Postnatal corticosteroid response in neonates < 32 weeks and relation with placental pathology.

Acute chorioamnionitis and maternal vascular malperfusion are associated with an increased risk of bronchopulmonary dysplasia. To prevent bronchopulmonary dysplasia, postnatal corticosteroids are given to preterm neonates. Clinical observations indicate not all neonates respond to corticosteroids, the so-called non-responders. This study aimed to investigate the association between placental pathology and short-term response to postnatal corticosteroids in neonates < 32 weeks postconceptional age at risk for bronchopulmonary dysplasia. All neonates < 32 weeks born between 2009 and 2016, receiving corticosteroids in the course of BPD, were included. The preterm neonates were divided into three groups depending on placental histology: acute chorioamnionitis, maternal vascular malperfusion, or no placental pathology. Respiratory support was assessed prior to treatment and at days 4 and 7. A responder was defined as extubation within 7 days after starting corticosteroid treatment. In total, 52% of the chorioamnionitis neonates, 67% of the maternal vascular malperfusion neonates, and 58% of neonates in the no pathology group were responders. The odds ratio for extubation was 0.53 (0.18-1.55) at day 4 and 0.66 (0.23-1.97) at day 7, in the chorioamnionitis group compared to the maternal vascular malperfusion. CONCLUSION: Short-term response to postnatal corticosteroids did not significantly differ between premature neonates born after acute chorioamnionitis, maternal vascular malperfusion, or no placenta pathology. However, a trend of better corticosteroid response in maternal vascular malperfusion neonates was found, potentially due to differences in prenatal pulmonary development and postnatal cortisol. WHAT IS KNOWN: • Bronchopulmonary dysplasia is related to chorioamnionitis and maternal vascular malperfusion. • Corticosteroids remain an important treatment in the course of bronchopulmonary dysplasia despite conflicting results and non-responsiveness in some preterm neonates. WHAT IS NEW: • Non-responsiveness might be related to differences in pulmonary inflammation and systemic cortisol due to predispositions triggered by chorioamnionitis or maternal vascular malperfusion. • Neonates born after maternal vascular malperfusion seem to respond better to postnatal corticosteroid treatment.

Assessment of vital exhaustion and identification of subjects at increased risk of myocardial infarction in general practice.

Vital exhaustion, a state characterized by unusual fatigue, loss of energy, increased irritability, and feelings of demoralization, is one of the cardiovascular risk factors. The authors investigated whether vital exhaustion contributes to the identification of subjects at increased risk of myocardial infarction in general practice. In this prospective cohort study, vital exhaustion was assessed with the Maastricht Interview on Vital Exhaustion. Other cardiovascular risk factors established were age, gender, systolic and diastolic blood pressure, total cholesterol, body mass index, smoking habits, cardiovascular disease, and diabetes mellitus. A Cox regression analysis was used. The subjects were adults (41-66 years) in an average Dutch village population. Outcome measures were fatal and nonfatal myocardial infarction. At the univariate level, vital exhaustion doubled the risk of myocardial infarction. The effect of exhaustion was confounded by gender; women had higher exhaustion scores and a lower incidence of myocardial infarction. With control for gender, age, systolic blood pressure, total cholesterol, smoking habits, self-reported cardiovascular disease, and diabetes mellitus, vital exhaustion almost tripled the risk of myocardial infarction. Assessment of vital exhaustion contributes to the identification of subjects at increased risk of myocardial infarction in general practice.

Vital exhaustion as a risk indicator for first stroke.

Fatigue is a common condition after stroke. An unresolved question is whether the fatigue is a consequence of the stroke or is one of the precursors. The authors' objective was to investigate whether vital exhaustion is a precursor of first stroke while controlling for other cardiovascular risk factors. The design was a prospective cohort study. Vital exhaustion was diagnosed with the Maastricht Interview Vital Exhaustion scale. The authors controlled for age, gender, diabetes mellitus, systolic and diastolic blood pressure, total cholesterol, body mass index, and smoking habits as possible confounders. Data were analyzed with Cox regression analysis. The subjects were adults ages 41-66 in an average Dutch village population. Outcome measures included first stroke. Vital exhaustion increased the risk of stroke by 13% per vital exhaustion point on the Maastricht Interview Vital Exhaustion scale. This value remained statistically significant after control for other risk factors. Total cholesterol, diastolic blood pressure, systolic blood pressure, diabetes mellitus, and smoking also increased the risk of stroke significantly. A state of exhaustion is one of the risk indicators for stroke. This means that the fatigue so often seen after stroke was already experienced by many patients before the occurrence of the stroke.

Inflammation, depressive symptomtology, and coronary artery disease.

OBJECTIVE: Many patients feel exhausted or depressed before the onset of an acute coronary event, but little is known about the origin of these feelings. We tested the hypothesis that the depressive symptomatology is associated with a reactivation of latent viruses and inflammation of a coronary vessel. METHODS: A blood sample was drawn and a biopsy sample was obtained from the coronary lesion of 15 exhausted and 15 nonexhausted patients treated with directional coronary angioplasty because of severe angina. Blood samples were analyzed to measure antibody titers against Chlamydia pneumoniae, cytomegalovirus, and the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. The biopsy sample was analyzed for the presence of IL-1beta and TNF-alpha. RESULTS: Exhausted/depressed patients had higher antibody titers against cytomegalovirus, higher levels of C. pneumoniae immunoglobulin G, and higher levels of IL-1beta and TNF-alpha. No associations between the mental state of a patient and cytokine mRNA in the biopsy sample were found. CONCLUSIONS: The findings indicate that the mental state of angioplasty patients is positively associated with serological markers of inflammation. It remains to be seen whether the inflammation causes feelings of exhaustion, whether exhaustion and depression set the stage for inflammation, or whether existing feelings of exhaustion are amplified by the inflammation.

Behavioral risk factors of sudden cardiac arrest.

OBJECTIVE: The purpose of this study was to investigate the association between sudden cardiac arrest (SCA) and the behavioral factors exhaustion and nonexpression of emotions. METHODS: Case-control study of 99 victims of SCA and 119 coronary controls, matched for gender and age. RESULTS: Victims of SCA were more often assessed as exhausted and as closed by their family members than controls. A significant interaction between exhaustion and closeness on the risk of SCA was observed. Those who were exhausted and did not express their emotions had a sevenfold greater risk of SCA. CONCLUSION: The behavioral factor of exhaustion and nonexpression of emotions may contribute to the identification of persons at elevated risk for SCA.

The nature of the depressive symptomatology preceding myocardial infarction.

Little is known about the nature of the depressive symptomatology preceding myocardial infarction (MI). Specification of the depressive symptomatology is important for the development of hypotheses about the biological mechanisms relating depressive symptoms to MI. To test the hypothesis that feelings of fatigue and loss of energy have the strongest predictive power of all depressive symptoms, the authors reanalyzed data from a prospective study of 3877 healthy men aged 40 to 65 years. The men's mental state was assessed using the Maastricht Questionnaire, a scale that measures vital exhaustion, which is characterized by unusual fatigue and lack of energy, increased irritability, and depressive symptoms, including demoralization. Oblique factor analysis was used to validate these dimensions. Results of Cox's regression analyses showed that the fatigue subscale has the strongest predictive power for incident MI and that depression and irritability subscales lose their predictive power when controlled for fatigue.

Inflammation and the mental state before an acute coronary event.

Feelings of exhaustion have been found to belong to the precursors of acute coronary events. Guided by the current views of the pathogenesis of acute coronary syndromes, a two-stage model describing a feedback relationship between mental state and the disease process is presented. According to the presented model prolonged exposure to stress results in a state of exhaustion leading to increased susceptibility to inflammatory diseases. Inflammation, in turn, amplifies feelings of exhaustion and malaise through cytokine release. Results of a study of 15 exhausted and 15 nonexhausted angioplasty patients, showing elevated levels of interleukin-1beta and tumour necrosis factor-alpha in the exhausted patients, give empirical support to this model.

Vital exhaustion as a risk factor of myocardial infarction: a case-control study in Venezuela.

In this study, 32 first myocardial infarction (MI) cases and 42 healthy controls were compared with respect to vital exhaustion (VE), a state characterized by loss of energy, increased irritability, and feelings of demoralization. This state has been found to precede the onset of cardiac events. Participants also responded to questionnaires on Type A behavior, anger expression (Anger In, Anger Out, and Anger Control), and positive and negative self-concept. Results showed that VE discriminated well between MI patients and controls (Odds Ratio [OR] = 15.42, 95% confidence interval = 3.92-60.67) even when controlling for age, smoking, and exercise. The odds ratio decreased to 12.34 when controlling for socioeconomic status. Groups also differed in Anger In but not in Anger Control, Anger Out, negative or positive self-concept. Anger In was correlated to VE in all participants pointing to the relevance of withholding emotions in relation to exhaustion. Exhaustion was strongly associated with negative self-concept in the MI cases group only but significantly discriminated between cases and controls when adjusted for negative self-concept. Summarizing, the results show that, as has previously been found in other countries, in Venezuela VE is a precursor of MI.

Depressive symptomatology and vital exhaustion are differentially related to behavioral risk factors for coronary artery disease.

OBJECTIVE: This study proposes to assess the differences of two psychosocial risk indicators for coronary artery disease (CAD), ie, depressive symptoms and vital exhaustion. METHOD: In a representative, stratified, nation-wide sample of the population of Hungary over the age of 16 years (N = 12,640), analyses were made of whether those risk indicators were differentially related to several illness behaviors (including history of cardiovascular treatment and cardiovascular sick days), cognitions, mood states, and socioeconomic characteristics that may generally be associated with increased CAD risk. The sample was stratified by age, sex, and composition of the population of all counties in Hungary. RESULTS: Although depressive symptoms and vital exhaustion correlated strongly, there were clear and significant differences in strength of association between depressive symptoms, vital exhaustion and several variables under study. Dysfunctional cognitions, hostility, lack of purpose in life, low perceived self-efficacy, illegal drug use, alcohol and drug abuse, several forms of subjective disability complaints and history of treatment because of congenital disorders, and chronic skin and hematological disorders were more often associated with depressive symptoms, whereas loss of energy, use of stimulants, chest-pain-related disabilities, history of treatment because of cardiovascular disorders, and self-reported cardiovascular sick days were significantly more often associated with vital exhaustion. CONCLUSIONS: Vital exhaustion and depressive symptomatology are differentially associated with relevant external criteria. Vital exhaustion is associated with perceived cardiovascular complaints and history of cardiovascular treatment, whereas depressive symptomatology seems to be more closely connected to disabilities and complaints related to alcohol, drug, and congenital-disorder, and to dysfunctional cognitions and hostility.

Cardioprotective effect of moderate drinking: possible mediation by vital exhaustion.

A curvilinear relationship between alcohol consumption and heart disease risk has often been demonstrated. A similar relationship was found between vital exhaustion (VE) and alcohol intake in 62 Japanese and 53 British healthy males. Vital exhaustion is a prodromal state for cardiac events. A possible connection between moderate social drinking, VE and heart disease is suggested.

Relationship of blood coagulation and fibrinolysis to vital exhaustion.

OBJECTIVE: Acute physical and psychological stressors affect blood coagulation and fibrinolysis, but little is known about hemostatic factors associated with chronic psychological stress. Prolonged psychological stress may end in a state of vital exhaustion, which has been shown to be a risk factor for first myocardial infarction and recurrent events after coronary angioplasty. The present study tested the hypothesis that vital exhaustion resulting from chronic psychological stress is associated with impaired fibrinolytic capacity and increased coagulation factors. METHODS: On the basis of a validated questionnaire and subsequent structured interview, a well-defined group of otherwise healthy exhausted men was recruited (N = 15) and compared with age-matched not-exhausted controls (N = 15). Fibrinolytic measures included tissue plasminogen activator (TPA) antigen and plasminogen activator inhibitor (PAI-1) activity, and as coagulation factors we examined factors VIIc, factor VIIIc, and fibrinogen. Control variables were: blood pressure, smoking status, triglycerides, cholesterol, and standard hematological measures. Samples were collected twice to correct for intraindividual fluctuations. Statistical analyses were performed using 2 x 2 mixed model analysis of variance with subsequent univariate testing. RESULTS: Vital exhaustion was associated with significantly elevated levels of PAI-1 activity (p = .023). The higher PAI-1 activity in exhausted subjects (median = 13.0 U/ml vs. 6.0 U/ml) was not accounted for by smoking status or serum lipids. No significant differences were observed in TPA antigen, factor VIIc, factor VIIIc, and fibrinogen. The groups did not differ in blood pressure, smoking status, triglycerides, cholesterol, or standard hematological measures. CONCLUSION: These data suggest a reduced fibrinolytic capacity in exhausted individuals. Therefore, the relationship between vital exhaustion and risk of myocardial infarction may be mediated in part by an imbalance between blood coagulation and fibrinolysis.

Depression and coronary heart disease: observations and questions.

The evidence that depressive symptomatology precedes the onset of the acute coronary syndromes and influences the course of disease after their manifestation is accumulating. However, we still are far short of proof that depression has a causal role in the etiology and pathogenesis of coronary heart disease (CHD). Some unsolved questions concern the causes and the nature of the depression preceding a first or recurrent cardiac event, the biological mechanisms relating depression and CHD, the time window of the exposure-disease association, and the power of therapy programs for depression to reduce the risk of a first or recurrent cardiac event.

The effect of a psychological intervention program on the risk of a new coronary event after angioplasty: a feasibility study.

Restenosis after successful percutaneous coronary angioplasty (PTCA) is a major problem because it occurs in 25% to 35% of all patients. Because psychological factors, especially anger and vital exhaustion, have been found to increase the risk of new cardiac events after PTCA, a behavioral intervention might contribute to the reduction of the risk of restenosis. To investigate the operational and methodological aspects of a behavioral intervention, and to estimate the effect size of the risk reduction, we did a feasibility study of angioplasty patients who remained exhausted after PTCA. Breathing therapy was used as the main method for intervention. Thirty patients who participated in the intervention program and 65 controls were followed during an average period of 16 and 18 months, respectively. It was observed that the intervention resulted in a significant decrease of the mean exhaustion scores and reduced the risk of a new coronary event (cardiac death, coronary artery bypass grafting, myocardial infarction, rePTCA, restenosis) by 50% (chi = 2.19; p = 0.13). These results indicate that a clinical trial to test the hypothesis that a reduction of vital exhaustion and hostility reduces the risk of a new cardiac event after PTCA, is feasible and merits the efforts required.

Behavioral-neuroendocrine-immunologic interactions in myocardial infarction.

An enduring state of exhaustion as opposed to chronic hostility-a long-term risk factor-has been found to be a more proximal precursor of myocardial infarction. The strength of the association with exhaustion suggests that this behavioral factor reflects not only a breakdown in adaptation to chronic stressors but also the disease process itself. Recent research on the pathogenesis of myocardial infarction lends credence to a role for immunological factors. herein, we outline a two-stage theoretical model, postulating a feedback relationship between behavior, associated neuroendocrine changes, immunological responses, and the pathogenesis of this disease. We propose a long-term first stage consisting of chronic hostility, prolonged occupational over-exertion, and exposure to other life stressors, terminating eventually in a much shorter second stage of 'vital exhaustion'. Stressor-associated neuroendocrine changes result in immunosuppression leading to reactivation of latent, systemic infections (such as cytomegalovirus) and potentially to autoimmune reactions as well. The consequent release of pro-inflammatory cytokines exacerbates fatigue and induces a stimulus for cytokine production in brain. This cytokine production stimulates a chronically activated, over-compensated limbic-hypothalamic-pituitary-adrenal axis, resulting in a dampened response, continued exhaustion, and a potential 'reverberating circuit' between behavior, neuroendocrine change, cytokine release and coronary artery occlusion, culminating in myocardial infarction.

Exhausted subjects, exhausted systems.

A state of 'vital exhaustion', characterized by unusual tiredness, increased irritability and feelings of demoralization has been found to preceed the onset of myocardial infarction and to increase the risk of a new coronary event after angioplasty. Probably this state reflects a decreased activity of the hypothalamic-pituitary-adrenal axis as part of an homeostatic reaction to prolonged stress and inflammation.

Why do imminent victims of a cardiac event feel so tired?

A state of vital exhaustion, characterised by unusual tiredness and lack of energy, increased irritability and feelings of demoralisation, has been found to be one of the precursors of myocardial infarction and other cardiac events. These feelings probably reflect decreased activity of the hypothalamic-pituitary-adrenal axis. Treatment of the conditions leading to this state of vital exhaustion might decrease the risk of a cardiac event.

The relationship between severity of coronary artery disease and vital exhaustion.

The present study investigates the association between the severity of coronary artery disease (CAD) and feelings of exhaustion. Vital exhaustion consists of three major components: lack of energy, increased irritability, and demoralization. Previous studies showed that exhaustion is of predictive value for first myocardial infarction (MI). However, these studies could not rule out that the state of exhaustion prior to MI was the result of underlying CAD. To examine this issue, severity of CAD and cardiac pump function were related to feelings of exhaustion in 307 patients who underwent coronary angiography. It was found that exhaustion, as assessed by means of the Maastricht Questionnaire (MQ), was not related to the severity of CAD (F = 1.17; p = 1.05). Furthermore, a poor left ventricular function did not relate to MQ scores (N = 138; F < 1; NS). On the other hand, clinical variables (duration of complaints, exercise performance, peripheral vascular disease, and dyspnea), use of medication (nitrates, beta-blocking agents, calcium antagonists, and diuretics), and demographic characteristics (gender and education) were associated with MQ scores. Multiple regression analysis showed that demographic variables (lower education, younger age, and female gender) were the predominant predictors of exhaustion. In addition, dyspnea, peripheral vascular disease, and the use of medication related significantly to exhaustion scores (R2 = 0.13; F = 4.8; p < 0.001). We conclude that neither the extent of CAD nor impaired cardiac pump function is related to feelings of exhaustion in patients referred for coronary angiography. Therefore, the previously reported association between exhaustion and future MI is not likely to be caused by underlying coronary disease.

Are multiple roles a risk factor for myocardial infarction in women?

This study examined whether multiple social roles are associated with an increased risk for a first myocardial infarction in a sample of Dutch women and whether there is evidence in favour of either the scarcity or the enhancement hypothesis about multiple roles. Subjects were 79 patients with a first myocardial infarction (MI), and they were compared with 90 hospital controls. Logistic regression analyses showed that multiple social roles do not constitute a risk factor for a first myocardial infarction. Classic risk factors seem to be more important. Neither the scarcity nor the enhancement hypothesis was confirmed in connection with a first myocardial infarction. However, the findings do support the enhancement hypothesis with regard to general health. In conclusion, the results indicate that multiple social roles do not constitute a risk factor for a first myocardial infarction in women.

Self-rated health and mortality in a Lithuanian and a Dutch population.

The hypothesis that the evaluation of one's health as poor is associated with mortality, independent of the results of a standardized medical examination, was tested in the Kaunas-Rotterdam Follow-Up Study. In this study two cohorts, one consisting of 2452 Lithuanian males and one of 3365 Dutch males, aged 45-60, were screened for cardiovascular risk factors in 1973, using identical protocols, and were followed for about ten years. Self-rated health was assessed by two direct questions: 'How would you assess your own health?' and 'What do you think of your own health compared to that of other men of your age?' as well as by a Semantic Differential Test of 'My Health'. In both cohorts a negative evaluation of one's health was associated with mortality, controlling for past or present heart disease, cardiovascular risk factors, parental life span, socio-economic and marital status. Especially the data with regard to the comparative question indicate that self-rated health is associated with mortality in men living in two different socio-cultural systems. The date suggest that a weak sense of mastery may explain the association between health perception and mortality.