Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

OBJECTIVES Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. METHODS We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. RESULTS Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=-0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=-0.05, p<0.05) and arousal (b=-0.09, p<0.05), but not with dissociation and avoidance. CONCLUSIONS The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support.

Association of Trait Resilience With Peritraumatic and Posttraumatic Stress in Patients With Myocardial Infarction.

OBJECTIVE Acute myocardial infarction (MI) is a life-threatening condition, leading to immediate fear and distress in many patients. Approximately 18% of patients develop posttraumatic stress disorder in the aftermath of MI. Trait resilience has shown to be a protective factor for the development of posttraumatic stress disorder. However, whether this buffering effect has already an impact on peritraumatic distress and applies to patients with MI is elusive. METHODS We investigated 98 consecutive patients with acute MI within 48 hours after having reached stable circulatory conditions and 3 months thereafter. Peritraumatic distress was assessed retrospectively with three single-item questions about pain, fear, and helplessness during MI. All patients completed the Posttraumatic Diagnostic Scale (PDS) and the Resilience Scale to self-rate posttraumatic stress and trait resilience. RESULTS Multivariate models adjusting for sociodemographic and medical factors showed that trait resilience was not associated with peritraumatic distress, but significantly so with posttraumatic stress. Patients with greater trait resilience showed lower PDS scores (b = -0.06, p < .001). There was no significant relationship between peritraumatic distress scores and PDS scores; resilience did not emerge as a moderator of this relationship. CONCLUSIONS The findings suggest that trait resilience does not buffer the perception of acute MI as stressful per se but may enhance better coping with the traumatic experience in the longer term, thus preventing the development of MI-associated posttraumatic stress. Trait resilience may play an important role in posttraumatic stress symptoms triggered by medical diseases such as acute MI.

Perception of a hectic hospital environment at admission relates to acute stress disorder symptoms in myocardial infarction patients.

OBJECTIVE Hospital crowding is a public health problem that may impact on the quality of medical treatment and increase the risk of developing traumatic stress, e.g., after myocardial infarction (MI). This study examines whether subjective appraisal of crowding at hospital admission due to MI is associated with acute stress disorder (ASD) symptoms. METHOD We investigated 102 consecutive patients with acute MI within 48h after having reached stable circulatory conditions. The appraisal of crowding was measured by the retrospective assessment of the perception of a hectic hospital environment at admission. Furthermore, patients completed the Acute Stress Disorder Scale to rate the psychological stress reaction. RESULTS The perception of a hectic hospital environment was associated with the development of ASD symptoms (r=0.254, P=.013) independently of demographic, peritraumatic and medical factors. Post hoc analysis revealed associations with dissociative (r=0.211, P=.041), reexperiencing (r=0.184, P=.074) and arousal (r=0.179, P=.083) symptoms. CONCLUSION The findings suggest that, besides objective circumstances, the way hospital admission due to MI is perceived by the patient may influence the development of MI-triggered ASD symptoms. The psychological and physiological long-term outcomes of the perception of a hectic hospital environment and the role of preventive interventions need further examination.

Incremental value of heart-type fatty acid-binding protein in suspected acute myocardial infarction early after symptom onset.

BACKGROUND The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy.

OBJECTIVES Levels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. METHODS The IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. RESULTS At follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (-0.99%, 95% CI -1.84 to -0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). CONCLUSIONS In STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS-defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

Decreased phosphatidylcholine plasmalogens - A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction.

OBJECTIVE Glycerophospholipids and sphingolipids are structurally heterogeneous due to differences in the O- and N-linked fatty acids and head groups. Sphingolipids also show a heterogeneity in their sphingoid base composition which up to now has been little appreciated. The aim of this study was to investigate the association of certain glycerophospholipid and sphingolipid species with stable coronary artery disease (CAD) and acute myocardial infarction (AMI). METHODS The lipid profile in plasma from patients with stable CAD (n = 18) or AMI (n = 17) was compared to healthy subjects (n = 14). Sixty five glycerophospholipid and sphingolipid species were quantified by LC-MS. The relative distribution of these lipids into lipoprotein fractions was analyzed. RESULTS In the CAD cohort, 45 glycerophospholipid and sphingolipid species were significantly lower compared to healthy controls. In the AMI group, 42 glycerophospholipid and sphingolipid species were reduced. Four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) showed the most significant difference. Out of eleven analyzed sphingoid bases, four were lower in the CAD and six in the AMI group. Sphingosine-1-phosphate (S1P) levels were reduced in the AMI group whereas an atypical C16:1 S1P was lower in both groups. Phosphatidylcholine and sphingomyelin species were exclusively present in lipoprotein particles, whereas lysophosphatidylcholines were mainly found in the lipoprotein-free fraction. The observed differences were not explained by the use of statins as confirmed in a second, independent cohort. CONCLUSIONS Reduced levels of four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) were identified as a putatively novel lipid signature for CAD and AMI.

Cryoinjury as a myocardial infarction model for the study of cardiac regeneration in the zebrafish.

The zebrafish heart has the capacity to regenerate after ventricular resection. Although this regeneration model has proved useful for the elucidation of certain regeneration mechanisms, it is based on the removal of heart tissue rather than on tissue damage. We recently characterized the cellular response and regenerative capacity of the zebrafish heart after cryoinjury (CI), an alternative procedure that more closely models the pathophysiological process undergone by the human heart after myocardial infarction (MI). After anesthesia, localized CI with a liquid nitrogen-cooled copper probe induced damage in 25% of the ventricle, in a procedure requiring <5 min. Here we present a detailed description of the technique, which provides a valuable system for the study of the mechanisms of heart regeneration and scar removal after MI in a versatile vertebrate model.

Revascularization Treatment of Emergency Patients with Acute ST-Segment Elevation Myocardial Infarction in Switzerland: Results from a Nationwide, Cross-Sectional Study in Switzerland for 2010-2011

BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide and in Switzerland. When applied, treatment guidelines for patients with acute ST-segment elevation myocardial infarction (STEMI) improve the clinical outcome and should eliminate treatment differences by sex and age for patients whose clinical situations are identical. In Switzerland, the rate at which STEMI patients receive revascularization may vary by patient and hospital characteristics. AIMS: To examine all hospitalizations in Switzerland from 2010-2011 to determine if patient or hospital characteristics affected the rate of revascularization (receiving either a percutaneous coronary intervention or a coronary artery bypass grafting) in acute STEMI patients. DATA AND METHODS: We used national data sets on hospital stays, and on hospital infrastructure and operating characteristics, for the years 2010 and 2011, to identify all emergency patients admitted with the main diagnosis of acute STEMI. We then calculated the proportion of patients who were treated with revascularization. We used multivariable multilevel Poisson regression to determine if receipt of revascularization varied by patient and hospital characteristics. RESULTS: Of the 9,696 cases we identified, 71.6% received revascularization. Patients were less likely to receive revascularization if they were female, and 80 years or older. In the multivariable multilevel Poisson regression analysis, there was a trend for small-volume hospitals performing fewer revascularizations but this was not statistically significant while being female (Relative Proportion = 0.91, 95% CI: 0.86 to 0.97) and being older than 80 years was still associated with less frequent revascularization. CONCLUSION: Female and older patients were less likely to receive revascularization. Further research needs to clarify whether this reflects differential application of treatment guidelines or limitations in this kind of routine data.

Hyperoxia Exacerbates Myocardial Ischemia in the Presence of Acute Coronary Artery Stenosis in Swine.

BACKGROUND Current guidelines limit the use of high oxygen tension after return of spontaneous circulation after cardiac arrest, focusing on neurological outcome and mortality. Little is known about the impact of hyperoxia on the ischemic heart. Oxygen is frequently administered and is generally expected to be beneficial. This study seeks to assess the effects of hyperoxia on myocardia oxygenation in the presence of severe coronary artery stenosis in swine. METHODS AND RESULTS In 22 healthy pigs, we surgically attached a magnetic resonance compatible flow probe to the left anterior descending coronary artery (LAD). In 11 pigs, a hydraulic occluder was inflated distal to the flow probe. After increasing PaO2 to >300 mm Hg, LAD flow decreased in all animals. In 8 stenosed animals with a mean fractional flow reserve of 0.64±0.02, hyperoxia resulted in a significant decrease of myocardial signal intensity in oxygenation-sensitive cardiovascular magnetic resonance images of the midapical segments of the LAD territory. This was not seen in remote myocardium or in the other 8 healthy animals. The decreased signal intensity was accompanied by a decrease in circumferential strain in the same segments. Furthermore, ejection fraction, cardiac output, and oxygen extraction ratio declined in these animals. Changing PaCO2 levels did not have a significant effect on any of the parameters; however, hypercapnia seemed to nonsignificantly attenuate the hyperoxia-induced changes. CONCLUSIONS Ventilation-induced hyperoxia may decrease myocardial oxygenation and lead to ischemia in myocardium subject to severe coronary artery stenosis.

Collagen I modulates growth and gene expression in prostate cancer cells

Prostate cancer is the second leading cause of male cancer-related deaths in the United States. Interestingly, prostate cancer preferentially metastasizes to skeletal tissue. Once in the bone microenvironment, advanced prostate cancer becomes highly resistant to therapeutic modalities. Several factors, such as extracellular matrix (ECM) components, have been implicated in the spread and propagation of prostatic carcinoma. In these studies, we have utilized the PC3 cell line, derived from a human bone metastasis, to investigate the influence of the predominant bone ECM protein, type I collagen, on prostate cancer cell proliferation and gene expression. We have also initiated the design and production of ribozymes to specific gene targets that may influence prostate cancer bone metastasis. ^ Our results demonstrate that PC3 cells rapidly adhere and spread on collagen I to a greater degree than on fibronectin (FN) or poly-L-lysine (PLL). Flow cytometry analysis reveals the presence of the α1, α2 and α3 collagen binding integrin subunits. The use of antibody function blocking studies reveals that PC3 cells can utilize α2β 1 and α3β1 integrins to adhere to collagen I. Once plated on collagen I, the cells exhibit increased rates of proliferation compared with cells plated on FN or tissue culture plastic. Additionally, cells plated on collagen I show increased expression of proteins associated with progression through G1 phase of the cell cycle. Inhibitor studies point to a role for phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and p70 S6 kinase in collagen I-mediated PC3 cell proliferation and cyclin D1 expression. To further characterize the effect of type I collagen on prostate cancer bone metastasis, we utilized a cDNA microarray strategy to monitor type I collagen-mediated changes in gene expression. Results of this analysis revealed a gene expression profile reflecting the increased proliferation occurring on type I collagen. Microarray analysis also revealed differences in the expression of specific gene targets that may impact on prostate cancer metastasis to bone. ^ As a result of our studies on the interaction of prostate cancer cells and the skeletal ECM, we sought to develop novel molecular tools for future gene therapy of functional knockdown experiments. To this end, we developed a series of ribozymes directed against the α2 integrin and at osteopontin, a protein implicated in the metastasis of various cancers, including prostate. These ribozymes should facilitate the future study of the mechanism of prostate cancer cell proliferation, and disease progression occurring at sites of skeletal metastasis where a type I collagen-based environment predominates. ^ Together these studies demonstrate the involvement of bone ECM proteins on prostate cancer cell proliferation and suggest that they may play a significant role on the growth of prostate metastases once in the bone microenvironment. ^

Role of stress myocardial perfusion scan in pre-operative evaluation of cancer patients undergoing non-cardiac surgery

Background. Cardiac risk assessment in cancer patients has not extensively been studied. We evaluated the role of stress myocardial perfusion imaging (MPI) in predicting cardiovascular outcomes in cancer patients undergoing non-cardiac surgery. ^ Methods. A retrospective chart review was performed on 507 patients who had a MPI from 01/2002 - 03/2003 and underwent non-cardiac surgery. Median follow-up duration was 1.5 years. Cox proportional hazard model was used to determine the time-to-first event. End points included total cardiac events (cardiac death, myocardial infarction (MI) and coronary revascularization), cardiac death, and all cause mortality. ^ Results. Of all 507 MPI studies 146 (29%) were abnormal. There were significant differences in risk factors between normal and abnormal MPI groups. Mean age was 66±11 years, with 60% males and a median follow-up duration of 1.8 years (25th quartile=0.8 years, 75th quartile=2.2 years). The majority of patients had an adenosine stress study (53%), with fewer exercise (28%) and dobutamine stress (16%) studies. In the total group there were 39 total cardiac events, 31 cardiac deaths, and 223 all cause mortality events during the study. Univariate predictors of total cardiac events included CAD (p=0.005), previous MI (p=0.005), use of beta blockers (p=0.002), and not receiving chemotherapy (p=0.012). Similarly, the univariate predictors of cardiac death included previous MI (p=0.019) and use of beta blockers (p=0.003). In the multivariate model for total cardiac events, age at surgery (HR 1.04, p=0.030), use of beta blockers (HR 2.46; p=0.011), dobutamine MPI (HR 3.08; p=0.018) and low EF (HR 0.97; p=0.02) were significant predictors of worse outcomes. In the multivariate model for predictors of cardiac death, beta blocker use (HR=2.74; p=0.017) and low EF (HR=0.95; p<0.003) were predictors of cardiac death. The only univariate MPI predictor of total cardiac events was scar severity (p=0.005). While MPI predictors of cardiac death were scar severity (p= 0.001) and ischemia severity (p=0.02). ^ Conclusions. Stress MPI is a useful tool in predicting long term outcomes in cancer patients undergoing surgery. Ejection fraction and severity of myocardial scar are important factors determining long term outcomes in this group.^