Role of Heart Rate Variability in the Association between Myocardial Infarction Severity and Post-Myocardial Infarction Distress.

OBJECTIVE: Myocardial infarction (MI) results in mental health consequences, including depression and post-traumatic stress disorder (PTSD). The risk and protective factors of such mental consequences are not fully understood. This study examined the relation between MI severity and future mental health consequences and the moderating role of vagal nerve activity. METHODS: In a reanalysis of data from the Myocardial Infarction-Stress Prevention Intervention (MI-SPRINT) study, 154 post-MI patients participated. MI severity was measured by the Killip Scale and by troponin levels. Depression and PTSD symptoms were assessed with valid questionnaires, both at 3 and 12 months. Vagal nerve activity was indexed by the heart rate variability (HRV) parameter of the root-mean square of successive R-R differences (RMSSD). Following multivariate analyses, the association between MI severity and distress was examined in patients with low and high HRV (RMSSD = 30 ms). RESULTS: In the full sample, the Killip index predicted post-MI distress only at 3 months, while troponin predicted distress at 3- and 12-months post-MI. However, HRV moderated the effects of the Killip classification; Killip significantly predicted symptoms of depression and PTSD at 3- and 12-months post-MI, but only in patients with low HRV. Such moderation was absent for troponin. CONCLUSION: MI severity (Killip classification) predicted post-MI depression and PTSD symptoms, but only in patients with low HRV, suggesting that the vagal nerve is a partial protective (moderating) factor in the relation between Killip score and post-MI distress.

Association of positive psychological well-being with circulating inflammatory markers: A systematic review and meta-analysis.

Accumulating evidence shows a protective effect of positive psychological well-being (PPWB) on health outcomes. However, the underlying mechanisms remain poorly understood. One pathway relates to enhanced immune functioning (Boehm, 2021). The aim of this project was to conduct a systematic review and meta-analysis of the association between PPWB and circulating inflammatory biomarkers and determine the magnitude of this association. After examining 748 references, 29 studies were included. Results from over 94'700 participants revealed a significant association between PPWB and reduced levels of interleukin (IL)- 6 (r = -0.05; P < .001) and C-reactive protein (CRP) (r = -0.06; P < .001) with a heterogeneity of I2 = 31.5% and I2 = 84.5%, respectively. Only the association of PPWB with CRP was independent of co-variates included in the individual studies (r = -0.04; P = .027). The findings of this systematic review and meta-analysis suggest that PPWB is associated with lower levels of inflammatory biomarkers IL-6 and CRP in the circulation. Such relationships with inflammatory biomarkers may partly explain positive effects of PPWB on health.

Reply to Sopek Merkas, I.; Lakusic, N. Comment on "von Känel et al. Early Trauma-Focused Counseling for the Prevention of Acute Coronary Syndrome-Induced Posttraumatic Stress: Social and Health Care Resources Matter. J. Clin. Med. 2022, 11, 1993".

We thank Merkas and Lakusic for commenting on our recently published paper; in the paper, we suggested that resources in a patient's social environment may moderate the benefit of one single-session trauma-focused counseling in the prevention of acute coronary syndrome (ACS)-induced posttraumatic stress disorder (PTSD) symptoms [...].

Sleep disturbance after acute coronary syndrome: A longitudinal study over 12 months.

BACKGROUND: Sleep disturbance has been associated with poor prognosis in patients with acute coronary syndrome (ACS). This study examined the course of sleep disturbance and associated factors in patients with ACS who were followed for one year. METHODS: Study participants were 180 patients (mean age 59.6 years, 81.7% men) with ACS admitted to a tertiary hospital to undergo acute coronary intervention. Sleep disturbance was interviewer-assessed at admission (n = 180), at 3 months (n = 146), and at 12 months (n = 101) using the Jenkins Sleep Scale (JSS)-4, with a total of 414 assessments over one year. Random linear mixed regression models were used to evaluate the relationship between sociodemographic factors, cardiac diseases severity, perceived distress during ACS, comorbidities, medication, health behaviors, and sleep disturbance over time. RESULTS: At admission, 3 months, and 12 months, 56.7%, 49.3%, and 49.5% of patients, respectively, scored above the mean value for sleep disturbance in the general population (JSS-4 score ≥5). There was a significant decrease in continuous JSS-4 scores over time [estimate (SE) = -0.211 (0.074), p = 0.005]. Female sex [0.526 (0.206), p = 0.012], greater fear of dying [0.074 (0.026), p = 0.004], helplessness during ACS [0.062 (0.029), p = 0.034], and a history of depression [0.422 (0.171), p = 0.015] were independently associated with higher JSS-4 scores over time. CONCLUSION: Despite a decrease from admission to 3 months, sleep disturbance is prevalent in the first year after ACS. Female sex, depression history, and distress during ACS identify patients at increased risk of developing persistent sleep disturbance and may inform interventions to prevent sleep disturbance.

Relationship between a Self-Reported History of Depression and Persistent Elevation in C-Reactive Protein after Myocardial Infarction.

Background: Elevated levels of C-reactive protein (CRP) are associated with both an increased risk of cardiovascular disease (CVD) and depression. We aimed to test the hypothesis that a self-report history of depression is associated with a smaller decrease in CRP levels from hospital admission to 3-month follow-up in patients with acute myocardial infarction (MI). Methods: We assessed 183 patients (median age 59 years; 84% men) with verified MI for a self-report history of lifetime depression and plasma CRP levels within 48 h of an acute coronary intervention and again for CRP levels at three months. CRP values were categorized according to their potential to predict CVD risk at hospital admission (acute inflammatory response: 0 to <5 mg/L, 5 to <10 mg/L, 10 to <20 mg/L, and ≥20 mg/L) and at 3 months (low-grade inflammation: 0 to <1 mg/L, 1 to <3 mg/L, and ≥3 mg/L). Additionally, in a subsample of 84 patients showing admission CRP levels below 20 mg/L, changes in continuous CRP values over time were also analyzed. Results: After adjustment for a range of potentially important covariates, depression history showed a significant association with a smaller decrease in both CRP risk categories (r = 0.261, p < 0.001) and log CRP levels (r = 0.340, p = 0.005) over time. Conclusions: Self-reported history of depression may be associated with persistently elevated systemic inflammation three months after MI. This finding warrants studies to test whether lowering of inflammation in patients with an acute MI and a history of depression may improve prognosis.

Association Between Changes in Post-hospital Cardiac Symptoms and Changes in Acute Coronary Syndrome-Induced Symptoms of Post-traumatic Stress.

Background: After acute coronary syndrome (ACS), one in eight patients develops clinically significant symptoms of Post-traumatic stress disorder (PTSD). We hypothesized that changes in cardiac symptoms from 3 to 12 months after ACS are associated with changes in ACS-induced PTSD symptoms. Methods: At 3 (n = 154) and/or 12 months (n = 106) post-ACS, patients (n = 156, mean age 59 years, 85% men) completed a clinical interview assessing chest tightness/pain (at rest and/or during exertion), heartbeat symptoms (heart palpitations, racing of heart, heart stumbling or skipping a beat) and PTSD symptoms during the prior 4 weeks. Random mixed regression models examined the association between the onset (or remission) from 3 to 12 months in cardiac symptoms with changes in PTSD symptoms, adjusting for a range of potential predictors of ACS-induced PTSD symptoms. Results: The onset of chest tightness/pain [estimate = 0.588, 95% confidence interval: 0.275, 0.090; p < 0.001] and of heartbeat symptoms [0.548 (0.165, 0.931); p = 0.005] from 3 to 12 months was independently associated with an increase in total PTSD symptoms. There were also independent associations between the onset of chest tightness/pain and heartbeat symptoms with an increase in PTSD symptom clusters. Specifically, the onset of chest tightness/pain showed associations with an increase in re-experiencing [0.450 (0.167, 0.733); p = 0.027] and avoidance/numbing [0.287 (0.001, 0.574); p = 0.049]. The onset of heartbeat symptoms showed associations with an increase in re-experiencing [0.392 (0.045, 0.739); p = 0.002], avoidance/numbing [0.513 (0.161, 0.864); p = 0.004] and hyperarousal [0.355 (0.051, 0.659); p = 0.022]. An increase in the total number of cardiac symptoms (score range 0-6) was also associated with an increase in total PTSD symptoms [0.343 (0.202, 0.484); p < 0.001]. Psychotherapy in the post-hospital period moderated the association between the change in heartbeat symptoms and the change in total PTSD symptoms [-0.813 (-1.553, -0.074); p = 0.031 for interaction]; the association between the onset of heart beat symptoms and an increase in total PTSD symptoms was weaker in patients who attended psychotherapy [0.437 (-0.178, 1.052); p = 0.16] than in those who did not [0.825 (0.341, 1.309); p < 0.001]. Conclusion: Changes in cardiac symptoms between 3 and 12 months after hospitalization are associated with changes in ACS-induced PTSD symptoms. ClinicalTrials.gov #NCT01781247.

Early Trauma-Focused Counseling for the Prevention of Acute Coronary Syndrome-Induced Posttraumatic Stress: Social and Health Care Resources Matter.

BACKGROUND: A one-size-fits-all approach might explain why early psychological interventions are largely ineffective in preventing the development of posttraumatic stress disorder (PTSD) symptoms triggered by acute medical events. We examined the hypothesis that social and health care resources are moderators of an intervention effect. METHODS: Within 48 h of hospital admission, 129 patients (mean age 58 years, 83% men) with acute coronary syndrome (ACS) self-rated their social support and were randomized to one single session of trauma-focused counseling (TFC) or stress-focused counseling (SFC) (active control intervention). Clinician-rated PTSD symptoms, use of cardiac rehabilitation (CR) and use of psychotherapy were assessed at 3 and 12 months. Random mixed regression multivariable models were used to analyze associations with PTSD symptoms over time. RESULTS: TFC did not prevent ACS-induced PTSD symptom onset better than SFC; yet, there were significant and independent interactions between "intervention" (TFC or SFC) and social support (p = 0.013) and between "intervention" and duration of CR in weeks (p = 0.034). Patients with greater social support or longer participation in CR had fewer PTSD symptoms in the TFC group compared with the SFC group. The number of psychotherapy sessions did not moderate the intervention effect. CONCLUSIONS: Early psychological intervention after ACS with a trauma-focused approach to prevent the development of PTSD symptoms may be beneficial for patients who perceive high social support or participate in CR for several weeks.

Prospective association between pro-inflammatory state on admission and posttraumatic stress following acute coronary syndrome.

OBJECTIVE: The traumatic experience of acute coronary syndrome (ACS) may induce symptoms of posttraumatic stress disorder (PTSD). We examined whether the ACS-triggered acute inflammatory response predicts the development of PTSD symptoms. METHOD: Study participants were 70 patients (all Caucasian, 80% male, mean age 59 years) with myocardial infarction (MI) during the acute treatment phase. Interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-4, IL-10, and transforming growth factor (TGF)-1ß were determined in plasma collected within 48 h of hospital admission. Participants self-assessed the severity of ACS-induced PTSD symptoms with the 17-item Posttraumatic Diagnostic Scale at 12 months. RESULTS: There was a significant positive association of the pro-inflammatory index (added standardized z-scores of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α) with total PTSD symptom severity (ΔR2 = 0.050, p = .029) and re-experiencing symptoms (ΔR2 = 0.088, p = .008), but not avoidance/numbing and hyperarousal symptoms. Analyses were adjusted for the anti-inflammatory index (added standardized z-scores of IL-4, IL-10, and TGF-ß1), trauma-focused counseling, sex, age, time since pain onset, troponin, body mass index, and distress during MI. Results were robust when the anti-inflammatory index was removed from the model. Additional analyses showed significant associations of both the net-inflammatory index (i.e., pro-inflammatory index minus anti-inflammatory index) and IL-1ß with total PTSD symptom severity, re-experiencing, and hyperarousal symptoms (ΔR2 between 0.042 and 0.090) and of IL-1ß with avoidance/numbing symptoms (ΔR2 = 0.050). CONCLUSIONS: The findings suggest an association between the pro-inflammatory state launched during ACS and the development of PTSD symptoms. Increased IL-1ß may play a particular role in the pathophysiology of ACS-induced PTSD symptoms.

Longitudinal association between cognitive depressive symptoms and D-dimer levels in patients following acute myocardial infarction.

BACKGROUND: A prothrombotic tendency could partially explain the poor prognosis of patients with coronary heart disease and depression. We hypothesized that cognitive depressive symptoms are positively associated with the coagulation activation marker D-dimer throughout the first year after myocardial infarction (MI). METHODS: Patients with acute MI (mean age 60 years, 85% men) were investigated at hospital admission (n = 190), 3 months (n = 154) and 12 months (n = 106). Random linear mixed regression models were used to evaluate the relation between cognitive depressive symptoms, assessed with the Beck depression inventory (BDI), and changes in plasma D-dimer levels. Demographics, cardiac disease severity, medical comorbidity, depression history, medication, health behaviors, and stress hormones were considered for analyses. RESULTS: The prevalence of clinical depressive symptoms (13-item BDI score ≥ 6) was 13.2% at admission and stable across time. Both continuous (p < .05) and categorical (p < .010) cognitive depressive symptoms were related to higher D-dimer levels over time, independent of covariates. Indicating clinical relevance, D-dimer was 73 ng/ml higher in patients with a BDI score ≥ 6 versus those with a score < 6. There was a cognitive depressive symptom-by-cortisol interaction (p < .05) with a positive association between cognitive depressive symptoms and D-dimer when cortisol levels were high (p < .010), but not when cortisol levels were low (p > .05). Fluctuations (up and down) of cognitive depressive symptoms and D-dimer from one investigation to the next showed also significant associations (p < .05). CONCLUSIONS: Cognitive depressive symptoms were independently associated with hypercoagulability in patients up to 1 year after MI. Hypothalamic-pituitary-adrenal axis could potentially modify this effect.

Serum cortisol as a predictor for posttraumatic stress disorder symptoms in post-myocardial infarction patients.

BACKGROUND: After an acute myocardial infarction (MI2), patients may develop posttraumatic stress disorder (PTSD3). There is evidence for alterations in the hypothalamic-pituitary-adrenal axis in PTSD. An association between patients` cortisol level after experiencing an MI and subsequent PTSD symptoms has not been investigated yet. Therefore, the aim of this study was to examine whether serum cortisol measured in patients admitted to hospital for acute coronary care after MI is predictive of PTSD symptoms at three and 12 months post-MI, respectively. METHODS: Patients (N=106) with a verified MI and high risk for the development of MI-induced PTSD symptoms were included in the study within 48 hours of hospital admission for acute coronary intervention. Serum cortisol was measured from fasting venous blood samples the next morning. Hierarchical regression analysis was used to test for an independent contribution of cortisol levels from admission to the Clinician-Administered PTSD Scale sum score three and 12 months after discharge from the coronary care unit. RESULTS: Hierarchical regression analysis showed that lower serum cortisol levels were significantly associated with more severe PTSD symptoms three months (B=-0.002, p=0.042) and 12 months (B=-0.002, p=0.043) post-MI. LIMITATIONS: The generalizability of the findings is limited to patients with high acute peri-traumatic distress and without an acute severe depressive episode. The study does not provide any information about the diurnal cortisol pattern. CONCLUSION: Lower serum cortisol measured during MI hospitalization may predict more severe MI-induced PTSD symptoms three and 12 months after hospital discharge.

Course, Moderators, and Predictors of Acute Coronary Syndrome-Induced Post-traumatic Stress: A Secondary Analysis From the Myocardial Infarction-Stress Prevention Intervention Randomized Controlled Trial.

Acute coronary syndromes (ACS) induce post-traumatic stress symptoms (PTSS) in one out of eight patients. Effects of preventive interventions, the course and potential moderators of ACS-induced PTSS are vastly understudied. This study explored whether a preventive behavioral intervention leads to a decrease in myocardial infarction (MI)-induced PTSS between two follow-up assessments. Sociodemographic, clinical and psychological factors were additionally tested as both moderators of change over time in PTSS and predictors of PTSS across two follow-ups. Within 48 h after reaching stable circulatory conditions, 104 patients with MI were randomized to a 45-min one-session intervention of either trauma-focused counseling or stress counseling (active control). Sociodemographic, clinical, and psychological data were collected at baseline, and PTSS were assessed with the Clinician-Administered Post-traumatic Stress Disorder Scale 3 and 12 months post-MI. PTSS severity showed no change over time from 3 to 12 months post-MI, either in all patients or through the intervention [mean group difference for total PTSS = 1.6 (95% CI -1.8, 4.9), re-experiencing symptoms = 0.8 (95% CI -0.7, 2.2), avoidance/numbing symptoms = 0.1 (95% CI -1.6, 1.7) and hyperarousal symptoms = 0.6 (95% CI -0.9, 2.1)]. Patients receiving one preventive session of trauma-focused counseling showed a decrease from 3 to 12 months post-MI in avoidance symptoms with higher age (p = 0.011) and direct associations of clinical burden indices with total PTSS across both follow-ups (p's ≤ 0.043; interaction effects). Regardless of the intervention, decreases in re-experiencing, avoidance and hyperarousal symptoms from 3 to 12 months post-MI occurred, respectively, in men (p = 0.006), participants with low education (p = 0.014) and with more acute stress symptoms (p = 0.021). Peritraumatic distress (p = 0.004) and lifetime depression (p = 0.038) predicted total PTSS across both follow-ups. We conclude that PTSS were persistent in the first year after MI and not prevented by an early one-session intervention. A preventive one-session intervention of trauma-focused counseling may be inappropriate for certain subgroups of patients, although this observation needs confirmation. As predictors of the development and persistence of PTSS, sociodemographic and psychological factors could help to identify high-risk patients yet at hospital admission.

Insomnia Symptoms and Acute Coronary Syndrome-Induced Posttraumatic Stress Symptoms: A Comprehensive Analysis of Cross-sectional and Prospective Associations.

BACKGROUND: Acute coronary syndrome (ACS) induces clinically significant posttraumatic stress symptoms (PTSS) in 12% of patients. Subjective sleep problems are a risk factor for the development of PTSS, but this is underexplored in patients with ACS. PURPOSE: To examine the association of insomnia symptoms with ACS-induced PTSS. METHODS: In this longitudinal study with 154 patients (all white, 84.4% male, mean age 58.7 years) with a verified ACS, insomnia symptoms were interviewer assessed at hospital admission and at 3 months, using the Jenkins Sleep Scale (JSS)-4. ACS-induced PTSS were assessed with the Clinician-Administered Posttraumatic Stress Disorder Scale 3 months after hospital admission. In multivariable linear models, insomnia symptoms were regressed on PTSS, adjusting for demographics, clinical variables, health behaviors, and psychological data, including cognitive depressive symptoms. RESULTS: Greater insomnia symptoms at admission (ß = .165, p = .034), greater increase in insomnia symptoms from admission to 3 months (ß = .233, p = .008), and greater insomnia symptoms at 3 months (ß = .239, p = .002) were independently associated with more severe total PTSS at 3 months. Concerning the individual PTSS clusters, both insomnia symptoms at admission (ß = .214, p = .007) and at 3 months (ß = .213, p = .012) were independently associated with reeexperiencing symptoms. Removing sleep items from PTSS scores and excluding patients on antidepressants in two sensitivity analyses did not substantially change the results. CONCLUSIONS: Insomnia symptoms could play an important role in the development and severity of ACS-induced PTSS. This relationship seems not simply explained by the fact that sleeping difficulties are inherent to the phenotype of posttraumatic stress disorder. CLINICAL TRIAL INFORMATION: NCT01781247.

Pharmacotherapy in the Management of Anxiety and Pain During Acute Coronary Syndromes and the Risk of Developing Symptoms of Posttraumatic Stress Disorder.

Background Benzodiazepines and morphine are given during acute coronary syndromes (ACSs) to alleviate anxiety and pain, and ß-blockers may also reduce pain. ACS may induce posttraumatic stress disorder (PTSD) symptoms (PTSS). When taken during trauma other than ACS, benzodiazepines increase the risk of PTSS, but it is unknown if benzodiazepines increase the risk of PTSS in ACS. We examined the effects of drug exposure during ACS on the development of PTSS. Methods and Results Study participants were 154 patients with a verified ACS. Baseline demographics, clinical variables, and psychological measures were obtained through a medical history, through a psychometric assessment, and from patient records, and used as covariates in linear regression analysis. Three months after ACS, the severity of PTSS was assessed with the Clinician-Administered PTSD Scale. During ACS, 37.7% of patients were exposed to benzodiazepines, whereas 72.1% were exposed to morphine and 88.3% were exposed to ß-blockers, but only 7.1% were exposed to antidepressants. Eighteen (11.7%) patients developed clinical PTSD. Adjusting for all covariates, benzodiazepine use was significantly associated with the Clinician-Administered PTSD Scale total severity score (unstandardized coefficient B [SE], 0.589 [0.274]; partial r=0.18; P=0.032) and the reexperiencing subscore (B [SE], 0.433 [0.217]; partial r=0.17; P=0.047). Patients exposed to benzodiazepines had an almost 4-fold increased relative risk of developing clinical PTSD, adjusting for acute stress disorder symptoms (odds ratio, 3.75; 95% CI, 1.31-10.77). Morphine, ß-blockers, and antidepressants showed no predictive value. Conclusions Notwithstanding short-term antianxiety effects during ACS, benzodiazepine use might increase the risk of ACS-induced PTSS with clinical significance, thereby compromising patients' quality of life and prognosis. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01781247.

Association of sleep problems with neuroendocrine hormones and coagulation factors in patients with acute myocardial infarction.

BACKGROUND: Obstructive sleep apnea (OSA) and insomnia are frequent sleep problems that are associated with poor prognosis in patients with coronary heart disease. The mechanisms linking poor sleep with an increased cardiovascular risk are incompletely understood. We examined whether a high risk of OSA as well as insomnia symptoms are associated with neuroendocrine hormones and coagulation factors in patients admitted with acute myocardial infarction. METHODS: We assessed 190 patients (mean age 60 years, 83% men) in terms of OSA risk (STOP screening tool for the assessment of high vs. low OSA risk) and severity of insomnia symptoms (Jenkins Sleep Scale for the assessment of subjective sleep difficulties) within 48 h of an acute coronary intervention. Circulating concentrations of epinephrine, norepinephrine, cortisol, fibrinogen, D-dimer, and von Willebrand factor were measured the next morning. The association of OSA risk and insomnia symptoms with neuroendocrine hormones and coagulation factors was computed using multivariate models adjusting for demographic factors, health behaviors, somatic and psychiatric comorbidities, cardiac disease-related variables, and OSA risk in the model for insomnia symptoms, respectively, for insomnia symptoms in the model for OSA risk. RESULTS: High OSA risk was identified in 41% of patients and clinically relevant insomnia symptoms were reported by 27% of patients. Compared to those with low OSA risk, patients with high OSA risk had lower levels of epinephrine (p = 0.015), norepinephrine (p = 0.049) and cortisol (p = 0.001). More severe insomnia symptoms were associated with higher levels of fibrinogen (p = 0.037), driven by difficulties initiating sleep, and with lower levels of norepinephrine (p = 0.024), driven by difficulties maintaining sleep. CONCLUSIONS: In patients with acute myocardial infarction, sleep problems are associated with neuroendocrine hormones and coagulation activity. The pattern of these relationships is not uniform for patients with a high risk of OSA and those with insomnia symptoms, and whether they contribute to adverse cardiovascular outcomes needs to be established. TRIAL REGISTRATION: ClinicalTrials.gov NCT01781247 .

The Role of Illness Perception and Its Association With Posttraumatic Stress at 3 Months Following Acute Myocardial Infarction.

Background: The aim of this study was to investigate the relationship between illness perception and posttraumatic stress disorder (PTSD) symptoms at three months following acute myocardial infarction (MI). Methods: Patients (n = 96) were examined within 48 h and 3 months after the illness episode. The brief revised illness perception questionnaire (Brief-IPQ) was used to assess patients' cognitive representation of their MI. At 3-month follow-up, the Posttraumatic Diagnostic Scale (PDS) and the Clinician-Administered PTSD Scale (CAPS) were used to assess the level of PTSD symptoms. Results: The subjective perception of the illness, including higher harmful consequences (r > 0.35, p < 0.01), higher illness concerns (r > 0.24, p < 0.05) and more emotional impairment (r > 0.23, p < 0.05), was associated with both self-rated and clinician-rated PTSD symptoms. Beliefs regarding harmful consequences after acute MI were independently associated with levels of PTSD symptoms assessed with both the self-rated PDS and CAPS interview (standardized ß coefficient = 0.24; P < 0.05) adjusted for demographic factors, cognitive depressive symptoms, fear of dying during MI, factors related to study design, and illness severity. Conclusions: The findings suggest that initial perception of acute MI is significantly associated with PTSD symptoms attributable to MI at 3 months follow-up.

C-reactive protein as a predictor of posttraumatic stress induced by acute myocardial infarction.

BACKGROUND: Acute coronary syndrome (ACS) may cause clinically relevant posttraumatic stress disorder symptoms (PTSS). An inflammatory state might be one mechanism linking PTSS with poor prognosis after ACS. We tested the hypothesis that a change in C-reactive protein (CRP) between hospital admission and 3-month follow-up is an independent predictor of ACS-triggered PTSS. METHODS: We assessed 183 patients (median age 59 years; 84% men) with verified myocardial infarction (MI) within 48 h of an acute coronary intervention and three months post-MI for self-rated PTSS. 14 (7.7%) patients fulfilled definition criteria for PTSS caseness. CRP values were categorized according to the predicted risk of cardiovascular disease (CVD) at hospital admission (acute inflammatory response): 0 to <5 mg/L, 5 to <10 mg/L, 10 to <20 mg/L, and ≥ 20 mg/L; and at 3-month follow-up (low-grade inflammation): 0 to <1 mg/L, 1 to <3 mg/L, and ≥ 3 mg/L. Additionally, in a subsample of 84 patients with CRP levels below 20 mg/L at admission, CRP values were log-transformed. RESULTS: After adjustment for covariates, less of a reduction or an increase of log CRP values between admission and 3-month follow-up predicted PTSS caseness (OR 6.25, 95% CI 1.25, 31.38), and continuous PTSS (unstandardized B = 0.21, 95% CI 0.07, 4.19; p = 0.043). Less reduction in CRP risk categories predicted both PTSS caseness (OR 4.14, 95% CI 1.89, 9.06) and continuous PTSS (B = 1.80, 95% CI 1.09, 2.51; p < 0.001). CONCLUSIONS: Persistently heightened inflammation seems to be predictive for the development of PTSS three months after ACS, so interventions to lower inflammation might be warranted.

Early Psychological Counseling for the Prevention of Posttraumatic Stress Induced by Acute Coronary Syndrome: The MI-SPRINT Randomized Controlled Trial.

BACKGROUND: Acute coronary syndrome (ACS)-induced posttraumatic stress disorder (PTSD) and clinically significant PTSD symptoms (PTSS) are found in 4 and 12% of patients, respectively. We hypothesized that trauma-focused counseling prevents the incidence of ACS-induced PTSS. METHODS: Within 48 h of hospital admission, 190 patients with high distress during ACS were randomized to a single-session intervention of either trauma-focused counseling or an active control intervention targeting the general role of stress in patients with heart disease. Blind interviewer-rated PTSS (primary outcome) and additional health outcomes were assessed at 3 months of follow-up. Trial results about prevalence were compared with data from previous studies on the natural incidence of ACS-induced PTSS/PTSD. RESULTS: Intention-to-treat analyses revealed no difference in interviewer-rated PTSS between trauma-focused counseling (mean, 11.33; 95% Cl, 9.23-13.43) and stress counseling (9.88; 7.36-12.40; p = 0.40), depressive symptoms (6.01, 4.98-7.03, vs. 4.71, 3.65-5.77; p = 0.08), global psychological distress (5.15, 4.07-6.23, vs. 3.80, 2.60-5.00; p = 0.11), and the risk for cardiovascular-related hospitalization/all-cause mortality (OR, 0.67; 95% CI, 0.37-1.23). Self-rated PTSS indicated less beneficial effects with trauma-focused (6.54; 4.95-8.14) versus stress counseling (3.74; 2.39-5.08; p = 0.017). The completer analysis (154 cases) confirmed these findings. The prevalence rates of interviewer-rated PTSD (0.5%, 1/190) and self-rated PTSS were in this trial much lower than in meta-analyses and observation studies from the same cardiology department. CONCLUSIONS: Benefits were not seen for trauma-focused counseling when compared with an active control intervention. Nonetheless, in distressed ACS patients, individual, single-session, early psychological counseling shows potential as a means to prevent posttraumatic responses, but trauma-focused early treatments should probably be avoided.

Low Self-rated Health Is Related to Blood Hypercoagulability in Patients Admitted with Acute Myocardial Infarction.

Self-rated health (SRH) is independently associated with all-cause mortality and adverse cardiovascular outcomes in individuals with and without cardiovascular disease. We examined whether SRH relates to haemostatic factors of a hypercoagulable state with prognostic impact in patients admitted with acute myocardial infarction (MI). We assessed 190 patients (median age: 59 years; all Caucasian; 83% men) within 48 hours of an acute coronary intervention in terms of demographic factors, medical and psychiatric comorbidity, health behaviours, cardiac-related variables and psychosocial characteristics. Patients rated their health state before MI retrospectively with the EuroQol Visual Analogue Scale ranging from 0 ('worst imaginable health state') to 100 ('best imaginable health state'). Circulating levels of fibrinogen, fibrin D-dimer and von Willebrand factor (VWF) antigen were measured the morning after hospital referral. The median score of SRH was 75 (range: 20-100). SRH was inversely associated with fibrinogen (r = - 0.25, p = 0.001) and D-dimer (r = - 0.17, p = 0.021) levels in the bivariate analysis. Stronger relationships emerged for fibrinogen (r = - 0.33, p < 0.001), D-dimer (r = - 0.25, p = 0.001) and also VWF (r = - 0.19, p = 0.015) levels in fully adjusted linear regression models. As for SRH, the Global Registry of Acute Coronary Events (GRACE) risk score was the only covariate showing an independent association with all haemostatic factors (fibrinogen: r = 0.31, D-dimer: r = 0.29, VWF: r = 0.30; all p-values < 0.001). Lower SRH was associated with greater coagulability in patients with acute MI, independent of covariates and comparable with the GRACE risk score. The findings provide a novel psychobiological mechanism that may potentially link SRH with cardiovascular outcome in patients with an acute coronary syndrome.

Acute stress disorder and C-reactive protein in patients with acute myocardial infarction.

Background Myocardial infarction-triggered acute stress disorder (ASD) and subclinical inflammation associate with the development of posttraumatic stress disorder, and worsen the prognosis of myocardial infarction patients. We examined the relationship between ASD severity and C-reactive protein levels in patients with acute myocardial infarction. Methods We assessed 190 patients (median age 59 years; 83% men) with a verified myocardial infarction within 48 h of an acute coronary intervention. Circulating levels of C-reactive protein were categorized according to their prognostic risk for cardiovascular disease: 0 to <5, 5 to <10, 10 to <20, and ≥ 20 mg/l. Patients completed the ASD-Scale (ASDS) for myocardial infarction-triggered symptoms and questionnaires for demographic factors, health behaviours, cardiac-related variables and psychosocial characteristics. Results The ASDS sum score was positively associated with C-reactive protein categories in the bivariate analysis ( r = 0.20, p < 0.01). Significant relationships with C-reactive protein also emerged for dissociation ( r = 0.25, p < 0.001) and avoidance ( r = 0.19, p < 0.01), but not for arousal and re-experiencing. Similarly, C-reactive protein levels ≥ 20 mg/l versus < 20 mg/l were predicted by the ASDS sum score, and the dissociation, avoidance and arousal subscores (all p-values < 0.05) in the fully adjusted binary regression analyses. C-reactive protein levels ≥ 20 mg/l were also independently predicted by male gender, body mass index, lower education, and lower left ventricular ejection fraction and higher white blood cell count. Conclusions Higher levels of myocardial infarction-triggered ASD symptoms associate with a greater inflammatory response in patients with acute myocardial infarction independently of important covariates. The findings suggest a link between myocardial infarction-triggered ASD symptoms and a heightened acute phase response with a potential impact on cardiovascular disease prognosis.

Are Inflammatory Cytokines Associated with Pain during Acute Myocardial Infarction?

OBJECTIVE: Pain and inflammation during acute myocardial infarction (AMI) have been associated with the development of posttraumatic stress disorder and may also impact negatively on somatic outcome. We investigated the relationship between pain during AMI and levels of circulating proinflammatory (tumor necrosis factor [TNF]-α, interleukin [IL]-6) and anti-inflammatory (IL-33 and tissue growth factor [TGF]-ß1) cytokines. METHODS: Data were collected as part of the Myocardial Infarction - Stress Prevention Intervention (MI-SPRINT) study. We included 140 patients (mean age 59.6 years, 82.1% male) with high acute psychological distress within 48 h after MI. Fasting blood samples were drawn thereafter to measure cytokine levels. Sociodemographic factors, psychological and medical data, as well as cardiometabolic markers were assessed with questionnaires and patient interviews. RESULTS: Linear regression models showed a significant positive correlation of pain with TGF-ß1 (b = 770.91, p = 0.031) and a significant inverse correlation of pain with IL-33 (b = -0.11, p = 0.015) after controlling for age, gender, body mass index, lifetime depression, acute stress disorder symptoms, and the prognostic Global Registry of Acute Coronary Events (GRACE) score. Pain was not associated with IL-6 but with the GRACE score (b = 0.01, p = 0.003). Pain showed no significant association with TNF-α. CONCLUSION: Pain during MI was associated with anti- but not proinflammatory cytokines. As IL-33 has been shown to be cardioprotective, lower IL-33 levels with more intense pain may suggest a pathway through which increased pain during MI may have an impact on the medical prognosis.