Does Anxiety Affect Survival in Patients with Coronary Heart Disease?

INTRODUCTION: Behavioral and physiological risk factors worsen the prognosis of coronary heart disease (CHD). Anxiety is known to be a psychological predictor of CHD. In this study, we investigated whether this factor is associated with all-cause mortality in CHD patients in the long term. METHODS: We studied 180 patients (mean age 60.6 SD 9.2 years, 26% women) with CHD from the Berlin Anxiety Trial (BAT) and the Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) study. Their cardiac and psychological risk profile was represented by standardized procedures, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. Mortality outcomes were assessed using a community-based registry. RESULTS: Of 180 patients, we obtained information on all-cause mortality in 175 (96.7%) after a mean follow-up of 12.2 years (range 10.4-16.6 years). Of all participants, 54.4% had prior myocardial infarction, 95.3% had percutaneous transluminal coronary angioplasty and 22.2% had prior coronary artery bypass graft. Most of the patients (98.4%) had New York Heart Association class I and II, 25.6% had diabetes and 38.2% were smokers. Patients had a mean HADS anxiety score of 9.7 SD 4.1 at study entrance. We found the highest HADS anxiety quartile all-cause mortality in 14%, 30.2% in the middle quartiles and 58.7% in the lowest quartile (chi2 20.8, p = 0.001). Related to psychological mechanisms, a low level of anxiety, seemed to be a significant predictor of all-cause mortality. We found no advantage for patients who had received psychosocial therapy in terms of survival. CONCLUSION: These first data confirmed our hypothesis about the association of psychological risk factors with the long-term outcome of CAD patients. Future studies will clarify whether the severity of disease, age or a particular type of coping or denial mechanism are associated with the presented outcome in low-anxious patients.

Behavioral factors predict all-cause mortality in female coronary patients and healthy controls over 26 years - a prospective secondary analysis of the Stockholm Female Coronary Risk Study.

OBJECTIVE: The prognosis of coronary artery disease (CAD) is related to its severity and cardiovascular risk factors in both sexes. In women, social isolation, marital stress, sedentary lifestyle and depression predicted CAD progression and outcome within 3 to 5 years. We hypothesised that these behavioral factors would still be associated with all-cause mortality in female patients after 26 years. METHODS: We examined 292 patients with CAD and 300 healthy controls (mean age of 56 ± 7 y) within the Fem-Cor-Risk-Study at baseline. Their cardiac, behavioral, and psychosocial risk profiles, exercise, smoking, and dietary habits were assessed using standardized procedures. Physiological characteristics included a full lipid profile, the coagulation cascade and autonomic dysfunction (heart rate variability, HRV). A new exploratory analysis using machine-learning algorithms compared the effects of social and behavioral mechanisms with standard risk factors. Results: All-cause mortality records were completed in 286 (97.9%) patients and 299 (99.7%) healthy women. During a median follow-up of 26 years, 158 (55.2%) patients and 101 (33.9%) matched healthy controls died. The annualized mortality rate was 2.1% and 1.3%, respectively. After controlling for all available confounders, behavioral predictors of survival in patients were social integration (HR 0.99, 95% CI 0.99-1.0) and physical activity (HR 0.54, 95% CI 0.37-0.79). Smoking acted as a predictor of all-cause mortality (HR 1.56, 95% CI 1.03-2.36). Among healthy women, moderate physical activity (HR 0.42, 95% CI 0.24-0.74) and complete HRV recordings (≥50%) were found to be significant predictors of survival. CONCLUSIONS: CAD patients with adequate social integration, who do not smoke and are physically active, have a favorable long-term prognosis. The exact survival times confirm that behavioral risk factors are associated with all-cause mortality in female CAD patients and healthy controls.

Depression, anxiety, and vital exhaustion are associated with pro-coagulant markers in depressed patients with coronary artery disease - A cross sectional and prospective secondary analysis of the SPIRR-CAD trial.

INTRODUCTION: A hyper-coagulant state is a biological mechanism that triggers cardiac events in patients with coronary artery disease (CAD). Depressive symptoms and anxiety predict an unfavourable course of CAD. The SPIRR-CAD-RCT examined the effects of a psychological intervention and provided the opportunity to explore cross-sectional associations between indices of psychological strain and coagulation parameters, as well as prospective changes in depression scores and coagulation parameters. METHODS: In this secondary analysis, we investigated 253 CAD patients (194 male; age m 58.9, SD 8.3 yrs.) with mild to moderate depression (≥8 on the HADS-D) at baseline and at follow-up 18 months later: TF, fibrinogen, D-dimer, VWF, FVII and PAI-1 and the course of depression (HAM-D), vital exhaustion (VE) and anxiety scores (HADS-A) were examined by ANOVA in the total and younger age groups (≤ 60). RESULTS: HAM-D at baseline was correlated with TF (corr. R2 = 0.27; F = 9.31, p = 0.001). HADS anxiety was associated with fibrinogen (corr. R2.20; F = 7.27, p = 0.001). There was no detectable therapeutic effect on coagulation. Fibrinogen and VWF decreased within 18 months (time effect; p = 0.02; p = 0.04), as did HADS-D in both treatment groups (p < 0.001). Fibrinogen decreased more in patients ≤60 years with high VE compared to low VE (interaction time x group, p = 0.01). CONCLUSIONS: This is the first study to show an association between TF and depression. Coagulation parameters as potential mediators of CAD progression correlated cross-sectionally with depression and anxiety and prospectively with VE. Further studies should replicate these correlations in depressed and non-depressed CAD patients. ISRCTN: 76240576; clinicaltrials.gov.

The effects of usual Care in Psychosocial Intervention Trials of patients with coronary artery disease: a systematic review.

BACKGROUND: Many intervention studies of coronary artery disease (CAD) have found health benefits for patients in the "treatment as usual" (TAU) group like in the specific psychotherapy group. In this pilot study, we wanted to examine and discuss the role and reasons for TAU effects. METHODS: By means of a systematic review, we examined the control conditions from psychotherapeutic RCTs with CAD patients related to depressive symptoms, mortality and recurrence rate of events. The review question was limited to factors influencing the TAU effectiveness in such psychotherapeutic outcome studies. RESULTS: We found a decrease in depressive symptoms in TAU patients (mean ES: 0.65) and very differing mortality and recurrence rates of events. The effects were dependant on the year the study was published (1986-2016), the follow-up time of the study (0.25-7.8 years) and the treatment arms. A small dose of additional counselling, medical attention, and teaching of therapeutic techniques with clinical competence may reinforce the therapeutic alliance. These factors would be possible moderators of control group efficacy related to the reduction in depressive symptoms and a decrease in mortality and events. CONCLUSION: In the reviewed studies, we found that the control condition was beneficial for CAD patients, but this benefit was highly variable. Specified psychotherapeutic interventions showed an additional independent effect of treatment on depression and effects on morbidity and mortality. There is a need to identify patients at risk of remaining depressed or under severe stress during usual care. These patients may require additional psychosocial intervention.

Gender differences in psychosocial outcomes of psychotherapy trial in patients with depression and coronary artery disease.

INTRODUCTION: The biological and psychosocial risk profile differs between women and men with coronary artery disease (CAD). Depressive symptoms and Vital Exhaustion (VE) predict an unfavourable course of CAD. The secondary analysis of the SPIRR-CAD trial offered the possibility to examine gender as exposure variable of the clinical and psychological situation at baseline and in a variety of psychosocial measures as outcomes. METHODS: In this trial, 450 men (78.9%) and 120 women (21.1%) with CAD (age ≤ 75 y), with mild to moderate depression (scoring ≥8 on the HADS), were randomized to usual care with or without a stepwise psychotherapy intervention. Beside clinical measures exhaustion and other indicators of depressive symptoms were collected at baseline and 18-month follow up. RESULTS: Men had more signs and symptoms of heart disease at baseline, whereas women had higher psychosocial burden (e.g. negative affect). Women were more likely to live alone, had lower educational levels and employment rates and higher levels of depression and exhaustion. The psychotherapy intervention differed as a function of gender: In women, VE decreased from 29.4 ±â€¯8.1 to 22.1 ±â€¯11.7 in the intervention group (IG) and from 29.2 ±â€¯8.2 to 25.1 ±â€¯11.3 in the control group (CG). In men VE decreased from 23.3 + -10.8 to 21.2 ±â€¯9.7 in the IG and from 23.6 ±â€¯10.7 to 19.3 ±â€¯11.3 in the CG (time x intervention x gender; F = 4.97; p = .026). DISCUSSION: Women had a higher psychosocial burden than men. VE compared to other rating instruments of depressive symptoms suggested a stronger response to the intervention in women. VE may help to understand gender differences in psychotherapeutic treatment studies of CAD. ISRCTN: 76240576; clinicaltrials.gov.

Socioeconomic factors in coronary artery disease - Results from the SPIRR-CAD study.

Low socio-economic status (SES) has been associated with an increased coronary risk in Western countries. All stress experiences are more pronounced in low SES patients with stress emanating from problems with family, job, or money. The SPIRR-CAD study offered an excellent opportunity to examine these risk factors in German speaking mildly and medium depressed patients. In the SPIRR CAD study, a German multi centre randomized clinical trial of 450 male and 120 female coronary patients, we examined the standard and psychosocial risk factor profiles in relation to SES, as assessed by educational level. All differences in risk factors between low and high SES were in the inverse direction. Of standard risk factors, only smoking was socially graded and more common in low SES. Of psychosocial factors and emotions, exhaustion showed the strongest and most consistent inverse social gradient, but also anger, anxiety and depression were socially graded. The findings suggest that in German patients, as in other national groups, social gradients in CHD risk are considerable. They can be ascribed to both psychosocial and to standard risk factors. In the present two years follow-up, the prospective significance of psychological and social risk factors was analyzed showing that emotional factors played an important role, in that low and high SES patients differed in the expected direction. However, the differences were not statistically significant and therefore firm conclusions from follow up were not possible. TRIAL REGISTRATION: ISRCTN 76240576; NCT00705965.

The European Network on Psychosomatic Medicine (ENPM) - history and future directions.

BACKGROUND: Within national and international societies of psychosomatic medicine the idea has emerged of bringing together and coordinating psychosomatic, behavioural, psychological and medical actions with common interests throughout Europe as a way to increase their scientific and political influence. METHODS: It was felt that there was a strong need and opportunity of a common and unifying forum for scientific exchange. RESULTS: It was considered desirable to exchange scientific thoughts and experiences in an open minded and boundless way, among individuals and societies, between disciplines and across borders. The course of ideas and discussions within the group of European psychosomatic scientists over 12 years is presented as an effort to combine strengths and actions supporting clinical psychosomatic research and medical practice in Europe. The fields of psycho-cardiology, quality in primary care, psycho-oncology, gastrointestinal psychosomatics, C/L Psychiatry, and Psychosomatics are examples of such positive developments. DISCUSSION: Several historic ideas are mentioned and the aims and advantages of the newly founded European Association of Psychosomatic Medicine are discussed. The advantages and virtues of a more powerful common European organisation of Psychosomatic Medicine and Psychiatric Consultation-Liaison are compared to continuing our work within the present Psychosomatic/Psychiatric and Behavioural fields. CONCLUSION: Psychosomatic and Behavioural Medicine have reached a strong position in Europe. There are studies in which the medical speciality is on equal terms with psychosomatic medicine representatives. There is a continuous need for scientific conferences, for teaching, and for better practice with patients. This could be coordinated by a network. Much energy and time is lost in isolated societies and countries. We want to focus our resources in scientific projects within the boundaries of a scientific network with the primary aim of developing psychosomatic scientific exchange.

[Interpersonal patterns in obese patients]. / Interpersonelle Muster bei Adipositaspatienten.

In the last decades the number of obese and pre-obese patients in Western industrial nations increased. Obese patients have been largely unsuccessful in losing weight over time, but the causes of their difficulties and the causes of their obesity have remained unclear. We examined whether the attachment style and its interaction with interpersonal processes would shed light on this question. We analyzed 107 obese or pre-obese patients before the start of a weight loss intervention program. We used the Adult Attachement Prototype Rating (AAPR)-interview and related questionnaires (Helping Alliance Questionnaire (HAQ), Inventory of Interpersonal Problems (IIP-D), Brief Symptom Inventory (BSI)). According to the AAPR-rating 54% of the patients were secure and 46% insecure attached. The results suggest that insecure attachment style has an impact on psychic strain in obese patients unrelated to weight, gender and age. Additionally the insecure attachment style influences the therapeutic alliance experienced by patients and the therapist.

Women's exhaustion and coronary artery atherosclerosis progression: The Stockholm Female Coronary Angiography Study.

OBJECTIVE: Vital exhaustion (VE) has been associated with incident and recurrent cardiac events. The present study investigated the impact of VE on coronary atherosclerosis progression for 3 years. We further aimed to detect the relative importance of the VE subcomponents, fatigue, and depressed mood. METHODS: 103 women (age range, 30-65 years) who had experienced an acute coronary event underwent quantitative coronary angiography at baseline and again after 3 years. VE and subcomponents were assessed using the Maastricht Questionnaire. RESULTS: VE correlated significantly with coronary artery diameter change for 3 years (r = -0.239, p = .015). When analyzed in quartiles, women of the highest VE level showed the most pronounced coronary artery luminal diameter narrowing (mean = 0.21 mm, 95% confidence interval [CI] = 0.15-0.27), women in the third quartile were intermediate (mean = 0.11 mm, 95% CI = 0.05-0.17), and women within the two lower quartiles showed no significant change. High levels of the depressed mood and fatigue subscales were also associated with coronary artery diameter narrowing (mean = 0.19 mm, 95% CI = 0.12-0.26, p = .003; and mean = 0.17 mm, 95% CI = 0.08-0.26, p = .03, respectively). However, the associations were attenuated when both variables were entered into the model simultaneously: 0.17 mm (95% CI = 0.09-0.25, p = .05) and 0.14 mm (95% CI = 0.03-0.25, p = .67), respectively. CONCLUSIONS: VE was associated with accelerated coronary atherosclerosis progression in relatively young women who had experienced an acute coronary event. This association was mainly driven by depressed mood.

Anxiety as predictor of the cortisol awakening response in patients with coronary heart disease.

BACKGROUND: Anxiety is associated with worse outcomes in patients with coronary heart disease (CHD). A dysregulation of the HPA axis is a potential mechanism linking psychological factors and coronary disease. No study has yet investigated the relationship between anxiety and cortisol among patients with established CHD. PURPOSE: The aim of this study was to assess the association between anxiety and the cortisol awakening response in patients with CHD. METHOD: Four salivary cortisol samples were used to assess two measures of the cortisol awakening response (CAR) in 47 patients with established CHD. Anxiety was measured using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Higher anxiety values were associated with a higher total output of cortisol in the first hour after awakening (AUCg, area under the curve with respect to ground) (p = 0.04) and a nonsignificant trend towards a more pronounced increase (AUCi, area under the curve with respect to increase) (p = 0.08). In patients who had a history of myocardial infarction (MI), the cortisol output was lower compared to patients who had no previous MI (p = 0.02). In linear regression analyses, anxiety emerged as significant predictor of AUCg and AUCi after controlling for MI, ejection fraction (LVEF, left ventricular ejection fraction), and depression. CONCLUSIONS: Our results provide further indications for an association between anxiety and a dysregulation of the HPA axis. History of MI emerged as second predictor of cortisol output in the morning.

[C reactive protein in women with coronary heart disease and its association with depression]. / C-reaktives Protein bei Frauen mit koronarer Herzkrankheit und Zusammenhange mit Depressivitat.

OBJECTIVES: Depression is associated with increased risk and poor outcome of coronary heart disease (CHD), though the mechanisms are largely unknown. Low-grade inflammation offers a possible biological pathway, which has been confirmed in men but not in women. METHODS: We studied the association of C reactive protein (CRP), a biomarker of inflammation, with depressive symptoms in 292 women with CHD and 300 healthy age-matched controls, considering confounder variables (BMI, age, HDL cholesterol, triglycerides, menopausal status). CRP was measured by a high sensitivity assay. RESULTS: In the overall sample no significant association was found between depressive symptoms and CRP, whereas in the control group women with 2 or more versus 0-1 depressive symptoms showed heightened CRP (p = 0.005); there was no significant difference in CRP levels between CHD patients with 0-1 versus 2 or more depressive symptoms. Women with CHD had higher serum levels of CRP and more depressive symptoms than did controls. CONCLUSIONS: Contrary to men and healthy controls there was no link between CRP and depressive symptoms in women with CHD. More research is needed on how the harmful effects of depression are mediated, especially in women.

Behavioral interventions for coronary heart disease patients.

INTRODUCTION: There is a strong clinical need to provide effective stress reduction programs for patients with an acute coronary syndrome. Such programs for men have been implemented and their cardiovascular health benefit documented. For women such programs are scarce.In this report, The feasibility of a cognitive method that was recently demonstrated to prolong lives of women is tested. A setting with gender segregated groups was applied. METHOD: The principles of a behavioural health educational program originally designed to attenuate the stress of patients with coronary prone behaviours were used as a basis for the intervention method. For the groups of female patients this method was tailored according to female stressors and for the groups of men according to male stressors. The same core stress reduction program was used for women and men, but the contents of discussions and responses to the pre planned program varied. These were continuously monitored throughout the fifteen sessions. Implementation group: Thirty consecutive patients, eleven women and nineteen men, hospitalized for an acute coronary syndrome were included in this intervention. All expressed their need to learn how to cope with stress in daily life and were highly motivated. Five groups, three groups of men and two groups of women were formed. Psychological assessments were made immediately before and after completion of the program. RESULTS: No gender differences in the pre planned programs were found, but discussion styles varied between the women and men, Women were more open and more personal. Family issues were more frequent than job issues, although all women were employed outside their homes. Men talked about concrete and practical things, mostly about their jobs, and not directly about their feelings. Daily stresses of life decreased significantly for both men and women, but more so for women. Depressive thoughts were low at baseline, and there was no change over time. In contrast, anxiety scores were high at baseline and decreased significantly, but more so for women than for men. CONCLUSION: Women are likely to benefit from women's groups. Men may prefer to have one or two women in the group, but women fare better in gender segregated groups.

Treating anxiety in patients with coronary heart disease: a randomized controlled trial.

BACKGROUND: Anxiety is frequent in patients with coronary heart disease (CHD) and influences the course of the disease, but no randomized controlled trial has investigated the effects of a psychotherapy intervention in CHD patients with elevated anxiety scores. The main aim of this study was to evaluate the effects of a 6-month psychotherapy intervention on anxiety in this group of patients. METHODS: Fifty-two patients (61 ± 8.0 years, 14 female) with CHD and elevated levels of anxiety completed the study after randomization into a 6-month psychotherapy intervention or a control condition. Medically eligible patients were screened for anxiety with the Hospital Anxiety and Depression Scale (HADS) and were included if they had a score of 8 or higher. Anxiety scores were reevaluated at 6-month follow-up (after the treatment). RESULTS: At 6-month follow-up significant reductions (intervention group: -2.0 ± 2.3; control group: -1.8 ± 2.8; p < 0.01) were found in both groups in the HADS anxiety scale but no significant differences between the groups were observed. Adjustment for baseline differences and disease severity did not change these results. CONCLUSIONS: Our study showed that elevated anxiety scores were reduced over time but there was no statistically significant effect of the psychotherapy intervention in anxious patients with CHD. Changes in the design of the intervention and study might be useful to further investigate this topic in the future.

Waist circumference moderates the association between marital stress and C-reactive protein in middle-aged healthy women.

The relationships among stress, obesity, and inflammation in women remain unclear. This study examined the relationships among marital stress, waist circumference, and C-reactive protein (CRP) in 201 healthy women from the Stockholm Female Coronary Risk Study. We tested whether marital stress was associated with CRP and whether this association was moderated by waist circumference. Hierarchical multiple regression revealed that after adjusting for age, occupation status, fasting glucose, apolipoprotein A1, apolipoprotein B, blood pressure, smoking, and menopausal status, marital stress was not directly associated with CRP. However, waist circumference significantly moderated the association between marital stress and CRP (p = 0.012) such that marital stress was significantly associated with higher CRP among women with larger waist circumferences but not in those with smaller waists. More obese women may be particularly vulnerable to the effects of marital stress by manifesting higher inflammation.

Depressive symptoms and heart rate variability in younger women after an acute coronary event.

OBJECTIVES: We investigated associations between depressive symptoms and reduced heart rate variability (HRV) in women aged 30-65 years after an acute coronary event. BACKGROUND: Younger women have an increased mortality after myocardial infarction compared with men of similar age. Depression was hypothesized to contribute to the poor prognosis, possibly mediated by increased susceptibility to arrhythmias. METHODS: The Stockholm Female Coronary Risk study comprised of 292 women aged 30-65 years who were consecutively admitted for myocardial infarction or unstable angina pectoris during a 3-year period. Depressive symptoms were assessed by means of a 9-item questionnaire. Women with no or only one depressive symptom were classified as low-depression individuals, those with two or more depressive symptoms as high-depression individuals. HRV data were calculated from 24-h ambulatory electrocardiographic recordings 3-6 months after the initial event. RESULTS: Reliable HRV data were obtained from 266 patients. Seventy women were low-depression individuals, and 196 women were high-depression individuals. In univariate analyses, the index of standard deviations of R-R intervals, very low-frequency power, low-frequency power and high-frequency power of HRV were lower in the high-depression individuals. After controlling for potential confounders (diabetes, hypertension, systolic blood pressure, body mass index and ß-blocker medication), a significant difference between low and high-depression individuals was maintained for all indices except for high-frequency power. CONCLUSION: The presence of two or more depressive symptoms was associated with reduced HRV in a high-risk group of younger women after an acute coronary event.

Stress reduction prolongs life in women with coronary disease: the Stockholm Women's Intervention Trial for Coronary Heart Disease (SWITCHD).

BACKGROUND: Psychosocial stress may increase risk and worsen prognosis of coronary heart disease in women. Interventions that counteract women's psychosocial stress have not previously been presented. This study implemented a stress reduction program for women and investigated its ability to improve survival in women coronary patients. METHODS AND RESULTS: Two hundred thirty-seven consecutive women patients, aged 75 years or younger, hospitalized for acute myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention were randomized to a group-based psychosocial intervention program or usual care. Initiated 4 months after hospitalization, intervention groups of 4 to 8 women met for a total of 20 sessions that were spread over a year. We provided education about risk factors, relaxation training techniques, methods for self-monitoring and cognitive restructuring, with an emphasis on coping with stress exposure from family and work, and self-care and compliance with clinical advice. From randomization until end of follow-up (mean duration, 7.1 years), 25 women (20%) in the usual care and 8 women (7%) in the stress reduction died, yielding an almost 3-fold protective effect of the intervention (odds ratio, 0.33; 95% CI, 0.15 to 0.74; P=0.007). Introducing baseline measures of clinical prognostic factors, including use of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, calcium-channel blockers, and statins into multivariate models confirmed the unadjusted results (P=0.009). CONCLUSIONS: Although mechanisms remain unclear, a group-based psychosocial intervention program for women with coronary heart disease may prolong lives independent of other prognostic factors.

[Symptoms of depression and anxiety in patients with coronary heart disease: natural course and results of a psychotherapeutic pilot study]. / Depressivität und Angstlichkeit bei Patienten mit koronarer Herzerkrankung: Spontanverlauf und Ergebnisse einer psychotherapeutischen Pilotstudie.

OBJECTIVES: In this pilot study we examined the natural course of depressive and anxiety symptoms in patients with coronary heart disease over a period of 1(1/2) years. Additionally, we examined patients' interest in participation in a group-psychotherapy. The intervention and its effects on symptom reduction were tested in a subgroup of patients. METHODS: Assessment of anxiety and depression (HADS) in 58 cardiology inpatients at 3 time points (t1 after one year, t2 after 1(1/2) years). N = 9 patients were additionally included in a 6-month psychotherapy intervention and compared to N = 14 untreated patients. RESULTS: 79 % of the patients were interested in beginning a psychotherapy intervention. Without psychotherapeutic treatment, the average psychological strain remained stable over the time of investigation. Intervention-group patients, however, achieved a significant (60 %) reduction in depression and anxiety scores. Implications for the clinical practice and further investigations are discussed.

Autonomic function and prothrombotic activity in women after an acute coronary event.

BACKGROUND: The link between decreased heart rate variability (HRV) and atherosclerosis progression is elusive. We hypothesized that reduced HRV relates to increased levels of prothrombotic factors previously shown to predict coronary risk. METHODS: We studied 257 women (aged 56 +/- 7 years) between 3 and 6 months after an acute coronary event and obtained very low frequency (VLF), low frequency (LF), and high frequency (HF) power, and LF/HF ratio from 24-hour ambulatory ECG recordings. Plasma levels of activated clotting factor VII (FVIIa), fibrinogen, von Willebrand factor antigen (VWF:Ag), and plasminogen activator inhibitor-1 (PAI-1) activity were determined, and their levels were aggregated into a standardized composite index of prothrombotic activity. RESULTS: In bivariate analyses, all HRV indices were inversely correlated with the prothrombotic index explaining between 6% and 14% of the variance (p < 0.001). After controlling for sociodemographic factors, index event, menopausal status, cardiac medication, lifestyle factors, self-rated health, metabolic variables, and heart rate, VLF power, LF power, and HF power explained 2%, 5%, and 3%, respectively, of the variance in the prothrombotic index (p < 0.012). There were also independent relationships between VLF power and PAI-1 activity, between LF power and fibrinogen, VWF:Ag, and PAI-1 activity, between HF power and FVIIa and fibrinogen, and between the LF/HF power ratio and PAI-1 activity, explaining between 2% and 3% of the respective variances (p < 0.05). CONCLUSIONS: Decreased HRV was associated with prothrombotic changes partially independent of covariates. Alteration in autonomic function might contribute to prothrombotic activity in women with coronary artery disease (CAD).

Relation of morning serum cortisol to prothrombotic activity in women with stable coronary artery disease.

BACKGROUND: Increased circulating cortisol levels have been associated with severity of atherosclerosis. Low-grade systemic thrombogenicity plays a major role in the initiation and progression of coronary disease. We hypothesized a direct relationship between cortisol and hemostasis factors related to a prothrombotic state in coronary artery disease. METHODS: We measured morning serum cortisol and activated clotting factor VII, fibrinogen, von Willebrand factor antigen, and plasminogen activator inhibitor-1 activity in 285 women (56 +/- 7 years) between 3 and 6 months after an acute coronary event. To test whether the relationship between cortisol and hemostasis factors would be independent, statistical adjustment was made for demographic, biomedical, life style, and psychosocial variables. RESULTS: Higher serum cortisol levels predicted higher fibrinogen (beta = .17, P = .001) and higher von Willebrand factor (beta = .16, P = .008), all independently of covariates, including C-reactive protein, which was also an independent predictor of fibrinogen (beta = .20, P = .001) and von Willebrand factor (beta = .16, P = .004). Higher levels of vital exhaustion were associated with higher levels of activated clotting factor VII independently of covariates and depression (beta = .18, P = .045). Cortisol showed crude correlations with vital exhaustion (r = .14, P = .022) and with depression (r = .13, P = .043) but did not mediate the relationship between psychosocial variables and hemostatic factors. CONCLUSIONS: Morning serum cortisol showed a modest but independent association with prothrombotic activity in women with coronary artery disease suggesting that increased cortisol levels might contribute to atherosclerosis via eliciting a hypercoagulable state.