Ad Appels

Novel Conformation-Specific Antibodies Against Matrix γ-Carboxyglutamic Acid (Gla) Protein: Undercarboxylated Matrix Gla Protein as Marker for Vascular Calcification

Objective—Matrix γ-carboxyglutamic acid (Gla) protein (MGP), a vitamin K–dependent protein, is a potent in vivo inhibitor of arterial calcification. We hypothesized that low endogenous production of MGP and impaired carboxylation of MGP may contribute to the development or the progression of vascular disease. Methods and Results—Novel conformation-specific antibodies against MGP were used for immunohistochemistry of healthy and sclerotic arteries. In healthy arteries, MGP was mainly displayed around the elastin fibers in the tunica media. The staining colocalized with that for carboxylated MGP, whereas undercarboxylated MGP (ucMGP) was not detected. In atherosclerotic arteries, ucMGP was found in the intima, where it was associated with vesicular structures. In Mönckeberg’s sclerosis of the media, ucMGP was localized around all areas of calcification. The results indicate that ucMGP is strongly associated with vascular calcification of different etiologies. In a separate study, serum MGP concentrations in a cohort of 172 subjects who had undergone percutaneous coronary intervention were significantly reduced compared with an apparently healthy population. Conclusions—These data show that impaired carboxylation of MGP is associated with intimal and medial vascular calcification and suggest the essentiality of the vitamin K modification to the function of MGP as an inhibitor of ectopic calcification.

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.

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.

Effects of treating exhaustion in angioplasty patients on new coronary events : Results of the randomized exhaustion intervention trial (EXIT)

Background: Extreme fatigue is a common complaint in percutaneous coronary intervention (PCI) patients, and is associated with an increased risk for new cardiac events. The objective of the Exhaustion Intervention Trial (EXIT) was to determine whether a behavioral intervention on exhaustion reduces the risk of a new coronary event after PCI. Methods and Results: Seven hundred ten consecutive patients, ages 35 to 68 years, who felt exhausted after PCI were randomized into an intervention group and a usual-care group. The intervention was based on group therapy focusing on stressors leading to exhaustion, and on support for recovery by promoting rest and making rest more efficient. One month after PCI, 50% of the patients felt exhausted. The intervention reduced the odds of remaining exhausted at 18 months by 56% in those without a previous history of coronary artery disease (CAD) (OR = 0.44; 95% CI 0.29–0.66), but had no effect on exhaustion in those with a history of CAD (OR = 0.93; 95% CI 0.56–1.55; p = .78). The intervention did not reduce the risk of a new coronary event within 2 years (RR = 1.14; 95%CI 0.82–1.57). Post-hoc analyses suggest that the effect of the intervention was limited by a positive history of CAD, the presence of a chronic, painful condition (especially rheumatism), and by opposite effects on early and late cardiac events. Conclusion: A behavioral intervention in PCI patients has a beneficial effect on feelings of exhaustion. It could not be demonstrated that the intervention reduces the risk of a new coronary event within 2 years. PCI = percutaneous coronary intervention; CAD = coronary artery disease; MQ = Maastricht Questionnaire; MIVE = Maastricht Interview Vital Exhaustion; EXIT = Exhaustion Intervention Trial; CABG = coronary artery bypass graft; MI = myocardial infarction.

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 Nature of the Depressive Symptomatology Preceding Myocardial Infarction

Abstract 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 mens 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 Coxs 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.

Waking up exhausted as risk indicator of myocardial infarction

Abstract During the last decade several studies have indicated that sleep problems might belong to the risk indicators for coronary artery disease (CAD). For example, a 6-year follow-up study of >10,000 subjects revealed a risk of 2.04 for CAD in “poor” versus “good” sleepers. 1 Little is known about the types of sleep complaints that are associated with future CAD. One may speculate that trouble falling asleep is associated with CAD, because this is indicative of prolonged tension. Trouble staying asleep may be predictive for the same reason, or because it is indicative of a heart failure or nocturnal angina. Waking up tired may reflect an impaired sleep or an adverse effect of medication, angina pectoris or aging, and lose its predictive power when adjusted for these factors. Waking up tired may also indicate depression. Recent meta-analyses of the vast literature of personality factors and CAD have shown that, of all personality attributes, depression is the one most strongly associated with disease outcome. 2 Because early-morning tiredness is a major characteristic of depression it is predicted that problems falling asleep or staying asleep are not predictive of MI when controlled for waking up exhausted, but that the latter complaint remains predictive when controlled for complaints indicating problems in gaining or maintaining sleep (hypothesis I). Waking up exhausted may be a consequence of poor sleep. Statistically controlling for the influence of problems falling or staying asleep does not completely remove any possible effects of these problems on the feeling of being tired at waking up. To rule out any possibility that exhaustion on waking up is caused by a “bad night,” we also tested the hypothesis that those who wake up exhausted but do not have problems falling or staying asleep are at increased risk of myocardial infarction (hypothesis II).

Group Cohesion and Working Alliance: Prediction of Treatment Outcome in Cardiac Patients Receiving Cognitive Behavioral Group Psychotherapy

Background: Various definitions of both group cohesion and working alliance are used in theories on group psychotherapy, making the study of their relative contribution to the treatment outcome difficult. In this study, two different, nonoverlapping questionnaires were used to explore the relationship between group cohesion, working alliance and treatment outcome in a time-limited, structured cognitive behavioral group psychotherapy aiming at the reduction of coronary risk factors. Methods: After having undergone percutaneous transluminal coronary angioplasty, 42 patients were treated with the aim to reduce exhaustion, anxiety, hostility and depression. The newly developed Group Cohesion Questionnaire (GCQ) and the Helping Alliance Questionnaire (HAQ-II, measuring the bond between individual patients and the group psychotherapist) were administered after the fifth and tenth treatment session. Exhaustion, quality of life, anxiety, blood pressure and heart rate were measured before and after treatment. To test the relationship between the GCQ, the HAQ-II and outcome variables, Pearson Product-Moment correlations and hierarchical regression was applied. Results: Principal Component Analysis of the GCQ yielded two dimensions, the bond with the group as a whole and the bond with other group members. Hierarchical regression showed that both the bond with other group members and working alliance contributed significantly and independently to the prediction of posttreatment systolic and diastolic blood pressure as well as posttreatment quality of life (confidence). Conclusions: Conceptually and empirically, group cohesion and the working alliance may be considered to represent different relationships in a psychotherapy group, contributing in different ways to the treatment outcome in cardiac patients receiving cognitive behavioral group psychotherapy.

Herpes viruses, cytokines, and altered hemostasis in vital exhaustion.

Objective Infections with herpes viruses have been implicated in the pathogenesis of atherosclerosis. We tested the hypothesis that vital exhaustion (VE) is associated with multiple herpesvirus infections, such as herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus, and with an increase in pathogen burden (ie, the aggregated seropositivity to immunoglobulin G antibodies for herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus). In addition, we examined the association of VE and pathogen burden with measures of hemostasis and inflammation. Methods Blood samples were drawn from 29 men with VE and 30 male control subjects, all healthy and nonsmokers, to assess serological evidence of infection and measures of hemostasis and inflammation. Results VE is associated with a relatively high pathogen burden, altered hemostasis, and higher levels of cytokines, such as interleukin-6. Across all subjects, a relatively high pathogen burden was also associated with altered hemostasis but not with increased cytokine levels. The interaction of VE with pathogen burden revealed significant linear increases in measures of hemostasis and inflammation. Finally, immunoglobulin G antibody titer levels of individual herpesvirus infections were not associated with hemostatic measures or with cytokines. Conclusions We conclude that stress-related alterations in hemostasis and inflammation are not necessarily linked to one particular herpesvirus infection but rather to an increase in aggregated seropositivity to herpesvirus infections.

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.