α1-Antichymotrypsin Complex (SERPINA3) Is an Independent Predictor of All-Cause but Not Cardiovascular Mortality in Patients Hospitalized for Chest Pain of Suspected Coronary Origin.

INTRODUCTION: SERPINA3 is an acute-phase protein triggered by inflammation. It is upregulated after an acute myocardial infarction (AMI). Data on its long-term prognostic value in MI patients are scarce. We aimed to assess the utility of SERPINA3 as a prognostic marker in patients hospitalized for chest pain of suspected coronary origin. METHODS: A total of 871 consecutive patients, 386 diagnosed with AMI, were included. Stepwise Cox regression models, applying continuous loge-transformed values, were fitted for the biomarker with all-cause mortality and cardiac death within 2 years or all-cause mortality within the median 7 years as dependent variables. An analysis of MI and stroke, and combined endpoints, respectively, was added. The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model. RESULTS: Plasma samples from 847 patients were available. By 2-year follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. The univariate analysis showed a significant association between SERPINA3 and all-cause mortality (HR 1.41 [95% 1.19-1.68], p < 0.001) but not for cardiac death. Associations after adjustment were non-significant. By 7-year follow-up, 332 (38.1%) patients had died. SERPINA3 was independently associated with all-cause mortality from the third year onward. The HR was 1.14 (95% CI, 1.02-1.28), p = 0.022. Similar results applied to combined endpoints, but not for MI and stroke, respectively. The prognostic value of SERPINA3 was limited to non-AMI patients. No independent associations were noted among AMI patients. CONCLUSIONS: SERPINA3 predicts long-term all-cause mortality but fails to predict outcome in AMI patients.

Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome.

BACKGROUND: Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982). METHODS: A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables. RESULTS: At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months [hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08-1.50) for Norway, and HR 1.57 (95% CI, 1.27-1.95) for Argentina], with similar results at 60 months [HR 1.19 (95% CI, 1.05-1.35) (Norway), and HR 1.56 (95% CI, 1.30-1.88) (Argentina)], and was also significantly associated with cardiac death [HR 1.51 (95% CI, 1.14-2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months [HR 1.39 (95% CI, 1.15-1.68)] and at 60 months [HR 1.43 (95% CI, 1.23-1.67)], enforcing trends in the Norwegian population. CONCLUSIONS: ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402.

Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome.

BACKGROUND: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease. AIM: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information. METHODS: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death. RESULTS: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population. CONCLUSIONS: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.

Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin.

Introduction: Chemokines mediate recruitment and activation of leucocytes. Chemokine ligand 18 (CCL18) is mainly expressed by monocytes/macrophages and dendritic cells. It is highly expressed in chronic inflammatory diseases, and locally in atherosclerotic plaques, particularly at sites of reduced stability, and systemically in acute coronary syndrome patients. Reports on its prognostic utility in the latter condition, including myocardial infarction (MI), are scarce. Aim: To assess the utility of CCL18 as a prognostic marker of recurrent cardiovascular events in patients hospitalized with chest pain of suspected coronary origin. Methods: The population consisted of 871 consecutive chest-pain patients, of whom 386 were diagnosed with acute myocardial infarction (AMI) based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous loge/SD values, were fitted for the biomarkers with cardiac mortality within 2 years and total mortality within 2 and 7 years as the dependent variables. Results: Plasma samples from 849 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. Univariate analysis showed a positive, significant association between CCL18 and total death [HR 1.55 (95% 1.30-1.83), p < 0.001], and for cardiac death [HR 1.32 (95% 1.06-1.64), p = 0.013]. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. CLL18 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.01-1.29), p = 0.030], but not with MI (n = 203) or stroke (n = 55). Conclusion: CCL18 independently predicts long-term all-cause mortality but had no independent prognostic bearing on short-term cardiac death and CVD events.

Long-term prognostic utility of PAPP-A and calprotectin in suspected acute coronary syndrome.

BACKGROUND: Vascular inflammation plays a key role in the development of acute coronary syndrome (ACS). Pregnancy-associated plasma protein A (PAPP-A) and calprotectin are two of several novel promising markers of inflammation. The present study evaluates the prognostic utility of these two biomarkers in patients with suspected ACS. METHODS: Chest pain patients with suspected ACS (N = 871) were consecutively included in a prospective, observational study with a mean follow-up time of 84 months. Blood samples were drawn at admission, prior to treatment with heparin. RESULTS: Total mortality was 38.9%. In univariate analyses, high PAPP-A levels were associated with significant increased mortality. The hazard ratio [HR] in quartile (Q) 3 and Q4 were 1.57 (95% confidence interval (CI), 1.14-2.18), p = 0.006, and 1.41 [95% CI 1.02-1.97], p = 0.040, respectively, as compared to Q1. Calprotectin in the upper quartile (Q4) was associated with total mortality [HR1.94 (95% CI 1.42-2.66)], p = < 0.001, the combined endpoint of death or recurrent myocardial infarction (MI) [HR 1.68 (95% CI 1.26-2.24), p = < 0.001], and recurrent MI [HR 1.60 (95% CI 1.06-2.41); p = 0.024]. However, neither PAPP-A nor calprotectin was found to be an independent predictor of future adverse events. CONCLUSION: In this study, high levels of PAPP-A and calprotectin were associated with adverse clinical outcome in chest pain patients with clinically suspected ACS. However, neither of the two biomarkers was an independent predictor of long-term prognosis.

Re-admission and quality of life among patients with chronic obstructive pulmonary disease after telemedicine video nursing consultation - a randomized study.

Background: Our previous study showed a reduced cumulative length of re-admission stays due to chronic obstructive pulmonary disease (COPD) exacerbations during one year after telemedicine video consultation (TVC). The current study evaluated the effects of TVC on the length of re-admission stays within 12 months follow up post-TVC compared to phone call follow up or COPD usual care in a randomized study. Our secondary aim was to assess the impact of TVC on the frequency of re-admissions within 12 months of follow up. Patient satisfaction, hospital anxiety and depression scale (HADS) and COPD assessment test (CAT) scores were also evaluated. Methods: The study was a prospective randomized study of COPD patients who after hospital discharge for acute COPD exacerbations, were randomized to monitoring by TVC at home compared to phone call follow up for two weeks by a specialist nurse at the hospital or usual COPD care. Prospectively, we compared the cumulative durations and frequencies of hospital re-admissions due to COPD exacerbations within 12 months follow up after TVC, phone call follow up or usual COPD care. Results: Among 173 COPD patients followed for 12 months, 99 were re-admitted. The median cumulative length of readmission stays per patient within 12 months post-TVC did not differ from those followed by phone calls or with usual COPD care. The number of patients re-admitted and the number of re-admissions due to COPD exacerbations were also equal in the three groups. Patient satisfaction was high among those followed by TVC and phone calls, and the HADS and CAT scores favorably declined from baseline to post-intervention in patients followed by TVC and phone calls. Conclusions: The study could not demonstrate a beneficial effect of TVC on the cumulative length of re-admission stays or on the number of re-admissions within 12 months following an acute COPD hospital stay, as compared to those followed by phone calls or with usual COPD care. Patient satisfaction was high among those followed by TVC and phone calls, and the declines in HADS and CAT scores seem to be consequences of increased empowerment and competence for good self-care in COPD patients, remaining through the one-year observation period.

Procollagen type 1 N-terminal propeptide is associated with adverse outcome in acute chest pain of suspected coronary origin.

Background: Extracellular matrix (ECM) is an integral player in the pathophysiology of a variety of cardiac diseases. Cardiac ECM is composed mainly of collagen, of which type 1 is the most abundant with procollagen type 1 N-terminal Propeptide (P1NP) as a formation marker. P1NP is associated with mortality in the general population, however, its role in myocardial infarction (MI) is still uncertain, and P1NP has not been investigated in acute chest pain. The objective of the current study was to assess the role of P1NP in undifferentiated acute chest pain of suspected coronary origin. Methods and results: 813 patients from the Risk in Acute Coronary Syndromes study were included. This was a single-center study investigating biomarkers in consecutively enrolled patients with acute chest pain of suspected coronary origin, with a follow-up for up to 7 years. Outcome measures were a composite endpoint of all-cause death, new MI or stroke, as well as its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. In multivariable Cox regression analysis, quartiles of P1NP were significantly associated with the composite endpoint at 1 year of follow-up with a hazard ratio for Q4 of 1.82 (95% CI, 1.12-2.98). There was no other significant association with outcomes at any time points. Conclusion: P1NP was found to be an independent biomarker significantly associated with adverse clinical outcome at one year in patients admitted to hospital for acute chest pain of suspected coronary origin. This is the first report in the literature on the prognostic value of P1NP in this clinical setting. Clinicaltrialsygov Identifier: NCT00521976.

Podocan and Adverse Clinical Outcome in Patients Admitted With Suspected Acute Coronary Syndromes.

Background: Markers of bone and extracellular matrix (ECM) remodeling may be associated with adverse outcomes in atherosclerotic cardiovascular disease. Podocan is a newly discovered ECM glycoprotein, previously not studied in a chest pain population. We wanted to study the association between Podocan levels on admission and the risk of adverse outcomes in a chest pain population with suspected acute coronary syndromes. Methods: A total of 815 patients from the Risk markers in Acute Coronary Syndrome (RACS) trial with suspected coronary chest pain were followed for 7 years. Blood samples were taken immediately after inclusion and stored in the biobank. Associations between Podocan and endpoints were assessed with Cox proportional hazards analyses. Results: The median admission level of Podocan was 0.674 ng/ml (0.566-0.908 ng/ml). No significant association was found between Podocan quartile levels and all-cause death, neither at 1 year nor 2- or 7-years follow-up (p > 0.05 for all). Furthermore, no significant association could be shown between Podocan and cardiac death, myocardial infarction (MI), stroke, or the composites of all-cause death/MI/stroke or cardiac death/MI/stroke (p > 0.05 for all). Similarly, in a subgroup of patients with Troponin T-positive (n = 432) there was no significant association between Podocan and any of the outcome measures (p > 0.05 for all endpoints and points in time). Conclusion: Podocan, a novel ECM biomarker, is not associated with all-cause mortality or other major cardiovascular adverse events in patients admitted with acute chest pain suspected to be of coronary origin. Clinical Trialsgov Identifier: NCT00521976.

B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina.

BACKGROUND: Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. METHODS: We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. RESULTS: 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively.The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. CONCLUSION: BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS.

A history of late and very late stent thrombosis is not associated with increased activation of the contact system, a case control study.

BACKGROUND: The pathophysiological pathways resulting in Late Stent Thrombosis (LST) remain uncertain. Findings from animal studies indicate a role of the intrinsic coagulation pathway in arterial thrombus formation, while clinical studies support an association with ischemic cardiovascular disease. It is currently unknown whether differences in the state of the contact system might contribute to the risk of LST or Very Late Stent Thrombosis (VLST). We assessed the relation between levels of several components involved in the contact system and a history of LST and VLST, termed (V)LST in a cohort of 20 patients as compared to a matched control group treated with PCI. METHODS AND RESULTS: Activated factor XII (FXIIa), FXII zymogen (FXII), FXIIa-C1-esterase inhibitor (C1-inhibitor), Kallikrein-C1-inhibitor, FXIa-C1-inhibitor and FXIa-alpha1-antitrypsin (AT-inhibitor) complexes were measured by Enzyme-linked immunosorbent assy (ELISA) methodology.Cases and controls showed similar distributions in sex, age, baseline medications and stent type. Patients with a history of (V)LST had a significantly greater stent burden and a higher number of previous myocardial infarctions than the control patients.There were no significant between-group differences in the plasma levels of the components of the contact system. CONCLUSION: In a cohort of patients with a history of (V)LST, we did not observe differences in the activation state of the intrinsic coagulation system as compared to patients with a history of percutaneous coronary intervention without stent thrombosis.

The long pentraxin 3 (PTX3): a novel prognostic inflammatory marker for mortality in acute chest pain.

The long pentraxin 3 (PTX3) is a recently identified member of the pentraxin protein family that includes C-reactive protein. PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli, and elevated plasma levels are found in several conditions including acute coronary syndromes (ACS). The aim of this study was to assess the value of PTX3 as a prognostic marker of mortality and recurrent ischaemic events in a consecutive series of patients admitted with acute chest pain and potential ACS. The patients received follow-up for 24 months. Blood samples were taken on admission for measurement of PTX3, high sensitive C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), and troponin T. All-cause mortality at 24 months in the study cohort was 15.2%. Patients in the upper PTX3 quartiles had a significantly higher death risk than those in the lowest quartile (Q3: hazard ratio [HR] 2.36; 95% CI 1.12-4.99; p = 0.024, and Q4: HR 3.60; 95% CI 1.68-7.72; p = 0.001). Elevated BNP levels were also significantly associated with a fatal outcome (Q3: HR 3.05; 95% CI 1.16-7.99; p = 0.024; and Q4: HR 3.90; 95% CI 1.48-10.26; p = 0.006). Elevation in hsCRP was not associated with increased death risk. As PTX3 predicted mortality independently of BNP, the combination of these two biomarkers showed an incremental prognostic value. PTX3 is a new biomarker related to inflammation that, independently of BNP, strongly predicts long-term all-cause mortality in patients with acute chest pain. The combination of these two biomarkers enhances the prognostic value over either marker alone.

(n-3) Fatty acid content of red blood cells does not predict risk of future cardiovascular events following an acute coronary syndrome.

A reduced risk of fatal coronary artery disease has been associated with a high intake of (n-3) fatty acids (FA) and a direct cardioprotective effect by their incorporation into myocardial cells has been suggested. Based on these observations, the omega-3 index (eicosapentaenoic acid + docosahexaenoic acid in cell membranes of RBC expressed as percent of total FA) has been suggested as a new risk marker for cardiac death. In this study, our aim was to evaluate the omega-3 index as a prognostic risk marker following hospitalization with an acute coronary syndrome (ACS). The omega-3 index was measured at admission in 460 patients with an ACS as defined by Troponin-T (TnT) > or = 0.02 microg/L. During a 2-y follow-up, recurrent myocardial infarctions (MI) (defined as TnT > 0.05 microg/L with a typical MI presentation) and cardiac and all-cause mortality were registered. Cox regression analyses were used to relate the risk of new events to the quartiles of the omega-3 index at inclusion. After correction for age, sex, previous heart disease, hypertension, diabetes, smoking, high-sensitivity C-reactive protein, brain natriuretic peptide, creatinine, total cholesterol, HDL-cholesterol, triacylglycerol, homocysteine, BMI, and medication, there was no significant reduction in risk for all-cause mortality, cardiac death, or MI with increasing values of the index. In conclusion, we could not confirm the omega-3 index as a useful prognostic risk marker following an ACS.

The long-term prognostic value of multiple biomarkers following a myocardial infarction.

INTRODUCTION: We assessed the long-term prognostic value of multiple cardiac biomarkers after an acute myocardial infarction (MI) in order to evaluate a multimarker approach to risk stratification. MATERIAL AND METHODS: Blood samples from 298 patients hospitalized with a myocardial infarction were subsequently tested for NT-proBNP, hsCRP, MMP-9, PAPP-A, MPO, sCD40L and FM. RESULTS: During the median follow-up period of 45 months, 83 patients suffered at least one TnT- positive event. In the unadjusted analysis NT-proBNP predicted future ACS or cardiac death with a hazard ratio (HR) of 1.83 (95% confidence interval (CI), 1.17-2.87, p=0.009) in Q4 as compared to the three lower quartiles (Q1-3). However, NT-proBNP was dependent on chronic heart failure and HDL-cholesterol in the stepwise multivariable model, with a hazard ratio (HR) in Q4 of 1.38 (95% CI, 0.82-2.33, p=0.229). The other biomarkers were not found to be related to the primary event following the index MI. CONCLUSION: In a patient population consisting of 298 subjects hospitalized with a MI, a multimarker approach with NT-proBNP, hsCRP, MMP-9, PAPP-A, MPO, sCD40L and FM rendered no additional prognostic information beyond conventionally used stratification tools in the acute phase. However, this does not preclude clinical valuable prognostic information by a biomarker such as NT-proBNP.

Low levels of cellular omega-3 increase the risk of ventricular fibrillation during the acute ischaemic phase of a myocardial infarction.

AIM OF THE STUDY: Animal studies have demonstrated evidence of an anti-arrhythmic effect of marine n-3 fatty acids (FAs). In humans the same mechanism may explain the observed reduction in sudden cardiac death (SCD) associated with intake of fish. Whether high levels of n-3 FAs could protect against ventricular fibrillation (VF) during the acute ischaemic phase of a myocardial infarction (MI) is, however, not known. MATERIALS AND METHODS: We measured red blood cell content of eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) expressed as a percentage of total FAs (the omega-3 index) at admission in 460 patients hospitalised with an acute coronary syndrome. Out of 265 patients suffering their first MI, 10 (cases) experienced an episode of VF during the initial 6h of symptom onset. The omega-3 index of these patients was compared to that of 185 first-MI patients (controls) free of VF for at least 30 days post-admission. RESULTS: The median value of the omega-3 index in the VF cases was 4.88% as compared to 6.08% in the controls (p=0.013). After adjustment for age, sex, ejection fraction, high-sensitivity C-reactive protein, use of beta-blocker, differences of infarct characteristics and previous angina pectoris, a 1% increase of the omega-3 index was associated with a 48% reduction in risk of VF (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.28-0.96; p=0.037). CONCLUSION: Our study supports an anti-arrhythmic effect of n-3 FAs through their incorporation into myocardial cell membranes, reducing the risk of VF during ischaemia.

The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain.

D-dimer and fibrin monomer both reflect a prothrombotic potential. There are limited data available comparing these two markers of activated coagulation in a prospective manner in an unselected patient population presenting to the emergency department with chest pain. In addition, their role in risk stratification in patients with acute coronary syndrome is still under evaluation. Therefore, we wanted to assess the prognostic value of these markers with respect to long-term all-cause mortality in 871 patients admitted to the emergency department. Blood samples were obtained immediately following admission. After a follow-up period of 24 months, 123 patients had died. In the univariate analysis, both D-dimer and fibrin monomer predicted all-cause mortality within 2 years with an odds ratio of 7.78 (95% confidence interval, 3.95-15.33) and 4.19 (95% confidence interval, 2.42-7.28), respectively, in the highest quartile (Q4) compared with the lowest quartile (Q1). However, in the multivariable logistic regression model for death within 2 years, the odds ratio of D-dimer and fibrin monomer was 1.80 (95% confidence interval, 0.81 to 3.97) and 1.04 (95% confidence interval, 0.53 to 2.04) in Q4 compared with Q1, respectively, and added no prognostic information above and beyond age, known coronary heart disease, B-type natriuretic peptide and the index diagnoses of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina pectoris. In an unselected patient population hospitalized with chest pain and potential acute coronary syndrome, neither D-dimer nor fibrin monomer provided complementary prognostic information to established risk determinants during long-term follow-up.

B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study.

BACKGROUND: Few studies have addressed whether the combined use of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) improves risk stratification for mortality and cardiovascular events in a population with chest pain and suspected acute coronary syndromes (ACS). Therefore, we wanted to assess the incremental prognostic value of these biomarkers with respect to long-term all-cause mortality and recurrent troponin T (TnT) positive cardiac events in 871 patients admitted to the emergency department. METHODS: Blood samples were obtained immediately following admission. RESULTS: After a follow-up period of 24 months, 129 patients had died. The BNP levels were significantly higher among patients dying than in long-term survivors (401 (145-736) versus 75 (29-235) pq/mL [median, 25 and 75% percentiles], p = 0.000). In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) was 5.13 (95% confidence interval (CI), 1.97-13.38) compared to the lowest quartile (Q1) and was associated with all-cause mortality above and beyond age, congestive heart failure and the index diagnosis ST-segment elevation myocardial infarction. HsCRP rendered no prognostic information for all-cause mortality. However, within 30 days, the adjusted HR for patients with recurrent TnT cardiac positive events hsCRP in Q4 was 14.79 (95% CI, 1.89-115.63) compared with Q1 and was associated with recurrent ischemic events above and beyond age, hypercholesterolemia and TnT values at admission. CONCLUSION: BNP may act as a clinically useful biomarker when obtained at admission in an unselected patient population following hospitalization with chest pain and potential ACS, and may provide complementary prognostic information to established risk determinants at long-term follow-up. Our data do not support the hypothesis that the additional assessment of hsCRP will lead to better risk stratification for survival than BNP alone.

Nosocomial outbreak of CTX-M-15-producing E. coli in Norway.

Seven E. coli isolates expressing resistance to 3rd generation cephalosporins were recovered from blood (n=2), kidney and lung tissue (n=1), and urinary tract (n=4) samples from seven patients hospitalised or recently discharged from the Divisions of Geriatrics and Pulmonary Medicine, Central Hospital of Rogaland, between July and September 2004. All isolates expressed a typical ESBL-cefotaximase profile (cefotaxime MIC>ceftazidime MIC) with clavulanic acid synergy. A bla(CTX-M-15) genotype was confirmed in six strains that were coresistant to gentamicin, nitrofurantoin, trimethoprim-sulfamethoxazole and ciprofloxacin. A bla(CTX-M-3) genotype was detected in the last strain. XbaI-PFGE patterns of the six bla(CTX-M-15) isolates revealed a clonal relationship. Bla(CTX-M-15) strains were also positive for the ISEcp1-like insertion sequences that have been shown to be involved in the mobilization of bla(CTX-M.) Further analyses revealed two bla(CTX-M-15)-positive E. coli urinary isolates clonally related to the outbreak strain from two different patients at the same divisions in January and February 2004. These patients were later re-hospitalised and one had E. coli with an ESBL-cefotaximase profile in sputum and nasopharyngeal specimen during the outbreak period. Clinical evaluation suggests that the CTX-M-producing E. coli strains contributed to death in three patients due to delayed efficient antimicrobial therapy. The outbreak emphasises the epidemic potential of multiple-antibiotic-resistant CTX-M-15-producing E. coli also in a country with low antibiotic usage and low prevalence of antimicrobial resistance.

The effect of primary percutaneous coronary intervention as compared to tenecteplase on myeloperoxidase, pregnancy-associated plasma protein A, soluble fibrin and D-dimer in acute myocardial infarction.

INTRODUCTION: Acute coronary reperfusion is accomplished pharmacologically with intravenous thrombolytic therapy or mechanically with primary percutaneous coronary intervention (PCI). METHODS: We have determined the immediate effects of the main coronary reperfusion procedures on the plasma concentrations of myeloperoxidase (MPO), pregnancy-associated plasma protein A (PAPP-A), fibrin monomer (FM) and D-dimer (DD). We studied a total of 38 patients admitted for ST-segment elevation infarct (STEMI). 18 patients were given thrombolytic therapy with tenecteplase and 20 were treated with primary PCI. RESULTS: The plasma concentrations of PAPP-A increased by a factor of six to eight times (p<0.001) following both reperfusion therapies. No significant increase was observed for MPO by either procedure. DD and FM concentrations both increased significantly following thrombolytic therapy, p=0.000, whereas only minor increases, although statistically significant for FM (p=0.013), were noted after PCI. DD and FM were highly correlated prior to the two treatment regimens (R=0.91), and were still highly correlated after PCI (R=0.94) and thrombolytic therapy (R=0.86). No correlation was demonstrated between PAPP-A and markers of activated coagulation. CONCLUSIONS: This is the first report of a significant rise in the plasma concentration of PAPP-A after PCI as compared to thrombolytic treatment (p=0.002) and may indicate a greater impact of PCI than that of thrombolytic therapy on target coronary plaques.

Vitamin D Uptake in Patients Treated with a High-Dosed Purified Omega-3 Compound in a Randomized Clinical Trial Following an Acute Myocardial Infarction.

BACKGROUND: Fish is the natural dietary source of vitamin D. Reports on the influence of purified omega-3 fatty acids on its uptake are scarce. OBJECTIVES: We investigated the impact of a purified high-dose omega-3 compound compared to corn oil on 25-hydroxyvitamin D [25(OH)D] levels following an acute myocardial infarction. METHODS: 228 patients were randomized 1:1 to receive a daily dose of either 4 g omega-3 (OMACOR®) or an equal dose of corn oil, administered double-blindly for 12 months. Total omega-3 and omega-6 measurements were available in 40 randomly picked patients. RESULTS: There was no significant intergroup difference in 25(OH)D changes at 12 months follow-up (p = 0.12), but there was a minor statistical significant intragroup increase in 25(OH)D in both intervention arms (p < 0.001 for n-3 polyunsaturated fatty acids and p = 0.013 for corn oil, respectively). A positive correlation was noted between 25(OH)D and omega-3 prior to inclusion; r = 0.418, p = 0.007, attenuated at 12 months by purified omega-3 intervention; r = 0.021, p = 0.93. No positive correlation was observed between omega-6 and 25(OH)D. CONCLUSION: Long-term treatment with a high dose of purified omega-3 as compared to corn oil did not improve serum concentrations of vitamin D. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT01422317.

The prognostic utility of dihomo-gamma-linolenic acid (DGLA) in patients with acute coronary heart disease.

BACKGROUND: We previously investigated the prognostic utility of red blood cell (RBC) n-3 fatty acids (FAs) in survivors of an acute myocardial syndrome (ACS) but found no relationship with all-cause mortality and cardiac death or MI after two years. Here we extend our follow-up to 7years, focusing on the potential predictive power of RBC n-6 FAs. METHODS: We included 398 ACS patients presenting with increased troponin-T (TnT) levels for whom baseline RBC FA data were available. Cox regression analysis was used to relate the risk of future events to RBC n-6 FA levels, both continuously and by quartile. RESULTS: At 7-year follow-up, 183 (46.0%) had died, 128 (32.2%) had experienced another MI and 24 (6.0%) had had a stroke. Death or MI occurred in 227 patients (57.0%); and death, MI or stroke in 235 patients (59.0%). In a multivariable Cox regression model for total death, the hazard ratio (HR) in the highest as compared to the lowest quartile of dihomo-γ-linolenic acid (DGLA) was 0.55 [95% confidence interval (CI), 0.35-0.88, p=0.012, for death or MI [HR 0.62 (95% CI, 0.41-0.94), p=0.025], and for the fully combined endpoint [HR 0.57 (95% CI, 0.38-0.86), p=0.006]. Similar results were found in the per 1-SD analysis. No other RBC n-6 FAs significantly predicted these outcomes in multivariable models. CONCLUSION: RBC DGLA levels had significant independent prognostic value in post-ACS patients. These findings need confirmation, and the possible biochemical pathways by which higher DGLA membrane levels may be cardioprotective should be explored.