 0.05). Evidence supported that diagnostic methods could influence the prevalence of MSIMI. Significant differences of MSIMI prevalence were found in different types of mental stress (Public Speaking: 22%; Mental arithmetic: 26%; Anger recall: 34%; Two types: 37%; Three or more than three types: 43%, P = 0.02), diagnostic techniques (SPECT: 26%; RNV: 38%; ECG: 16%; Echocardiography: 41%; Two types: 43%, P < 0.0001), and diagnostic measurements (LVEF decrease: 19%; WMA: 51%; ST depression: 16%; MPD: 26%; Two or more than two measurements: 45%, P < 0.00001). Moreover, univariate meta-regression demonstrated that MSIMI was linked with mental stress (exp(b): 1.0508, SE: 0.0201, P: 0.018).
Conclusions
This meta-analysis implicated that patients with diabetes, post MI or CABG might be more vulnerable to MSIMI. However, the prevalence of MSIMI could be influenced by diagnostic methods, especially the adopted types of mental stress, diagnostic techniques and measurements. Therefore, it is necessary to formulate a standard diagnostic method for MSIMI, which should be adequate, assessable, and affordable worldwide.
Registration PROSPERO. Online Protocol: CRD42020162822.
... Network physiology has been suggested to bridge integrated physiological systems and subsystems [119]. In particular, the interaction between the brain and heart has attracted increasing attention, facilitating the diagnosis and treatment of cardiovascular and cerebrovascular diseases [120][121][122][123][124] as well as the development of new methodologies to study brain function and heartbeat dynamics [125,126]. Figure 4 provides a schematic diagram of the bidirectional brain-viscera interaction. ...
In psychosomatic medicine, a harmonious brain-body interaction is an important cornerstone of physical health. The modern brain-computer interface (BCI), an interaction between the brain and abiotic devices, provides the benefits for people with the help of powerful computers. Our newly proposed term brain-apparatus communication (BAC), acknowledges the unique value of the above two interactions and further describes their interdependence; how this interdependence permits better understanding of physical and psychological health and promotes the harmonious coexistence of people with the environment is worth exploring. This perspective article provides a general review of the three types of interactions and discusses the possible future trends.
... Moreover, incorporating psychosocial risk factors into the Framingham risk score improves the prediction of CAD [38]. In up to 50% of patients with stable CAD, ischemic responses are triggered not only by extremely severe emotional stress, but also by environmental challenges that may be encountered in everyday life [26,34,39]. In these patients, MSIMI occurs more frequently than exercise-induced myocardial ischemia and may also be present in those with no signs of myocardial ischemia during exercise. ...
Epidemiological studies have shown that a substantial proportion of acute coronary events occur in individuals who lack the traditional high-risk cardiovascular (CV) profile. Mental stress is an emerging risk and prognostic factor for coronary artery disease and stroke, independently of conventional risk factors. It is associated with an increased rate of CV events. Acute mental stress may develop as a result of anger, fear, or job strain, as well as consequence of earthquakes or hurricanes. Chronic stress may develop as a result of long-term or repetitive stress exposure, such as job-related stress, low socioeconomic status, financial problems, depression, and type A and type D personality. While the response to acute mental stress may result in acute coronary events, the relationship of chronic stress with increased risk of coronary artery disease (CAD) is mainly due to acceleration of atherosclerosis. Emotionally stressful stimuli are processed by a network of cortical and subcortical brain regions, including the prefrontal cortex, insula, amygdala, hypothalamus, and hippocampus. This system is involved in the interpretation of relevance of environmental stimuli, according to individual’s memory, past experience, and current context. The brain transduces the cognitive process of emotional stimuli into hemodynamic, neuroendocrine, and immune changes, called fight or flight response, through the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. These changes may induce transient myocardial ischemia, defined as mental stress-induced myocardial ischemia (MSIMI) in patients with and without significant coronary obstruction. The clinical consequences may be angina, myocardial infarction, arrhythmias, and left ventricular dysfunction. Although MSIMI is associated with a substantial increase in CV mortality, it is usually underestimated because it arises without pain in most cases. MSIMI occurs at lower levels of cardiac work than exercise-induced ischemia, suggesting that the impairment of myocardial blood flow is mainly due to paradoxical coronary vasoconstriction and microvascular dysfunction.
... The role of depressive, anxiety, and insomnia symptoms on adverse outcomes has been explained through biological and behavioral mechanisms. Hypothalamic-pituitary-adrenal axis hyperactivity [40], autonomic nervous system imbalances [41], altered inflammatory responses [42], and high platelet aggregability [43] have been considered the most important biological mechanisms underlying the relationship between depression, anxiety, and insomnia symptoms, and increased cardiac risk. Among behavioral mechanisms, smoking, poor physical activity, poor dietary habits, and, more importantly, low adherence to treatment, have been reported [44]. ...
Mandatory quarantine during the COVID-19 pandemic had substantial negative consequences on psychological health in the general population. Depression, anxiety, and insomnia were reported to increase the morbidity and mortality risk in cardiac patients after cardiac interventions. Nonetheless, a gap in the evidence appeared regarding the effects of COVID-19-related quarantine on psychological outcomes in patients after cardiac interventions. The present study aimed to longitudinally investigate the effects of quarantine on depressive, anxiety, and insomnia symptoms in a group of patients who underwent cardiac intervention. Seventy-three patients admitted for cardiac rehabilitation completed a psychological assessment before and a reassessment after the quarantine and were included in the quarantine group. The control group included 76 patients who completed both evaluations before the quarantine. Depressive (Beck Depression Inventory-II; BDI-II), anxiety (Beck Anxiety Inventory-II; BAI), and insomnia (Sleep Condition Indicator; SCI) symptoms were evaluated in both groups at one (assessment) and eight (reassessment) months after cardiac intervention. The statistical analyses revealed that at reassessment, the quarantine group showed higher global depressive, anxiety, and insomnia symptoms than the control group and increased cognitive symptoms of depression. A higher presence of clinically relevant depressed patients was seen in the quarantine group. The present results showed that the COVID-19-related mandatory quarantine negatively affected psychological outcomes in patients after cardiac intervention, increasing the probability for these patients to be depressed. This, in turn, could influence patients’ health in a critical period for morbidity and mortality risk. This underlines the priority of integrating and improving targeted mental health support as the pandemic continues, especially for cardiac patients.
... The literature investigating the potential mechanisms linking depression to CHD (17,18) suggests common causal pathways (19,20). Hypothalamic-pituitary-adrenal axis hyperactivity (21), altered inflammatory response (22), high platelet aggregability (23), and autonomic nervous system imbalance (24) have been considered as the most important biological mechanisms underlying the relation between depression and increased cardiac risk. ...
Objective:
Poor vagally-mediated heart rate variability (vmHRV) is a mechanism linking depression to coronary heart disease (CHD). Reduced vmHRV is also considered an index of emotion dysregulation - the frequent use of maladaptive emotion regulation strategies, one of the most important being expressive suppression - which is a key component of depression. Therefore, this study aimed to investigate the moderating role of expressive suppression in the relation between depression and vmHRV in patients with CHD.
Methods:
The sample included 235 patients with CHD (mean age = 61.6 years (SD = 9.8); 12% women) admitted to cardiac rehabilitation after a cardiac intervention. The Beck Depression Inventory-II (BDI-II) was administered to assess depressive symptoms. Emotion regulation strategies based on either expressive suppression or cognitive reappraisal were assessed through the Emotion Regulation Questionnaire (ERQ). Resting electrocardiographic recordings were collected for five minutes to compute HRV indices.
Results:
Expressive suppression moderated the relation between depressive symptoms and vmHRV (b = -0.03; p = .012). Patients with lower expressive suppression scores showed no association between depressive symptoms and vmHRV (b = -0.00, p = .94), whereas those with higher expressive suppression scores showed a significant negative association between depressive symptoms and vmHRV (b = -0.05, p = .015).
Conclusions:
The use of expressive suppression is likely to potentiate the relation between depressive symptoms and poor vmHRV, which could increase the cardiac risk in these patients. Targeting emotion regulation skills in cardiac rehabilitation programs may be useful for reducing the impact of depression in cardiac patients.
... In particular, depression and CHD share several biological mechanisms. Depressed patients have higher levels of biomarkers that promote atherosclerosis, reduced heart rate variability suggesting increased sympathetic activity, increased C-reactive protein, an indicator of increased inflammatory response, altered serotonergic pathways, and altered platelet aggregability (Carney et al. 1988;Lichtman et al. 2008;Sheps and Rozanski 2005;Soufer et al. 2002;Taylor 2010). It has also been postulated that CHD and depression have common genetic patterns related to serotonin and inflammatory responses (McCaffery et al. 2006). ...
Psychological adjustment following acute cardiac events such as acute myocardial infarction (AMI) and coronary artery bypass graft surgery (CABGS) has received increasing attention in the last three decades. While physical recovery remains the highest priority, psychological recovery is now considered a primary concern for health professionals working in cardiac rehabilitation and secondary prevention. The prevalence of anxiety and depression in people who have had a cardiac event is up to four times higher than in the general population. Post-event anxiety and depression both confer an increased mortality risk, highlighting the importance of identifying these patients early in order to ensure appropriate treatment. In recent years it has been recommended that all cardiac patients be screened for depression after a cardiac event. However, there are some inherent problems with routine depression screening, particularly if undertaken soon after the event. There are risks of both unnecessary treatment of patients with transient symptoms and non-identification of patients whose symptoms appear later after physical recovery. This chapter outlines evidence regarding the prevalence and impacts of anxiety and depression in cardiac patients and issues regarding depression screening. Some alternative ways of identifying patients at risk of depression are discussed.
... In particular, depression and CHD share several biological mechanisms. Depressed patients have higher levels of biomarkers that promote atherosclerosis, reduced heart rate variability suggesting increased sympathetic activity, increased C-reactive protein, an indicator of increased inflammatory response, altered serotonergic pathways, and altered platelet aggregability (Carney et al. 1988;Lichtman et al. 2008;Sheps and Rozanski 2005;Soufer et al. 2002;Taylor 2010). It has also been postulated that CHD and depression have common genetic patterns related to serotonin and inflammatory responses (McCaffery et al. 2006). ...
Psychological adjustment following acute cardiac events such as acute myocardial infarction (AMI) and coronary artery bypass graft surgery (CABGS) has received increasing attention in the last three decades. While physical recovery remains the highest priority, psychological recovery is now considered a primary concern for health professionals working in cardiac rehabilitation and secondary prevention. The prevalence of anxiety and depression in people who have had a cardiac event is up to four times higher than in the general population. Post-event anxiety and depression both confer an increased mortality risk, highlighting the importance of identifying these patients early in order to ensure appropriate treatment. In recent years it has been recommended that all cardiac patients be screened for depression after a cardiac event. However, there are some inherent problems with routine depression screening, particularly if undertaken soon after the event. There are risks of both unnecessary treatment of patients with transient symptoms and non-identification of patients whose symptoms appear later after physical recovery. This chapter outlines evidence regarding the prevalence and impacts of anxiety and depression in cardiac patients and issues regarding depression screening. Some alternative ways of identifying patients at risk of depression are discussed.
... The biological mechanisms of cardio-pathogenesis attributable to depression and anxiety are multifactorial and include the dysregulation of the hypothalamic-pituitary- adrenal axis,[69]–[71] reduced heart-rate-variability,[72]–[74] altered serotonergic pathways, inflammatory response[74] and altered platelet aggregability.[75] An earlier review suggested 20% of variability in CAD and depressive symptoms was attributable to common genetic factors and the authors speculated these could be related to inflammation and serotonin.[76] ...
Research to date indicates that the number of coronary artery bypass graft (CABG) surgery patients affected by depression (i.e., major, minor, dysthymia) approximates between 30% and 40% of all cases. A longstanding empirical interest on psychosocial factors in CABG surgery patients highlights an association with increased risk of morbidity in the short and longer term. Recent evidence suggests that both depression and anxiety increase the risk for mortality and morbidity after CABG surgery independent of medical factors, although the behavioral and biological mechanisms are poorly understood. Though neither depression nor anxiety seem to markedly affect neuropsychological dysfunction, depression confers a risk for incident delirium. Following a comprehensive overview of recent literature, practical advice is described for clinicians taking into consideration possible screening aids to improve recognition of anxiety and depression among CABG surgery patients. An overview of contemporary interventions and randomized, controlled trials are described, along with suggestions for future CABG surgery research.
... More precisely, several (although not unequivocal) lines of evidence suggest that exaggerated stressor-evoked cardiovascular reactions predict (1) an accelerated progression of atherosclerosis in humans and nonhuman primates; (2) the premature development of high blood pressure (hypertension) and other precursors to CHD; and (3) the likelihood of having a future coronary event (e.g., myocardial infarction) (Schwartz et al., 2003;Treiber et al., 2003). As reviewed below, however, the neurobiological or 'brain-body' pathways that couple the central nervous system processing of acute stressors with the peripheral expression of cardiovascular reactions implicated in CHD risk remain largely uncertain (Lane et al., 2009a;Lane et al., 2009b;Lovallo, 2005;Lovallo and Gerin, 2003;Soufer et al., 2002). Arguably, delineating these neurobiological pathways may aid not only in developing brain-based strategies for augmenting CHD risk stratification and prediction, but also in furthering a mechanistic understanding of stress-related processes contributing to CHD vulnerability. ...
An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the ‘brain-body’ pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala — as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the ‘brain-body’ pathways that mechanistically link stressful experiences with CHD risk.
... Muchas variables se han identificado como posibles factores de riesgo para desarrollar enfermedades cardiovasculares, entre ellos el estrés, desórdenes emocionales, rasgos de personalidad, depresión y pobre apoyo social (Krantz & McCeney, 2002;Kubsanzky, Davidson & Rozanski, 2005;Strike & Steptoe, 2004;Freasure-Smith et al., 2000;Soufer, Arrighi & Burg, 2002). A continuación se hablará de forma un poco más detallada de cada uno de los siguientes factores psicosociales: la ira/hostilidad, el estrés, la ansiedad, la depresión y la falta de apoyo social. ...
Coronary artery disease is one of the most common diseases worldwide and constitutes a significant public health problem with high mortality rates. Studies of risk factors for coronary disease have begun to emphasize the importance of psychosocial factors such as stress, anger/hostility, anxiety, depression, and lack of social support. This review article will define and describe each factor and its relationship with the development and progression of coronary disease. La cardiopatía isquémica es una de las enfermedades más frecuentes a nivel mundial y constituye un importante problema de salud pública debido a sus altas tasas de mortalidad. Dentro de los factores de riesgo para el desarrollo y la progresión de las cardiopatías isquémicas, las investigaciones han comenzado a reconocer la importancia de los factores psicosociales, tales como el estrés, el complejo ira/hostilidad, la ansiedad, la depresión y el bajo apoyo social. Esta revisión teórica busca dar cuenta de las evidencias que apoyan estos factores como elementos importantes de estudio en el desarrollo, curso y desenlace de la cardiopatía isquémica.
... Adicionalmente, se ha visto cómo los trastornos mentales tienen elevada prevalencia entre los pacientes con enfermedades médicas (Lowe, Grafe, Kroenke, et al, 2003), tal es el caso de enfermedades como la diabetes, donde se conoce que estas personas son dos veces más propensas a sufrir depresión (Anderson, Freedland, Clouse y Lustman, 2001; Gavard, Lutsman y Clouse, 1993; Ilczyszyn y Gurí, 2001; Pineda, et al., 2004; Talbot y Nouwen, 2000). El panorama se agrava cuando se observa que esta relación es bidireccional, esto quiere decir que la presencia de trastornos mentales aumenta el riesgo de complicaciones de la enfermedad de base; tal es el caso de la depresión en el paciente médicamente enfermo (Roca y Arroyo, 1996), donde se encuentra que su presencia se asocia con elevada morbimortalidad, de tal forma que el riesgo de muerte intrahospitalaria en este paciente puede ser entre 5 y 15 veces más que el paciente sin depresión (Von Ammon Cavanagh, Furlanetto, Creech y Powell, 2001); así como en el VIH (O'Cleirigh, Ironson y Smits, 2007), el cáncer (Mystakidou, Tsilika, Parpa, Galanos y Vlahos, 2007), la enfermedad cardíaca (Krantz y McCeney, 2002; Kubsanzky, Davidson y Rozanski, 2005; Strike y Steptoe, 2005; FreasureSmith et al., 2000; Soufer, Arrighi y Burg, 2002; Prakash, 2003), la diabetes (De Groot, Anderson, Freedland, Clouse y Lustran, 2000), el asma (Amigo, Fernández y Pérez, 2003), entre otras. Esta situación ha llevado a que autores como McWhinney y otros (citado por Rubin y Wessely, 2001) sugieran que la mejor manera de abordar estos cuadros sea el abandono del dualismo y la aceptación de la premisa de que es normal que las emociones se expresen mediante el cuerpo, tanto de manera consciente como de forma inconsciente, y cómo esta expresión puede estudiarse científicamente por disciplinas como la psiconeuroinmunología (Heinrichs y Gaab, 2007). ...
El concepto “psicosomático” trae consigo una pesada carga semántica que tiene sus raíces en el dualismo filosófico, acentuado en la propuesta cartesiana, que ha permeado la racionalidad moderna y con ella la concepción de la enfermedad, tanto en el campo de la medicina como de la psicología. En esta revisión teórica se expone una breve discusión en torno al concepto “psicosomático”, esbozando las
principales perspectivas en el abordaje de la relación mente-cuerpo. Se concluye como necesaria la revisión de las posiciones dualistas y la incorporación de una nueva mirada de las nociones de salud y enfermedad, a partir de la cual el concepto psicosomático se hace redundante.
... In line with previous speculations, it is possible the correlated patterns of heightened stressor-induced activation across these brain regions (summarized in Table 3) could account for greater blood pressure reactivity via functional interac- tions with subcortical and brain stem cell groups involved in cardiovascular control. 14,35 We note, however, that we did not find associations between individual differences in blood pressure reactivity and stressor-induced neural activation in other brain regions known to be involved in stress-related physiological control, including medial temporal areas (eg, amygdala), medial forebrain areas (eg, hypothalamus), and midbrain and brain stem areas (eg, periaqueductal gray and medulla). 8 These null findings may be because of the methodologic difficulty of using fMRI to image activity in these relatively smaller areas, which are susceptible to even slight movement artifacts and magnetic field distortions because of their close proximity to air-tissue interfaces. ...
Individuals who show exaggerated blood pressure reactions to psychological stressors are at increased risk for hypertension, atherosclerosis, and stroke. We tested whether individuals who show exaggerated stressor-induced blood pressure reactivity also show heightened stressor-induced neural activation in brain areas involved in controlling the cardiovascular system. In a functional MRI study, 46 postmenopausal women (mean age: 68.04; SD: 1.35 years) performed a standardized Stroop color-word interference task that served as a stressor to increase blood pressure. Across individuals, a larger task-induced rise in blood pressure covaried with heightened and correlated patterns of activation in brain areas implicated previously in stress-related cardiovascular control: the perigenual and posterior cingulate cortex, bilateral prefrontal cortex, anterior insula, and cerebellum. Entered as a set in hierarchical regression analyses, activation values in these brain areas uniquely predicted the magnitude of task-induced changes in systolic (DeltaR(2)=0.54; P<0.001) and diastolic (DeltaR(2)=0.27; P<0.05) blood pressure after statistical control for task accuracy and subjective reports of task stress. Heightened stressor-induced activation of cingulate, prefrontal, insular, and cerebellar brain areas may represent a functional neural phenotype that characterizes individuals who are prone to show exaggerated cardiovascular reactivity.
Background:
The EXCEL trial compared outcomes in patients with unprotected left main coronary artery disease (LMCAD) treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) using everolimus-eluting stents. While rates of death, stroke, and myocardial infarction were similar at 36 months, event timing and repeat revascularization rates differed by treatment group.
Objectives:
To understand the effects of revascularization strategy from the patient's perspective, we performed a prospective quality of life (QoL) sub-study alongside the EXCEL trial.
Methods:
Between September 2010 and March 2014, 1905 patients with LMCAD were randomized to undergo CABG or PCI, of whom 1788 participated in the QoL sub-study. QoL was assessed at baseline and 1, 12, and 36 months using the Seattle Angina Questionnaire, the SF-12, the Rose Dyspnea Scale, the Patient Health Questionnaire-8, and the EQ-5D. Differences between PCI and CABG were assessed using longitudinal random-effect growth curve models.
Results:
Over 36 months, both PCI and CABG were associated with significant improvements in QoL compared with baseline. At 1 month, PCI was associated with better QoL than CABG. By 12 months though, these differences were largely attenuated, and by 36 months, there were no significant QoL differences between PCI and CABG.
Conclusions:
Among selected patients with LMCAD, both PCI and CABG result in similar QoL improvement through 36 months, although a greater early benefit is seen with PCI. Taken together with the 3-year clinical results of EXCEL, these findings suggest that PCI and CABG provide similar intermediate-term outcomes for patients with LMCAD.
We performed a systematic review and meta-analysis to determine whether perioperative depression and anxiety are associated with increased postoperative mortality in patients undergoing cardiac surgery. MEDLINE and EMBASE were searched through January 2017 using PubMed and OVID, to identify observational studies enrolling patients undergoing cardiac surgery and reporting relative risk estimates (RREs) (including odds, hazard, or mortality ratios) of short term (30 days or in-hospital) and/or late all-cause mortality for patients with versus without perioperative depression or anxiety. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic RREs in the random-effects models. Our search identified 16 eligible studies. In total, the present meta-analysis included data on 236,595 patients undergoing cardiac surgery. Pooled analysis demonstrated that perioperative depression was significantly associated with increased both postoperative early (RRE, 1.44; 95% confidence interval [CI] 1.01-2.05; p = 0.05) and late mortality (RRE, 1.44; 95% CI 1.24-1.67; p < 0.0001), and that perioperative anxiety significantly correlated with increased postoperative late mortality (RRE, 1.81; 95% CI 1.20-2.72; p = 0.004). The relation between anxiety and early mortality was reported in only one study and not statistically significant. In the association of depression with late mortality, there was no evidence of significant publication bias and meta-regression indicated that the effects of depression are not modulated by the duration of follow-up. In conclusion, perioperative depression and anxiety may be associated with increased postoperative mortality in patients undergoing cardiac surgery.
An interesting syndrome called the takotsubo syndrome was described by Japanese investigators close to 20 years ago. It is characterized by the sudden development of chest pain, ECG changes, and cardiac decompensation in a postmenopausal woman who has just been through a severe emotional stress. The left ventricular contraction pattern resembles a takotsubo, a Japanese octopus fishing pot. With supportive care, these patients survive the episode. Their cardiac function returns to normal. It is likely that the emotionally induced catecholamine surge in an estrogen-deficient woman causes a combination of epicardial coronary artery constriction, constriction of the myocardial microvasculature, and produces a direct stunning effect on the left ventricular myocardium.
This exploratory study was designed to investigate the link between a client's heart rate variability (HRV) and the forming of a therapeutic alliance (TA) during psychotherapy. Change in HRV is associated with many psychological and physiological situations, including cardiac mortality. Cardiac effects were evaluated during therapy in 30 symptomatically anxious clients using HRV during six weekly 1-hour therapy sessions (S1-S6). Therapeutic index (TI), a measure of TA, was evaluated using skin conductance resonance between client and therapist. The Working Alliance Inventory provides a subjective measure of TA. State and trait anxiety and mood states were also assessed. Most HRV parameters were highest during S4. The sympathovagal balance was highest in S1 but stabilized after S2. In S4, TI was linked to high HRV parameters. Overall higher anxiety levels seem to be associated to lower HRV parameters. Conversely, in S4, high HRV parameters were linked to higher mood scores. This study found that a subjective measure of TA contradicted the physiological outcome. Results suggest that physiological data collected during therapy are a more accurate barometer of TA forming. These research findings suggest a need for further research identifying physiological markers in clients with a variety of mental health disorders over long-term therapy.
The psychological and neurological impact of cardiac surgery has been of keen empirical interest for more than two decades although reports showing the prognostic influence of depression on adverse outcomes lag behind the evidence documented in heart failure, myocardial infarction, and unstable angina. The paucity of research to date is surprising considering that some pathophysiological mechanisms through which depression is hypothesized to affect coronary heart disease (e.g., platelet activation, the inflammatory system, dysrhythmias) are known to be substantially influenced by the use of cardiopulmonary bypass. As such, cardiac surgery may provide a suitable exemplar to better understand the psychiatric mechanisms of cardiopathogenesis. The extant literature is comprehensively reviewed with respect to the deleterious impact of depression on cardiac and neuropsychological morbidity and mortality. Research to date indicates that depression and major depressive episodes increase major cardiovascular morbidity risk after cardiac surgery. The association between depressive disorders and incident delirium is of particular relevance to cardiac surgery staff. Contemporary treatment intervention studies are also described along with suggestions for future cardiac surgery research.
It has recently been recognized that atherosclerosis in all stages of development and progression— from the fatty streak to
the ruptured plaque causing a myocardial infarction (MI) is a specialized inflammatory response. The central role of inflammation
in atherosclerosis is underscored by the last two papers authored by the late Russell Ross, whose pioneering research and
writing shaped much of our understanding of the pathology during the last 30 yr. Both of these reviews asserted unequivocally
that “atherosclerosis is an inflammatory disease” (1,2).
Coronary artery disease (CAD) is a chronic, multifactor disease that has powerful contributing genetic components as well
as strong lifestyle components that increase the risk for the development and progression of the disease. Risk factors for
CAD have been historically divided into nonmodifiable, primary modifiable, and secondary modifiable factors. The primary focus
of medicine has been on the treatment of established CAD, and preventive efforts have more aggressively addressed areas in
which direct pharmacological intervention is available (1) (see Table 1). This is especially evident with respect to hypertension, hyperlipidemia, and antiplatelet aggregation therapy.
Evidence points to a significant role for psychological factors in the pathogenesis of cardiovascular disease (CVD). Mental
stress, including psychological, psychosocial, or emotional stress, is recognized as a risk factor for the development of
CVD. It also seems to contribute to the onset of—and can directly precipitate acute—coronary syndromes (ACS), fatal arrhythmias,
and acute heart failure.
Mental stress-induced myocardial ischemia (MSIMI) is common in patients with clinically stable coronary heart disease (CHD) and is associated with poor outcomes. Depression is a risk factor of MSIMI. The REMIT trial investigates whether selective serotonin reuptake inhibitor (SSRI) treatment can improve MSIMI. The rationale and outline of the study are described.
In this single-center randomized clinical trial, adult patients with clinically stable CHD are recruited for baseline mental and exercise stress testing assessed by echocardiography. In addition, psychometric questionnaires are administered, and blood samples are collected for platelet activity analysis. Patients who demonstrate MSIMI, defined by new abnormal wall motion, ejection fraction reduction ≥8%, and/or development of ischemic ST change in electrocardiogram during mental stress testing, are randomized at a 1:1 ratio to escitalopram or placebo for 6 weeks. Approximately 120 patients with MSIMI are enrolled in the trial. The stress testing, platelet activity assessment, and psychometric questionnaires are repeated at the end of the 6-week intervention. The hypothesis of the study is that SSRI treatment improves MSIMI via mood regulation and modification of platelet activity.
The REMIT study examines the effect of SSRI on MSIMI in vulnerable patients with CHD and probes some potential underlying mechanisms.
The connection between cardiovascular disease and psychosocial risk factors has been the subject of an ever-growing body of literature over the last 50 years. Studies on the role of negative emotions, personality traits, chronic stress and social determinants have brought to light their possible role in triggering acute coronary syndromes, although further studies are required to clarify controversial results regarding the association between cardiovascular risk and important psychological problems such as depression and anxiety. The recognition of the role of emotional events in acute coronary syndromes paved the way for provocation experiments, aimed at inducing mental stress in a controlled setting and then documenting reversible impairment of myocardial perfusion, depolarization anomalies and arrhythmias. This ultimately led to the formalization of the concept of mental stress-induced myocardial ischemia. Accumulating evidence on the mechanistic bases of such phenomena outline a wide range of central and peripheral physiological changes associated with emotions and behaviors, whose effects are exerted on the cardiovascular system, sympathetic nervous system and the hypothalamus-hypophysis neuroendocrine axis. This article outlines the main steps in the identification of psychological aspects as cardiovascular risk factors and emphasizes the relevance of emotional stress as a trigger of acute cardiovascular events. Finally, a description is provided of the pathophysiological mechanisms behind mental stress-induced myocardial ischemia and pathways connecting the heart and brain.
The Takotsubo Syndrome was first described by Japanese investigators approximately 20 years ago and has been increasingly recognized in all countries. It occurs almost exclusively in postmenopausal women and is triggered by a severe emotional stress. Severe chest pain is common and the electrocardiogram often mimics that seen with an acute myocardial infarction. An echocardiogram or a left ventriculogram resembles a Takotsubo, a Japanese octopus fishing pot. In Japanese 'Takotsubo' means a 'fishing pot for trapping octopus.' These traps have a round bottom with a narrow neck. When the octopus enters the Takotsubo it is most often trapped while the fisherman pulls the device to the surface. The syndrome is reversible and over the next several weeks to months all electrocardiographic and echocardiographic changes revert to normal. It is likely that the emotionally induced catecholamine surge in an estrogen-deficient woman causes a combination of epicardial coronary artery constriction, constriction of the myocardial microvasculature, and direct cardiomyocyte toxicity producing a temporary stunning effect on the left ventricular myocardium.
Vita. Thesis (Ph.D.)--UCLA, 2007. Includes bibliographical references (leaves 177-188).
“My life is in the hands of any rascal who chooses to put me in a passion.” — —Sir John Hunter
This quote from one of the major medical figures of the 18th century describes the association of his expression of anger to his experience of angina.1 In 1793, Dr Hunter was engaged in rancorous argument during the course of a faculty meeting and died suddenly. Narrative reports of angina pectoris in association with an individual’s experience of provocative, stressful circumstances, although not as dramatic as that made by Hunter, date from the time of Celsus to the dawn of modern medicine. These observations gave rise to the pioneering work of Rosenman et al2 on what they came to call “behavior pattern A.” Their work in turn encouraged others to pursue constitutional factors—the personality—that might give rise to risk for stress-related effects on the heart. The resulting literature on emotion, personality, and coronary artery disease (CAD) has, however, very often dealt with narrow concerns, without sufficient integration of biological and social variables that reflect the contextual nature of psychosocial stress. In addition, methodological drift in the conduct of studies on Type A and associated personality factors, combined with the failure in studies to account for concurrent progress in the care of the cardiac patient, produced results that conflicted with the earlier, promising findings.2 These issues have been discussed elsewhere.3 Hence, although we intuitively continue to link emotional factors and coronary syndromes, the nature of the link remains unclear.
One consequence of the conflicting research findings on stress, emotion, and coronary syndromes is the absence of a conceptual framework, which is necessary if an effect on clinical awareness and practice is to be realized. In our pursuit of this framework, few discriminators are available to guide our …
Summary A body of research published over the past 20 years has revealed much concerning the prevalence, pathophysiology, and prognosis
associated with MSI while also providing promising approaches to improving event-free survival rates in those who have this
form of ischemia. Although many important questions remain, we believe that the findings to date provide sufficient evidence
for the planning, development, and execution of a large-scale clinical trial. Such a trial would provide for not only further
testing of prognostic significance and treatment effects but also explorations into important remaining questions of pathophysiology
while elaborating possible additional modalities for treatment. Our collective expertise in nuclear cardiology provides an
opportunity to establish the diagnostic standardization, approach, and assessment of prognosis and treatment. We are in a
position to be thought leaders of a complex clinical manifestation of ischemia that has substantial clinical impact.
The anterior cingulate cortex presumptively regulates blood pressure reactions to behavioral stressors. There is little evidence in humans, however, that stressor-evoked changes in blood pressure correlate with concurrent changes in anterior cingulate activity. Using fMRI, we tested whether changes in mean arterial blood pressure correlate with ongoing changes in blood oxygen level dependent (BOLD) activation in 9 women and 11 men who completed a stressful Stroop color-word interference task. Higher mean arterial pressure during the Stroop task correlated with greater BOLD activation in two regions of the cingulate cortex (perigenual and mid-anterior) and in other networked brain regions, including the insula, thalamus, and periaqueductal gray. These results support the hypothesis that the anterior cingulate cortex regulates blood pressure reactions to behavioral stressors in humans.
The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly flexible operating characterisitics. Major drivers include two circadian drivers, two extra-hypothalamic networks controlling top-down (psychogenic) and bottom-up (systemic) threats, and two intra-hypothalamic networks coordinating behavioral, autonomic, and neuroendocrine outflows. These various networks jointly and flexibly control HPA axis output of periodic (oscillatory) functions and a range of adventitious systemic or psychological threats, including predictable daily cycles of energy flow, actual metabolic deficits over many time scales, predicted metabolic deficits, and the state-dependent management of post-prandial responses to feeding. Evidence is provided that reparation of metabolic derangement by either food or glucocorticoids results in a metabolic signal that inhibits HPA activity. In short, the HPA axis is intimately involved in managing and remodeling peripheral energy fluxes, which appear to provide an unidentified metabolic inhibitory feedback signal to the HPA axis via glucocorticoids. In a complementary and perhaps a less appreciated role, adrenocortical hormones also act on brain to provide not only feedback, but feedforward control over the HPA axis itself and its various drivers, as well as coordinating behavioral and autonomic outflows, and mounting central incentive and memorial networks that are adaptive in both appetitive and aversive motivational modes. By centrally remodeling the phenotype, the HPA axis provides ballistic and predictive control over motor outflows relevant to the type of stressor. Evidence is examined concerning the global hypothesis that the HPA axis comprehensively induces integrative phenotypic plasticity, thus remodeling the body and its governor, the brain, to yoke the needs of the body to the wants of the mind. Adverse side effects of this yoking under conditions of glucocorticoid excess are discussed.
Research suggests that acute and chronic stress are risk factors for the development and progression of coronary artery disease. Much of this work is multidisciplinary, using unfamiliar concepts deriving from disciplines other than cardiology and medicine. This article addresses and clarifies, for the cardiologist, some of the key concepts and issues in this area and provides an overview of evidence linking acute and chronic stress to cardiac pathology. Areas addressed include definitions and measurement of mental stress, methodological issues in stress research, and distinctions between stress and variables such as personality, emotion, and depression. Mental stress is a multifactorial process involving the environment, individual experiences and coping, and a set of neuroendocrine, autonomic, cardiovascular, and other systemic physiologic responses. There are difficulties identifying a single consensus physiologic stress measure because of individual differences in perceptions and physiologic response patterns. Nonetheless, important associations exist between mental stress and clinically relevant cardiovascular end points. As multidisciplinary research in this area continues, one major goal is the better integration of psychosocial knowledge and measures with cardiology research and practice.
Background~Ischemia during laboratory mental stress tests has been linked to significantly higher rates of adverse cardiac events. Previous studies have not been designed to detect differences in mortality rates.
OBJECTIVES
This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography.BACKGROUND
Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood.METHODS
Coronary vasomotion was assessed in 76 patients (average age 59.9 ± 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 μg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure.RESULTSMental stress resulted in significant BP and heart rate increases (p 0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rΔSBP = −0.26, rΔDBP = −0.30, rΔMAP = −0.29; p’s 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD.CONCLUSIONS
Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.
Objectives:
We sought to investigate the mechanism of a mental stress-induced fall in left ventricular ejection fraction (LVEF) in patients with coronary artery disease.
Background:
Mental stress induces a fall in LVEF in a significant proportion of patients with coronary artery disease. This is accompanied by an increase in heart rate, blood pressure and rate-pressure product. Whether the mental stress-induced fall in LVEF is due to myocardial ischemia, altered loading conditions or a combination of both is not clear.
Methods:
Left ventricular (LV) function was studied noninvasively by serial equilibrium radionuclide angiocardiography and simultaneous measurement of peak power, a relatively afterload-independent index of LV contractility, in 21 patients with coronary artery disease (17 men, 4 women) and 9 normal subjects (6 men, 3 women) at baseline, during mental stress and during exercise. Peripheral vascular resistance (PVR), cardiac output (CO), arterial and end-systolic ventricular elastance (Ea, Ees,) and ventriculoarterial coupling (V/AC) were also calculated. Patients underwent two types of mental stress-mental arithmetic and anger recall-as well as symptom-limited semisupine bicycle exercise.
Results:
Nine patients (43%) had an absolute fall in LVEF of > or = 5% (Group I) in response to at least one of the mental stressors, whereas the remaining patients did not (Group II). Group I and Group II patients were similar in terms of baseline characteristics. Both groups showed a significant but comparable increase in systolic blood pressure (15+/-7 vs. 9+/-10 mm Hg, p=0.12) and a slight increase in heart rate (7+/-4 vs. 8+/-7 beats/min, p=0.6) and a comparable increase in rate-pressure product (2.2+/-0.9 vs. 1.9+/-1.2 beats/min x mm Hg, p=0.6) with mental stress. However, PVR increased in Group I and decreased in Group II (252+/-205 vs. -42+/-230 dynes x s x cm(-5), p=0.006), and CO decreased in Group I and increased in Group II (-0.2+/-0.4 vs. 0.6+/-0.7 liters/min, p=0.02) with mental stress. There was no difference in the change in peak power (p=0.4) with mental stress. With exercise, an increase in systolic blood pressure, heart rate, rate-pressure product and CO and a fall in PVR were similar in both groups. Of the two mental stressors, anger recall resulted in a greater fall in LVEF and a greater increase in diastolic blood pressure. Exercise resulted in a fall in LVEF in 7 patients (33%). However, exercise-induced changes in LVEF and hemodynamic variables were not predictive of mental stress-induced changes in LVEF and hemodynamic variables. Conclusions. Abnormal PVR and Ea responses to mental stress and exercise are observed in patients with a mental stress-induced fall in LVEF. Peripheral vasoconstrictive responses to mental stress contribute significantly toward a mental stress-induced fall in LVEF.
OBJECTIVES
This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography.BACKGROUND
Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood.METHODS
Coronary vasomotion was assessed in 76 patients (average age 59.9 ± 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 μg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure.RESULTSMental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rΔSBP = −0.26, rΔDBP = −0.30, rΔMAP = −0.29; p’s < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD.CONCLUSIONS
Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.
This study assesses the prognostic value of mental stress-induced ischemic left ventricular wall motion abnormalities and hemodynamic responses in patients with stable coronary artery disease (CAD). Seventy-nine patients (76 men and 3 women) with prior positive exercise test results were exposed to mental arithmetic and a simulated public speech stress in 2 prior studies. Ischemic wall motion abnormalities were monitored using echocardiography or radionuclide ventriculography (RNV). During mental stress testing, new or worsened ischemic wall motion abnormalities to mental stress and exercise were ascertained, as were peak changes in blood pressure and heart rate to mental stress. The occurrence of subsequent cardiac events (including cardiac death, nonfatal myocardial infarction, or revascularization procedures) was ascertained. New cardiac events were observed in 28 of 79 patients (35%) after a median follow-up duration of 3.5 years (range 2.7 to 7.3). Survival analysis indicated that 20 of 45 patients with mental stress ischemia (44%) experienced new cardiac events more frequently than those without mental stress ischemia (8 of 34; 23%; p = 0.048). Type of cardiac event did not differ between mental stress-positive and stress-negative patients. After controlling for baseline blood pressure and study group status (echocardiography vs RNV), there was a significantly higher relative risk of subsequent events for patients with high versus low peak stress-induced diastolic blood pressure responses (RR = 2.4, confidence interval 1.1 to 5.2; p = 0.03). These results demonstrate that ischemic and hemodynamic measures obtained from mental stress testing may be useful in assessing prognosis in CAD patients with prior positive exercise test results.
Mental stress can cause angina in patients with coronary artery disease, but its effects on coronary vasomotion and blood flow are poorly understood. Because atherosclerosis affects the reactivity of coronary arteries to various stimuli, such as exercise, we postulated that atherosclerosis might also influence the vasomotor response of coronary arteries to mental stress.
We studied 26 patients who performed mental arithmetic under stressful conditions during cardiac catheterization. (An additional four patients who did not perform the mental arithmetic served as controls.) Coronary segments were classified on the basis of angiographic findings as smooth, irregular, or stenosed. In 15 of the patients without focal stenoses in the left anterior descending artery, acetylcholine (10(-8) to 10(-6) mol per liter) was infused into the artery to test endothelium-dependent vasodilation. Changes in coronary blood flow were measured with an intracoronary Doppler catheter in these 15 patients.
The response of the coronary arteries to mental stress varied from 38 percent constriction to 29 percent dilation, whereas the change in coronary blood flow varied from a decrease of 48 percent to an increase of 42 percent. The direction and magnitude of the change in the coronary diameter were not predicted by the changes in the heart rate, blood pressure, or plasma norepinephrine level. Segments with stenoses (n = 7) were constricted by a mean (+/- SE) of 24 +/- 4 percent, and irregular segments (n = 20) by 9 +/- 3 percent, whereas smooth segments (n = 25) did not change significantly (dilation, 3 +/- 3 percent; P less than 0.0002). Coronary blood flow increased by 10 +/- 10 percent in smooth vessels, whereas the flow in irregular vessels decreased by 27 +/- 5 percent. The degree of constriction or dilation during mental stress correlated with the response to the infusions of acetylcholine (P less than 0.0003, r = 0.58).
Atherosclerosis disturbs the normal vasomotor response (no change or dilation) of large coronary arteries to mental stress; in patients with atherosclerosis paradoxical constriction occurs during mental stress, particularly at points of stenosis. This vasomotor response correlates with the extent of atherosclerosis in the artery and with the endothelium-dependent response to an infusion of acetylcholine. These data suggest that in atherosclerosis unopposed constriction caused by a local failure of endothelium-dependent dilation causes the coronary arteries to respond abnormally to mental stress.
To assess the causal relation between acute mental stress and myocardial ischemia, we evaluated cardiac function in selected patients during a series of mental tasks (arithmetic, the Stroop color--word task, simulated public speaking, and reading) and compared the responses with those induced by exercise. Thirty-nine patients with coronary artery disease and 12 controls were studied by radionuclide ventriculography. Of the patients with coronary artery disease, 23 (59 percent) had wall-motion abnormalities during periods of mental stress and 14 (36 percent) had a fall in ejection fraction of more than 5 percentage points. Ischemia induced by mental stress was symptomatically "silent" in 19 of the 23 patients with wall-motion abnormalities (83 percent) and occurred at lower heart rates than exercise-induced ischemia (P less than 0.05). In contrast, we observed comparable elevations in arterial pressure during ischemia induced by mental stress and ischemia induced by exercise. A personally relevant, emotionally arousing speaking task induced more frequent and greater regional wall-motion abnormalities than did less specific cognitive tasks causing mental stress (P less than 0.05). The magnitude of cardiac dysfunction induced by the speaking task was similar to that induced by exercise. Personally relevant mental stress may be an important precipitant of myocardial ischemia--often silent--in patients with coronary artery disease. Further examination of the pathophysiologic mechanisms responsible for myocardial ischemia induced by mental stress could have important implications for the treatment of transient myocardial ischemia.
• Two hundred eighty-three patients admitted to cardiac care units for myocardial infarction at two urban teaching hospitals were interviewed 8 to 10 days after infarction and 171 were reinterviewed 3 to 4 months later. Initially, 45% met diagnostic criteria for minor or major depression, including 18% with major depressive syndromes. Depression was not associated with the severity of cardiac illness but was associated with the presence of noncardiac medical illnesses. Three to 4 months after infarction, 33% of patients met criteria for minor or major depression. The large majority of patients who initially met criteria for major but not minor depression showed evidence of depression at 3 months and most patients with major depression had not returned to work by 3 months. Treatment of major depressive syndromes after myocardial infarction may reduce chronicity and disability, while minor depressive syndromes may be similar to normal grief and tend to be self-limited.
(Arch Intern Med. 1989;149:1785-1789)
THE relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.
Background— Although previous research demonstrated an independent link between depression symptoms and cardiac mortality after myocardial infarction (MI), depression was assessed only once, and a dose-response relationship was not evaluated.
Methods and Results— We administered the Beck Depression Inventory to 896 post-MI patients during admission and at 1 year. Five-year survival was ascertained using Medicare data. We observed a significant long-term dose-response relationship between depression symptoms during hospitalization and cardiac mortality. Results remained significant after control for multiple measures of cardiac disease severity. Although 1-year scores were also linked to cardiac mortality, most of that impact was explained by baseline scores. Improvement in depression symptoms was associated with less cardiac mortality only for patients with mild depression. Patients with higher initial scores had worse long-term prognosis regardless of symptom changes.
Conclusions— The level of depression symptoms during admission for MI is more closely linked to long-term survival than the level at 1 year, particularly in patients with moderate to severe levels of depression, suggesting that the presumed cardiovascular mechanisms linking depression to cardiac mortality may be more or less permanent for them.
Objective
—To assess the clinical significance of mental stress—induced myocardial ischemia in patients with coronary artery disease (CAD).
Design and Setting
—Cohort study in outpatients in a tertiary care teaching hospital assessed at baseline and followed up for up to 5 years.
Subjects
—A total of 126 volunteer patients (112 men, 14 women; mean age, 59 years) with documented CAD and exercise-induced myocardial ischemia.
Outcome Measures
—Patients underwent baseline mental stress and exercise testing using radionuclide ventriculography and 48-hour Holter monitoring. Patients were subsequently contacted by mailed questionnaires or telephone to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. Logistic regression and Cox proportional hazards models were used to examine the prognostic value of the ischemic measures after adjusting for such potential confounding factors as age, baseline left ventricular ejection fraction (LVEF), and history of myocardial infarction.
Results
—Twenty-eight patients (22%) experienced at least 1 cardiac event. Baseline mental stress—induced ischemia was associated with significantly higher rates of subsequent cardiac events (odds ratio, 2.8; 95% confidence interval [CI], 1.0-7.7; P<.05). The LVEF change during mental stress was significantly related to event-free survival (risk ratio [RR], 2.4; 95% CI, 1. 12-5. 14; P=.02), controlling for age, history of prior myocardial infarction, and baseline LVEF. This relationship remained significant after controlling for electrocardiogram (ECG)—defined ischemia during exercise (RR, 2.2; 95% CI, 1.01-4.81; P<.05). The RR for ECG-defined ischemia during exercise testing was 1.9 (95% CI, 0.95-3.96; P=.07) and the RR for ambulatory ECG ischemia was 0.75 (95% CI, 0.35-1.64; P=.47).
Conclusions
—The presence of mental stress—induced ischemia is associated with significantly higher rates of subsequent fatal and nonfatal cardiac events, independent of age, baseline LVEF, and previous myocardial infarction, and predicted events over and above exercise-induced ischemia. These data suggest that the relationship between psychological stress and adverse cardiac events may be mediated by the occurrence of myocardial ischemia.(JAMA. 1996;275:1651-1656)
Background: The association of depression with cardiac events has been investigated mainly in community cohorts, in patients undergoing catheterisation, or in patients who have had myocardial infarction. We have assessed the effect of depression on outcomes after coronary artery bypass graft (CABG) surgery. Methods: In a prospective study, we followed up for 1 year 207 men and 102 women, who had undergone coronary artery bypass graft surgery. We assessed depression with a structured psychiatric interview (diagnostic interview schedule) and a questionnaire (Beck depression inventory) before discharge. Cardiac events included angina or heart failure that needed admission to hospital, myocardial infarction, cardiac arrest, percutaneous transluminal coronary angioplasty, repeat CABG, and cardiac mortality. Non-cardiac events consisted of all other reasons for mortality or readmission. Findings: 63 patients (20%) met modified diagnostic statistical manual IV criteria for major depressive disorder. At 12 months, 17 (27%) of these patients had a cardiac event compared with 25 of 246 (10%) who were not depressed (p<0.0008). Five variables had significant univariate associations with cardiac events: sex, living alone, low ejection fraction (<0.35), length of hospital stay, and depression. In a Cox proportional-hazard model with these five and two other variables of cardiac severity, major depressive disorder (risk ratio 2.3 [95% CI 1.17-4.56]), low ejection fraction (2.3 [1.07-5.03]), and female sex (2.4 [1.24-4.44]) were associated with adverse outcomes. Depression did not predict deaths or admissions for non-cardiac events. Interpretation: Depression is an important independent risk factor for cardiac events after CABG surgery.
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A circadian variation of sudden cardiac death has been documented, but its relation to individual time of awakening and possible triggering events has not been studied in the general population. By monitoring of mortality records in 4 cities and towns in Massachusetts, 148 potential cases of sudden cardiac death were identified. In 94 cases, the informants listed on the death certificates were contacted, the diagnosis of sudden cardiac death was established, and a telephone interview was completed within a mean of 19 days (range 8 to 28) after the death.The time of day of all 94 cases of sudden cardiac death (mean age 61 ± 9 years, 74% men) demonstrated a circadian variation (p < 0.05) with a peak from 9:00 A.M. to 12:00 noon. An analysis of time of death adjusted for individual wake-times of the decedents demonstrated an increased onset of sudden cardiac death during the initial 3-hour interval after awakening with a relative risk of 2.6 (95% confidence interval 1.6, 4.2) compared with other times of the day.The increased risk of sudden cardiac death soon after awakening suggests specific triggering factors or mechanisms that are particularly likely to occur during this time. The narrowing of the time interval during which the risk of sudden cardiac death is increased should facilitate the study of possible pathogenetic mechanisms and triggering factors of the disease and may aid in the design of more effective preventive strategies.
Objectives:
This study investigated whether mental stress-induced vasodilation mediated by endothelium-derived nitric oxide (NO) is defective in conditions with endothelial dysfunction, such as hypertension and hypercholesterolemia.
Background:
Vascular release of NO modulates the vasodilator response to mental stress in healthy subjects. Previous studies have shown that hypertensive and hypercholesterolemic patients have impaired endothelium-dependent vasodilation to pharmacologic agents due to decreased NO activity. However, whether this abnormality also operates in response to physiologic stimuli such as mental stress has not been defined.
Methods:
Forearm blood flow responses (plethysmography) to mental stress were compared in 12 normal subjects, 12 hypertensive patients and 10 hypercholesterolemic patients before and during NO synthesis inhibition with N(G)-monomethyl-L-arginine (4 micromol/min). Vascular responses to acetylcholine (7.5, 15 and 30 microg/min), an endothelium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 microg/min), an exogenous NO donor, were also assessed in each group.
Results:
During saline the vasodilator response to mental stress was significantly blunted in hypertensive (37+/-11%; p=0.01) but not in hypercholesterolemic (85+/-21%; p=0.78) patients compared with controls (93+/-15%). N(G)-Monomethyl-L-arginine administration significantly blunted mental stress-induced vasodilation in healthy subjects (p=0.004 vs. saline) and hypercholesterolemic patients (p=0.03 vs. saline), but not in hypertensive patients (p=0.69 vs. saline). The vasodilator effect of the highest dose of acetylcholine was similarly blunted in hypertensive (215+/-44%; p=0.02) and hypercholesterolemic (172+/-71%; p=0.02) patients compared with controls (364+/-34), whereas the vasorelaxing response to sodium nitroprusside was similar in the three groups.
Conclusions:
Hypertensive but not hypercholesterolemic patients have impaired NO-dependent vasodilation during mental stress. These findings may be accounted for by different mechanisms underlying endothelial dysfunction in these two conditions and might explain an increased susceptibility of hypertensive patients to vascular damage over repeated exposure to stressful situations.
Current evidence links psychosocial factors to exacerbation of diet-induced atherosclerosis in monkeys via activation of the sympathetic nervous system. However, it is uncertain whether these factors can potentiate initial lesion formation, and do so even in the absence of dietary provocation, and whether any such effects can be prevented by beta-adrenergic blockade. As endothelial injury has been considered an initiating event in atherogenesis, we studied the effect of psychosocial stress on endothelial integrity in 48 adult male cynomolgus monkeys (Macaca fascicularis). All animals were housed in 12 social groups of four monkeys each for 11 weeks. The monkeys in half of the groups were exposed to a socially unstable ('stressed') condition for 72 h and received saline (n = 8), a lipophilic beta1-blocker (metoprolol, 0.30 mg/kg per h; n = 8), or hydrophillic beta1-blocker (atenolol, 0.15 mg/kg per h; n = 8). The remaining six social groups were assigned to the socially stable (non-stressed) condition; for 72 h these animals all remained in their social groups and were similarly treated with saline (n = 8), metoprolol (n = 8), or atenolol (n = 8). The frequency of IgG-positive (injured) endothelial cells was estimated on en face (Häutchen) preparations from the thoracic aorta and coronary arteries. Psychosocial stress caused a significant increase in the number of injured endothelial cells in the circumostial areas of the descending thoracic aorta in the placebo group (0.3 vs. 0.8%, P < 0.02), an effect that had not been demonstrated previously. Moreover, beta-blockade significantly (P < 0.01) inhibited the stress effect, with no differences between the two beta-blocking agents. The number of injured endothelial cells in the non-branched portions of the aorta and coronary arteries were low and indistinguishable among groups; irregularities in the size and location of branching points in the coronary arteries precluded analysis of these sites. This study demonstrated that psychosocial stress induces endothelial injury, and that this effect is mediated via beta1-adrenoceptor activation.
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Psychological stressors of different natures can induce different shifts of autonomic control on cardiac electrical activity, with either a sympathetic or a parasympathetic prevalence. Arrhythmia occurrence, R-R interval variability, and plasma catecholamine elevations were measured in male wild-type rats exposed to either a social stressor (defeat) or a nonsocial challenge (restraint). Electrocardiograms were telemetrically recorded, and blood samples were withdrawn through jugular vein catheters from normal, freely moving animals. Defeat produced a much higher incidence of arrhythmias (mostly ventricular premature beats), which were mainly observed in the 60-s time periods after attacks. The social challenge also induced a much stronger reduction of average R-R interval, a lower R-R interval variability (as estimated by the time-domain parameters standard deviation of mean R-R interval duration, coefficient of variance, and root mean square of successive differences in R-R interval duration), and higher elevations of venous plasma catecholamines compared with restraint. These autonomic and/or neuroendocrine data indicate that a social stressor such as defeat is characterized by both a higher sympathetic activation and a lower parasympathetic antagonism compared with a nonsocial restraint challenge, which results in a higher risk for ventricular arrhythmias.
Clinical coronary heart disease (CHD) occurred in 257 subjects during eight to nine years of follow-up (average, 8 1/2 years) in a prospective study of 39- to 59-year-old employed men. Incidence of CHD was significantly associated with parental CHD history, reported diabetes, schooling, smoking habits, overt behavior pattern, blood pressure, and serum levels of cholesterol, triglyceride, and beta-lipoproteins. The type A behavior pattern was strongly related to the CHD incidence, and this association could not be explained by association of behavior pattern with any single predictive risk factor or with any combination of them.
The Iraqi missile attack on Israel provided a unique opportunity to study the effects of fright due to a perceived threat of annihilation on the incidence of acute myocardial infarction (MI) and sudden death among the civilian population. During the first days of the Gulf war we noted a sharp rise in the incidence of acute MI and sudden death in our area compared with five control periods. Patient population in the various study periods did not differ significantly in age, sex ratio, hospital mortality, or proportion of patients in whom the acute event was the first presentation of coronary disease. However, during the first period of the war there were more cases of anterior wall MI and more patients received thrombolytic therapy than during control periods. Despite the continuing missile threat, the incidence of acute MI reverted to normal after the initial phase of the Gulf war.
Sixty-six male university students were classified as Type A or B on the basis of the Structured Interview of Rosenman and as hostile or non-hostile on the basis of the Cook-Medley scale. Vascular production of prostacyclin and platelet thromboxane in response to a standard vessel injury was evaluated. Basal thromboxane production, measured as the primary metabolite, thromboxane B2, in blood oozing from the bleeding-time site, was highest among hostile Type A subjects with significantly lower thromboxane production in hostile Type Bs and all non-hostile groups combined. Following an exercise treadmill test hostile subjects produced more thromboxane than non-hostile ones, and hostile Type As had significantly shorter bleeding times than hostile Type Bs. No significant differences on any measure were observed following a stressful color naming task. The observed interaction of hostility and Type A behavior on bleeding time thromboxane formation links behavior to an adverse aspect of a thrombosis-related parameter thought to be involved in the genesis of cardiovascular disease.
The purpose of the present study was to determine whether and to what extent mental stress can reproduce the perfusion defects that are known to be induced by exercise. Twenty-four patients with recent myocardial infarction (New York Heart Association functional class I) and evidence of ischemic response were evaluated by means of SESTAMIBI scintigraphy performed once after exercise and then again within 2 days after mental arithmetic. Baseline, exercise, and mental stress planar scintigrams were divided into 15 segments, and each segment was reviewed and scored on a scale of 0 to 3 by experienced observers using circumferential profile analysis. Conflicting scores were resolved by consensus. Electrocardiographic abnormalities were found in 15 of 24 patients during exercise and in none during mental arithmetic. Chest pain was experienced by five patients during exercise and by none during mental stress. Twenty patients showed reversible perfusion defects during mental stress. Of the 360 pooled scintigram segments, 99 evidenced uptake defects during exercise, and 48 of these showed the same defects during mental stress. Twenty of the remaining 51 of 99 segments were adjacent to segments showing reversible hypoperfusion, suggesting milder hypoperfusion in these segments during mental arithmetic than during exercise. Furthermore, 10 segments showed reversible defects only during mental stress such that seven of these occurred in areas adjacent to those that had shown exercise-induced reversible perfusion defects, two occurred in areas that had shown fixed SESTAMIBI defects during exercise, and one occurred in a segment that had shown completely normal uptake during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Although agonist-induced desensitization of adrenergic receptors has been previously demonstrated, the regulation of adrenergic receptors during acute psychological stress has not been investigated in humans. We studied 30 first year medical students during final examination week and one month earlier. Platelet alpha 2 receptor binding was measured using 3H-yohimbine and leukocyte beta 2 receptor binding was measured with 125I-CYP (Iodocyanopindolol). During final examination week, platelet alpha 2-receptor binding affinity was significantly reduced, while levels of plasma catecholamines and reported anxiety were significantly increased, compared with the earlier period. Students showing the greatest increases in plasma norepinephrine and in reported anxiety also demonstrated the greatest reductions in alpha 2 receptor binding affinity. These data show that acute psychological stress can produce adrenergic receptor desensitization, possibly through increased levels of circulating norepinephrine.
The current study was designed to evaluate the effects of a disrupted social environment on the endothelial integrity of various vascular segments in male cynomolgus monkeys (Macaca fascicularis). Each of 20 single-caged adult monkeys was fed a diet comparable to a person's ingestion of 240 mg cholesterol/day for a 10-week baseline period and then was introduced as a stranger into a four-member social group for 3 days. Half of the monkeys received a beta-adrenergic blocking agent (metoprolol) via subcutaneous implant 2 days before and during group housing. The social manipulation produced persistent sympathetic arousal as evidenced by significantly elevated heart rates among untreated monkeys (p less than 0.01) but not among their metoprolol-treated counterparts, whose heart rate declined (p less than 0.05). After the social manipulation, all monkeys were necropsied and evaluated for endothelial incorporation of immunoglobulin G (as an indicator of cell death), endothelial cell replication, the presence of adherent leukocytes, and arterial low density lipoprotein permeability and concentration. At branching sites in the thoracic aorta, immunoglobulin G incorporation and endothelial cell replication were significantly greater in untreated monkeys than in metoprolol-treated monkeys (p less than 0.01 for both analyses); no differences existed at nonbranch sites. Endothelial cell replication in the coronary arteries (where immunoglobulin G incorporation was not examined) was also greater among untreated than among metoprolol-treated monkeys. No significant differences were observed between treatment groups in arterial low density lipoprotein permeability or leukocyte adherence; estimates of arterial low density lipoprotein concentrations were higher among untreated than among metoprolol-treated monkeys, but only in the abdominal portion of the aorta. These results indicate that social disruption is associated with both sympathetic nervous system arousal and indexes of endothelial dysfunction, effects that may be prevented by treatment with a beta-adrenergic blocking agent.
Adenylate cyclase and phospholipase C activity were examined in platelet membranes obtained from 19 male subjects with combat-related posttraumatic stress disorder (PTSD) and 35 age- and gender-matched healthy controls. Basal and forskolin-stimulated adenylate cyclase activity were significantly lower in the PTSD group whereas aluminum chloride plus sodium fluoride (AlCl3/NaF)- and prostaglandin E1 (PGE1)-stimulated responses were normal. There was no difference in phospholipase C activity between the two groups. The lower basal and forskolin-stimulated adenylate cyclase responses replicate a previous report and suggest that PTSD may be associated with an abnormality of the catalytic subunit of the receptor-adenylate cyclase complex.
Sites of uptake, storage, and metabolism of [18F]fluorodopamine and excretion of [18F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [18F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [18F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.
The in vivo quantification of myocardial muscarinic receptors has been obtained in six closed-chest dogs by using positron emission tomography. The dogs were injected with a trace amount of 11C-labeled methylquinuclidinyl benzilate (MQNB), a nonmetabolized antagonist of the muscarinic receptor. This was followed 30 minutes later by an injection of an excess of unlabeled MQNB (displacement experiment). Two additional injections of unlabeled MQNB with [11C]MQNB (coinjection experiment) and without [11C]MQNB (second displacement experiment) were administered after 70 and 120 minutes, respectively. This protocol allowed a separate evaluation of the quantity of available receptors (B'max) as well as the association and dissociation rate constants (k+1 and k-1) in each dog. The parameters were calculated by using a nonlinear mathematical model in regions of interest over the left ventricle and the interventricular septum. The average value of B'max was 42 +/- 11 pmol/ml tissue, the rate constants k+1, k-1, and Kd were 0.6 +/- 0.1 ml.pmol-1.min-1, 0.27 +/- 0.03 ml.pmol-1.min-1, and 0.49 +/- 0.14 pmol.ml-1, respectively, taking into account the MQNB reaction volume estimated to 0.15 ml/ml tissue. Although [11C]MQNB binding would appear irreversible, our findings indicate that the association of the antagonist is very rapid and that the dissociation is far from negligible. The dissociated ligand, however, has a high probability of rebinding to a free receptor site instead of escaping into the microcirculation. We deduce that the positron emission tomographic images obtained after injecting a trace amount of [11C]MQNB are more representative of blood flow than of receptor density or affinity. We also suggest a simplified protocol consisting of a tracer injection of [11C]MQNB and a second injection of an excess of cold MQNB, which is sufficient to measure B'max and Kd in humans.
The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased between 6:00 AM and 12:00 noon compared with other times of day (p less than 0.001). Myocardial infarction occurred 3.8 times more frequently between 8:00 and 9:00 AM (hour of maximum incidence) than between 12:00 midnight and 1:00 AM (hour of minimum incidence). Time of myocardial infarction based on clinical and enzymatic methods correlated well (r = 0.95). Patients with higher or lower left ventricular ejection fraction, higher or lower degree of wall motion abnormalities and residual stenosis of the coronary arteries, and one-, two-, or three-vessel disease exhibited a similar circadian pattern, suggesting that the morning is a risk period for patients with mild as well as severe coronary artery disease. Only the group of patients receiving beta-adrenergic blocking therapy before the event did not show an increased morning incidence of myocardial infarction. This observation may contribute to an understanding of the mechanisms by which beta-blockers reduce the incidence of myocardial infarction. Further investigation of physiologic changes occurring during the morning period of increased risk of myocardial infarction may lead to better understanding of the disorder. Design and timing of cardioprotective medication may play a crucial role in improving prevention of acute myocardial infarction.
Two hundred eighty-three patients admitted to cardiac care units for myocardial infarction at two urban teaching hospitals were interviewed 8 to 10 days after infarction and 171 were reinterviewed 3 to 4 months later. Initially, 45% met diagnostic criteria for minor or major depression, including 18% with major depressive syndromes. Depression was not associated with the severity of cardiac illness but was associated with the presence of noncardiac medical illnesses. Three to 4 months after infarction, 33% of patients met criteria for minor or major depression. The large majority of patients who initially met criteria for major but not minor depression showed evidence of depression at 3 months and most patients with major depression had not returned to work by 3 months. Treatment of major depressive syndromes after myocardial infarction may reduce chronicity and disability, while minor depressive syndromes may be similar to normal grief and tend to be self-limited.
Fifty-two patients undergoing cardiac catheterization and subsequently found to have significant coronary artery disease (CAD) were given structured psychiatric interviews before catheterization. Nine of these patients met criteria for major depressive disorder. All 52 patients were contacted 12 months after catheterization, and the occurrence of myocardial infarction, angioplasty, coronary bypass surgery and death was determined. Results of the study show that major depressive disorder was the best predictor of these major cardiac events during the 12 months following catheterization. The predictive effect was independent of the severity of CAD, left ventricular ejection fraction, and the presence of smoking. Furthermore, with the exception of smoking, there were no statistically significant differences between those patients with major depressive disorder and the remaining patients on any variable studied. The possible mechanisms relating major depressive disorder to subsequent cardiac events are discussed. It is concluded that major depressive disorder is an important independent risk factor for the occurrence of major cardiac events in patients with CAD.
Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and beta-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of alpha 1- and beta 1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.
3H-p-Aminoclonidine binding to platelets of patients with primary, unipolar major depressive disorder was compared to that of a normal healthy control population. The variances of platelet alpha 2-adrenoceptor Kd and Bmax values in patients were significantly greater than in the control group. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax value of the depressed group was significantly lower than that of controls. We propose that an abnormal platelet alpha 2-adrenoceptor density may be used as a biological marker for major depressive disorder.
This article has no abstract; the first 100 words appear below.
Furchgott and Zawadzki¹ first reported that endothelial cells have an obligatory role in the relaxation caused by acetylcholine in isolated rabbit arteries. This observation reconciled earlier contradictory findings of the powerful vasodilatory effect of acetylcholine in the intact organism, as compared with the contraction that it causes in spiral strips of isolated blood vessels in which the endothelium has been damaged or removed. There has followed an exponential growth in knowledge about the role of the endothelium in modulating the tone of the underlying smooth muscle in response to pharmacologic agents, physiologic stimuli, and disease.²³⁴ The function of the endothelium . . .
Paul M. Vanhoutte, M.D.
Mayo Clinic Rochester, MN 55905
Cigarette smoking is strongly associated with ischemic heart disease and acute coronary events. The effect of smoking a single cigarette on regional myocardial perfusion was studied in 13 chronic smokers with typical stable angina pectoris using positron emission tomography and rubidium-82 (82Rb). Findings were compared with the effects of physical exercise. After exercise, 8 patients (61%) had angina, ST depression and abnormal regional myocardial perfusion. Uptake of 82Rb increased from 49 +/- 8 to 60 +/- 7 in remote myocardium, but decreased from 46 +/- 3 to 37 +/- 5 in an ischemic area. The remaining 5 patients (39%) had homogeneous increases in 82Rb uptake without angina or ST depression. After smoking, 6 of the 8 patients with positive exercise test responses had a decrease in 82Rb uptake, from 47 +/- 3 to 35 +/- 6 in the same segment of myocardium affected during exercise. However, in contrast to exercise, the events during smoking were largely silent. The absolute decreases in regional 82Rb uptake after smoking occurred at significantly lower levels of myocardial oxygen demand than after exercise. This suggests that an impairment of coronary blood supply is responsible. Thus, in smokers with coronary artery disease, each cigarette can cause profound silent disturbances of regional myocardial perfusion that are likely to occur frequently during daily life. Such repeated insults may represent an important mechanism linking smoking with coronary events.
To determine if sudden cardiac death shows circadian variation, the time of day of sudden cardiac deaths in the Framingham Heart Study was analyzed. Analysis was based on mortality data collected in a standardized manner for the past 38 years for each death among the 5,209 persons in the original cohort. The necessary assumptions about the cause and timing of unwitnessed deaths were made in a manner likely to diminish the possibility of detecting an increased incidence of sudden cardiac death during the morning. In the Framingham study, analyses using these assumptions reveal a significant circadian variation (p less than 0.01) in occurrence of sudden cardiac death (n = 429), with a peak incidence from 7 to 9 AM and a decreased incidence from 9 AM to 1 PM. Risk of sudden cardiac death was at least 70% higher during the peak period than was the average risk during other times of the day. Further studies are needed to confirm this finding in other populations, to collect data regarding medications and to determine activity immediately before sudden cardiac death. Investigation of physiologic changes occurring during the period of increased incidence of sudden cardiac death may provide increased insight into its causes and suggest possible means of prevention.
To determine whether sudden cardiac death exhibits a circadian rhythm similar to that recently demonstrated for nonfatal myocardial infarction, we analyzed the time of day of sudden cardiac death as indicated by death certificates of 2203 individuals dying out of the hospital in Massachusetts in 1983. The data reveal a prominent circadian variation of sudden cardiac death, with a low incidence during the night and an increased incidence from 7 to 11 A.M. The pattern is remarkably similar to that reported for nonfatal myocardial infarction and episodes of myocardial ischemia. The finding that the frequency of sudden cardiac death is increased in the morning is compatible with hypotheses that sudden cardiac death results from ischemia or from a primary arrhythmic event. Further study of the physiologic changes occurring in the morning may provide new information supporting or refuting these hypotheses, thereby leading to increased understanding and possible prevention of sudden cardiac death.
The effects of acute and subacute psychological stress caused by a sudden general disaster on mortality from atherosclerotic heart disease (underlying cause) and cardiac events (proximate cause) were investigated by comparing total and cause-specific mortality during the days after a major earthquake in Athens in 1981 with the mortality during the surrounding month and the corresponding periods of 1980 and 1982. There was an excess of deaths from cardiac and external causes on the days after the major earthquake, but no excess of deaths from cancer and little, if any, excess of deaths from other causes. The excess mortality was more evident when atherosclerotic heart disease was considered as the underlying cause (5, 7, and 8 deaths on the first three days, respectively; background mean deaths per day 2.6; upper 95th centile 5) than when cardiac events in general were considered as the proximate cause (9, 11, and 14 deaths on the first three days, respectively; background mean 7.1, upper 95th centile 12).
The present study employed continuous blood withdrawal to examine epinephrine and norepinephrine responses to a cognitive stressor (mental arithmetic), active physical stressors (handgrip and knee bends), passive painful stressors (venipuncture and cold pressor), and a medical procedure that was considered nonstressful (blood pressure measurements). The data were analyzed by analysis of variance (ANOVA) and by time series analysis. The ANOVA indicated that epinephrine and norepinephrine increased significantly in response to the stressors. Epinephrine showed a greater increase to the cognitive stressor than to the others. Time series analysis, however, showed a more varied pattern. It indicated that the height and duration of response differed considerably across subjects and across interventions. The results from both analytic procedures are compared and discussed in terms of current hypotheses of catecholamine response.
High levels of hostility as assessed by a MMPI scale (Ho) have been found associated with increased levels of arteriographically documented coronary atherosclerosis. In this study we examined the relationship between hostility and subsequent health status in a 25-year follow-up of 255 medical students who completed the MMPI while in medical school. High Ho scores were found to be predictive of both clinical coronary disease incidence and total mortality.
Stress affects cognition in a number of ways, acting rapidly via catecholamines and more slowly via glucocorticoids. Catecholamine actions involve beta adrenergic receptors and also availability of glucose, whereas glucocorticoids biphasically modulate synaptic plasticity over hours and also produce longer-term changes in dendritic structure that last for weeks. Prolonged exposure to stress leads to loss of neurons, particularly in the hippocampus. Recent evidence suggests that the glucocorticoid- and stress-related cognitive impairments involving declarative memory are probably related to the changes they effect in the hippocampus, whereas the stress-induced catecholamine effects on emotionally laden memories are postulated to involve structures such as the amgydala.
Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported.
We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P < .05).
Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.