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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fear, anger, and grief may precipitate myocardial ischemia and infarction. The prognosis of patients with inducible ischemia during mental stress is worse than in those without inducible ischemia. The sympathetic nervous system plays an important role in stress-associated changes in cardiovascular regulation and contributes to cardiovascular morbidity and mortality by inducing vasoconstriction and tachycardia, as well as arrhythmia. Hostility--previously termed type A personality--is often associated with sympathetic hyperreactivity to mental stress and carries an increased risk for atherosclerotic vascular disease. As endothelial dysfunction is an early manifestation of atherosclerosis, the impact of mental stress on endothelial function is also important. Acute mental stress induces prolonged endothelial dysfunction in healthy volunteers, which is prevented by selective endothelin A receptor antagonism. This represents an important link between mental stress and atherosclerotic vascular disease. In addition, patients with depression show hypercortisolemia, and changes in platelet function leading to a prothrombotic state. These findings help to explain the increased cardiovascular risk in patients with depression.
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PMID:[Pathophysiologic cardiovascular changes in stress and depression]. 1466 4

There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
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PMID:Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. 1498 10

Acute mental stress may contribute to atherosclerosis by affecting inflammation and coagulation; however, the crosstalk between inflammation and coagulation during stress has not been studied. In the present study, we investigated the association of plasma fibrinogen, plasma IL-6 (interleukin-6) and free salivary cortisol with the procoagulant marker D-dimer reflecting fibrin formation both over a 2-h period and in response to acute mental stress. Twenty-one male volunteers (mean age, 47+/-8 years) underwent the Trier Social Stress Test combining a 3-min preparation phase, a 5-min job interview and 5-min mental arithmetic test before an audience. IL-6, fibrinogen, D-dimer and cortisol were measured immediately before and after stress, and after 45 min and 105 min of recovery from stress. Two distinct areas under the curve were computed to obtain integrated measures of total protein activity over the entire 2-h period and of stress reactivity of proteins. IL-6 (P < 0.001), fibrinogen (P = 0.001), D-dimer (P = 0.021) and cortisol (P < 0.001) had all significantly changed across the four time points assessed, as determined by ANOVA. For the entire 2-h period, total fibrinogen activity (R2 = 0.33, P = 0.007) and total cortisol activity (DeltaR2 = 0.17, P = 0.034) explained 50% of the variance in total D-dimer activity. Stress-induced changes in fibrinogen (R2 = 0.47, P = 0.001) and IL-6 (DeltaR2 = 0.18, P = 0.008) together explained 65% of the variance in D-dimer reactivity to stress. Total fibrin formation was independently predicted by fibrinogen and hypothalamo-pituitary-adrenal activity. Pro-inflammatory and procoagulant changes with stress were associated. Aside from fibrinogen reactivity, IL-6 reactivity was an independent predictor of stress-induced fibrin formation.
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PMID:Different contribution of interleukin-6 and cortisol activity to total plasma fibrin concentration and to acute mental stress-induced fibrin formation. 1575 67

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
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PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

Until relatively recently, depression has been considered a purely "mental" disorder and therefore in the natural domain of psychologists and psychiatrists. However, recent epidemiological studies have revealed that aging, physical and psychological stress, chronic pain, several metabolic disorders such as insulin resistance and established diabetes, alcoholism, inflammatory conditions, and vascular disorders such as arterial hypertension all may be associated with depression. The present review examines some of these depression-associated factors and the mechanisms by which they might give rise to vascular disorders such as atherosclerosis, microcirculation endothelial dysfunction, and interstitial disturbances leading to organ damage. A number of disorders involving the circulation can lead progressively and insidiously to large artery rigidity, remodeling of peripheral arteries, and alterations of the microcirculation of large blood vessels. Perturbations in vasa vasorum blood flow may contribute to atherogenesis, in addition to the influence of numerous cellular events involved in inflammation (tumor necrosis factor alpha, interleukin 1 beta, etc). Since Hans Selye first described the neuroendocrine cascade generated by experimentally induced stress half a century ago, phenomena such as the axonal release of neurotransmitters (including serotonin), accumulation of metabolites such as homocysteine, platelet-activating factor, and nitric oxide also have been implicated in the pathogenesis of depression. Moreover, vascular consequences of depression such as heart rate and pulse pressure variations may lead to endothelial dysfunction in critical microcirculation networks (cerebral, myocardial, and renal) and initiate physicochemical alterations in interstitial compartments adjacent to vital organs. The appropriate use of ambulatory monitoring of vascular parameters, such as heart rate and pulse pressure, and eventually, early identification of genetic and metabolic markers may prove helpful in the early detection of events preceding and predicting the clinical manifestations of depression.
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PMID:Depression and cardiovascular disease: a reciprocal relationship. 1587 13

Acute mental stress induces a significant increase in plasma interleukin (IL)-6 levels as a possible mechanism for how psychological stress might contribute to atherosclerosis. We investigated whether the IL-6 response would habituate in response to a repetitively applied mental stressor and whether cortisol reactivity would show a relationship with IL-6 reactivity. Study participants were 21 reasonably healthy men (mean age 46+/-7 years) who underwent the Trier Social Stress Test (combination of a 3-min preparation, 5-min speech, and 5-min mental arithmetic) three times with an interval of 1 week. Plasma IL-6 and free salivary cortisol were measured immediately before and after stress, and at 45 and 105 min of recovery from stress. Cortisol samples were also obtained 15 and 30 min after stress. Compared to non-stressed controls, IL-6 significantly increased between rest and 45 min post-stress (p=.022) and between rest and 105 min post-stress (p=.001). Peak cortisol (p=.034) and systolic blood pressure (p=.009) responses to stress both habituated between weeks one and three. No adaptation occurred in diastolic blood pressure, heart rate, and IL-6 responses to stress. The areas under the curve integrating the stress-induced changes in cortisol and IL-6 reactivity were negatively correlated at visit three (r=-.54, p=.011), but not at visit one. The IL-6 response to acute mental stress occurs delayed and shows no adaptation to repeated moderate mental stress. The hypothalamus-pituitary-adrenal axis may attenuate stress reactivity of IL-6. The lack of habituation in IL-6 responses to daily stress could subject at-risk individuals to higher atherosclerotic morbidity and mortality.
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PMID:Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men. 1610 37

Coronary heart disease is the leading cause of death in Western society, and its development is associated with chronic stress and other psychosocial factors. Atherosclerosis, the disorder underlying this disease, is an inflammatory process in which leukocytes interact with structurally intact but dysfunctional endothelium of the arteries. Platelets play a key role in this process by binding to leukocytes and promoting their recruitment to the endothelium. Platelet-leukocyte interactions also stimulate the release of pro-inflammatory and pro-thrombotic factors which promote atherosclerosis. Elevated circulating levels of platelet-leukocyte aggregates have been reported in cardiac patients and in individuals of low socioeconomic status, a factor associated with chronic psychological stress. Increased platelet activation has also been observed in individuals prone to depression or hostility, and in people subject to high levels of work stress. Acute psychological stress increases circulating platelet-leukocyte aggregates in healthy individuals and this effect is prolonged in cardiac patients. Platelet activation may be a mechanism linking psychosocial stress with increased coronary risk, and may also play a role in the emotional triggering of acute coronary syndromes in patients with advanced coronary disease.
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PMID:Platelets, coronary heart disease, and stress. 1618 45

The pathophysiological mechanisms underlying the association between psychological stress and cardiovascular disease are unclear. Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are inflammatory cytokines playing a pivotal role in atherosclerosis. IL-1beta activates IL-6, and both cytokines are produced by peripheral blood mononuclear cells. One mechanism through which stress could promote atherosclerosis is by regulating mononuclear cell cytokine gene expression. We studied cardiovascular and cytokine responses in 32 healthy men participating in two 5-min mental tasks and in 10 controls. Blood pressure and heart rate, assessed using a Portapres-2, increased significantly following tasks in all participants. Plasma IL-6 levels, determined by ELISA, also increased following tasks, with maximum levels detected 2h post-stress. Quantitative RT-PCR analysis showed that mononuclear cell IL-1beta gene expression rose significantly at 30 min post-stress and remained elevated at 75 and 120 min. Increases in IL-1beta gene expression correlated positively with plasma IL-6 responses, cardiovascular responses, subjective stress ratings, and anxiety symptoms. No changes were detected in controls. Stress-induced activation of mononuclear IL-1beta is a novel mechanism potentially linking stress and heart disease. This mechanism could also play a role in other inflammatory diseases exacerbated by stress.
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PMID:Psychological stress activates interleukin-1beta gene expression in human mononuclear cells. 1621 25

Nicotine is a strong activator of the hypothalamus pituitary adrenal (HPA) axis. Smoking of only two cigarettes consistently activates the HPA axis of habitual smokers. However, while being a habitual smoker only induces small changes of basal HPA axis activity, smoking induces an attenuated responsiveness of the HPA axis to psychological stress, but not to injection of corticotropin releasing hormone (CRH) or physiological load. The latter points to alterations at hypothalamic or other central structures. The further consequences of decreased HPA axis responsiveness are discussed. Chronic inflammation of the airways is a common consequence of habitual smoking, and smokers often present with low-grade systemic inflammation, which may be mediated by HPA axis alterations. However, habitual smokers' monocytes are reported to show an increased sensitivity towards the inflammation suppressing effects of cortisol, while on the one hand, inflammation of the airways appears to be relatively resistant towards glucocorticoid treatment. In conclusion, this pattern of attenuated cortisol responses and decreased glucocorticoid sensitivity may be causally related to disinhibition of inflammatory processes and thereby further stimulate adverse health outcomes, such as airway inflammation or atherosclerosis.
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PMID:The hypothalamic-pituitary-adrenal (HPA) axis in habitual smokers. 1632 48

A longstanding hypothesis is that individuals who exhibit large increases in blood pressure during psychological stress are at risk for atherosclerosis. We tested whether blood pressure changes during psychological stress predict subsequent coronary calcification (CaC) in young healthy adults. We evaluated 2816 healthy black and white women, 20 to 35 years of age, from the Coronary Artery Risk Development in Young Adults Study, who were not using medication for hypertension or diabetes in 1987-1988. Participants completed video game and star tracing tasks while their blood pressure was recorded. Thirteen years later (2000-2001), they completed computed tomography measures of CaC. Overall 9.3% (261 of 2816) had CaC present at follow-up. Each 10 mm Hg change in systolic blood pressure during the video game was associated with a 24% increased odds of having CaC at follow-up (unadjusted odds ratio, 1.24; 95% CI, 1.06 to 1.46; P=0.008). This association persisted after adjustment for age, race, sex, education, smoking, alcohol, family history of myocardial infarction, smoking, daily alcohol consumption, body mass index, and resting or baseline blood pressure (odds ratio, 1.31; 95% CI, 1.08 to 1.58; P=0.006). Blood pressure changes during the star tracing task were not associated with subsequent CaC. Blood pressure changes during a video game predicted the presence of CaC 13 years later. To our knowledge, this is the first study that reports blood pressure reactivity to a stressor being related to calcification in the coronary arteries. Blood pressure reactivity may provide useful prognostic information about future risk beyond standard risk factors.
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PMID:Blood pressure reactivity to psychological stress and coronary calcification in the Coronary Artery Risk Development in Young Adults Study. 1646 51


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