Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial.

BACKGROUND: The cardiovascular benefit from n-3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear. OBJECTIVES: To assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events. METHODS: In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all-cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new-onset atrial fibrillation (AF). RESULTS: EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on-treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high-density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on-treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75-0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07-1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66-1.06] for MACE and 1.39 [0.90-2.13] for AF). CONCLUSION: Greater on-treatment increases in EPA were associated with lower risk of MACE and higher risk of new-onset AF. These data suggest that the cardiovascular effects of increasing n-3 PUFA levels through supplements are complex, involving both potential benefits and harm.

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.

N-terminal pro-B-type natriuretic peptide as a prognostic indicator for 30-day mortality following out-of-hospital cardiac arrest: a prospective observational study.

BACKGROUND: Early risk stratification applying cardiac biomarkers may prove useful in sudden cardiac arrest patients. We investigated the prognostic utility of early-on levels of high sensitivity cardiac troponin-T (hs-cTnT), copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a prospective observational unicenter study, including patients with OHCA of assumed cardiac origin from the southwestern part of Norway from 2007 until 2010. Blood samples for later measurements were drawn during cardiopulmonary resuscitation or at hospital admission. RESULTS: A total of 114 patients were included, 37 patients with asystole and 77 patients with VF as first recorded heart rhythm. Forty-four patients (38.6%) survived 30-day follow-up. Neither hs-cTnT (p = 0.49), nor copeptin (p = 0.39) differed between non-survivors and survivors, whereas NT-proBNP was higher in non-survivors (p <  0.001) and significantly associated with 30-days all-cause mortality in univariate analysis, with a hazard ratio (HR) for patients in the highest compared to the lowest quartile of 4.6 (95% confidence interval (CI), 2.1-10.1), p <  0.001. This association was no longer significant in multivariable analysis applying continuous values, [HR 0.96, (95% CI, 0.64-1.43), p = 0.84]. Similar results were obtained by dividing the population by survival at hospital admission, excluding non-return of spontaneous circulation (ROSC) patients on scene [HR 0.93 (95% CI, 0.50-1.73), P = 0.83]. We also noted that NT-proBNP was significantly higher in asystole- as compared to VF-patients, p <  0.001. CONCLUSIONS: Early-on levels of hs-cTnT, copeptin and NT-proBNP did not provide independent prognostic information following OHCA. Prediction was unaffected by excluding on-scene non-ROSC patients in the multivariable analysis. TRIAL REGISTRATION: ClinicalTrials. gov, NCT02886273 .

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.

Dietary intake of n-3 long-chain polyunsaturated fatty acids and risk of myocardial infarction in coronary artery disease patients with or without diabetes mellitus: a prospective cohort study.

BACKGROUND: A beneficial effect of a high n-3 long-chain polyunsaturated fatty acid (LCPUFA) intake has been observed in heart failure patients, who are frequently insulin resistant. We investigated the potential influence of impaired glucose metabolism on the relation between dietary intake of n-3 LCPUFAs and risk of acute myocardial infarction (AMI) in patients with coronary artery disease. METHODS: This prospective cohort study was based on the Western Norway B-Vitamin Intervention Trial and included 2,378 patients with coronary artery disease with available baseline glycosylated hemoglobin (HbA1c) and dietary data. Patients were sub-grouped as having no diabetes (HbA1c <5.7%), pre-diabetes (HbA1c ≥5.7%), or diabetes (previous diabetes, fasting baseline serum glucose ≥7.0, or non-fasting glucose ≥11.1 mmol/L). AMI risk was evaluated by Cox regression (age and sex adjusted), comparing the upper versus lower tertile of daily dietary n-3 LCPUFA intake. RESULTS: The participants (80% males) had a mean age of 62 and follow-up of 4.8 years. A high n-3 LCPUFA intake was associated with reduced risk of AMI (hazard ratio 0.38, 95%CI 0.18, 0.80) in diabetes patients (median HbA1c = 7.2%), whereas no association was observed in pre-diabetes patients. In patients without diabetes a high intake tended to be associated with an increased risk (hazard ratio1.45, 95%CI 0.84, 2.53), which was significant for fatal AMI (hazard ratio 4.79, 95%CI 1.05, 21.90) and associated with lower HbA1c (mean ± standard deviation 4.55 ±0.68 versus 4.92 ±0.60, P = 0.02). No such differences in HbA1c were observed in those with pre-diabetes or diabetes. CONCLUSIONS: A high intake of n-3 LCPUFAs was associated with a reduced risk of AMI, independent of HbA1c, in diabetic patients, but with an increased risk of fatal AMI and lower HbA1c among patients without impaired glucose metabolism. Further studies should investigate whether patients with diabetes may benefit from having a high intake of n-3 LCPUFAs and whether patients with normal glucose tolerance should be careful with a very high intake of these fatty acids. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov as NCT00354081.

Coronary reperfusion and clinical outcomes after thrombus aspiration during primary percutaneous coronary intervention: findings from the HORIZONS-AMI trial.

OBJECTIVES: To assess the quality of coronary reperfusion and long-term clinical outcomes of patients enrolled in the HORIZONS-AMI trial according to the use of thrombus aspiration (TA). BACKGROUND: The impact of manual TA on microvascular perfusion and clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is unsettled. METHODS: In this retrospective, nonrandomized, subgroup analysis, the authors evaluated thrombolysis in myocardial infarction (TIMI) flow, tissue myocardial perfusion grade (TMPG), ST-segment resolution (STR), net adverse clinical events (NACE), and major adverse cardiac events (MACE) in patients undergoing pPCI with or without manual TA. RESULTS: A total of 318 patients had pPCI with upfront TA, and 2,917 patients had pPCI without TA. Patients who had TA were more likely to have TIMI 0/1 flow at baseline (75.1% vs. 63.7%, P < 0.0001). There was no difference in the rates of final TIMI 3 flow (90.2% vs. 92.3%, P = 0.19) or dynamic TMPG 2-3 (77.4% vs. 76.4%, P = 0.68). STR ≥70% was similar in both groups at 60 minutes but higher in the TA group at discharge (71.8% vs. 64.6%, P = 0.02). After multivariable adjustment, TA did not predict MACE at 30 days (HR 0.96 [0.51-1.80], P = 0.90), 1 year (HR 1.03 [0.68-1.55], P = 0.89), or 3 years (HR 1.13 [0.86-1.48], P = 0.39). Stent thrombosis did not differ at 1 year or 3 years. CONCLUSIONS: In STEMI patients undergoing pPCI, the use of manual TA was associated with improved STR at discharge, but not with any difference in final TIMI flow, TMPG, or MACE.

Cardiac resynchronization therapy improves minute ventilation/carbon dioxide production slope and skeletal muscle capillary density without reversal of skeletal muscle pathology or inflammation.

AIMS: We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology and inflammation in patients with heart failure. METHODS AND RESULTS: Stable patients (n = 21, 14 males, mean age 70 ± 7 years) with symptomatic heart failure (mean left ventricular ejection fraction 24 ± 6%) and an indication for CRT were included. Ergospirometry, skeletal muscle open biopsy, and blood sampling were performed prior to implantation and after 6 months of CRT. After CRT there was a reduction in both left ventricular end-diastolic diameter (LVEDD; 6.8 ± 0.8 vs. 6.3 ± 0.7 cm, P < 0.001) and native QRS duration (D) minus biventricular paced QRSD (172.9 ± 23 vs. 136.3 ± 23 ms, P ≤ 0.001). These changes were associated with an increase in peak slope oxygen uptake (consumption) (VO2) (13.3 ± 2.2 vs. 14.5 ± 2.6 mL/kg/min, P = 0.07) and an improvement in the minute ventilation/carbon dioxide production slope (VE/VCO2) slope (41.6 ± 7.4 vs. 39.1 ± 5.6, P = 0.012). There were no statistically significant changes in levels of pro-inflammatory cytokines, in mediators of mitochondrial biosynthesis or skeletal muscle pathology, except for an increase in skeletal muscle capillary density (4.5 ± 2.4 vs. 7.7 ± 3.3%, P = 0.002). Both the reduction of QRS duration and the increase in peak VO2 correlated significantly with the change in mitochondrial density (r = 0.57, P = 0.008 and r = 0.54, P = 0.027, respectively). CONCLUSION: Cardiac resynchronization therapy, with improved functional status and reduced LVEDD resulted in increased peak VO2, improvement in VE/VCO2 slope and capillary density in skeletal muscle, with no reduction in systemic pro-inflammatory cytokines, increase in intramuscular levels of mediators of mitochondrial biosynthesis or improvement in skeletal muscle ultrastructure per se. ClinicalTrials.gov Identifier: NCT01019915.

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.

Omega-3 index and prognosis in acute coronary chest pain patients with a low dietary intake of omega-3.

BACKGROUND: The omega-3 index (eicosapentaenoic acid + docosahexaenoic acid) content in red blood cell membranes has been suggested as a novel risk marker for cardiac death. Objective. To assess the ability of the omega-3 index to predict all-cause mortality, cardiac death and sudden cardiac death following hospitalization with an acute coronary syndrome (ACS), and to include arachidonic acid (AA) in risk assessment. MATERIAL AND METHODS: The omega-3 index was measured in 572 consecutive patients (median 63 years and 59% males) admitted with chest pain and suspected ACS in an inland Northern Argentinean city with a dietary habit that was essentially based on red meat and a low intake of fish. Clinical endpoints were collected during a 5-year follow-up period, median 3.6 years, range 1 day to 5.5 years. Stepwise Cox regression analysis was employed to compare the rate of new events in the quartiles of the omega-3 index measured at inclusion. Multivariable analysis was performed. RESULTS: No statistical significant differences in baseline characteristics were noted between quartiles of the omega-3 index. The median of the adjusted omega-3 index was 3.6%. During the follow-up period, 100 (17.5%) patients died. Event rates were similar in all quartiles of the omega-3 index, with no statistical significant differences. AA added no prognostic information. CONCLUSION: In a population with a low intake of fish and fish oils, the adjusted omega-3 index did not predict fatal events following hospitalization in patients with acute chest pain and suspected ACS.

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.

The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease.

BACKGROUND: Vorapaxar has been shown to reduce cardiovascular mortality in post-myocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. AIM: This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days' FU and beyond, in patients with coronary heart disease. METHODS: Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at -80°C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and -2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). RESULTS: A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1-month FU (p = 0.034). Angiopoietin-like 4 increased (p = 0.028) and plasminogen activator inhibitor-2 decreased (p = 0.025) in favor of vorapaxar at final FU. In post-MI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p = 0.029. Also, a short-term increase in von Willebrand factor (p = 0.032) favoring vorapaxar was noted in NSTEMI patients. CONCLUSION: Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients.

The heart rate of ventricular tachycardia following an old myocardial infarction is inversely related to the size of scarring.

AIMS: The purpose of the study was to examine the relationship between the initial cycle length (CL) of ventricular tachycardia (VT) and the size of the myocardial scar and its border zone in patients with old myocardial infarction (MI). METHODS AND RESULTS: Late gadolinium-enhancement cardiac magnetic resonance was performed prior to implantable cardioverter-defibrillator (ICD) implantation in 24 patients. The size of non-scared myocardium, scar, scar core, and border zone were measured as voxel numbers. The number of core islands, contour-regularity of scar and left-ventricular ejection fraction were also calculated. During the first year after ICD implantation, VT was recorded in 20 patients. With univariate regression analysis, the number of core islands had the highest correlation with the CL of VT (R = 0.614, adjusted R(2) = 0.342, P = 0.004). By multiple regression analyses, the highest correlation was found by the use of scar core and core islands (R = 0.721, adjusted R(2) = 0.464, P = 0.002). CONCLUSION: The heart rate of VT (bpm) in patients with old MI is inversely related to the properties of the densest parts of the myocardial scar.

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.

Activated factor XI-antithrombin complex presenting as an independent predictor of 30-days mortality in out-of-hospital cardiac arrest patients.

BACKGROUND: Cardiac arrest and cardiopulmonary resuscitation (CPR) are associated with activated coagulation and microvascular fibrin deposition with subsequent multiorgan failure and adverse outcome. OBJECTIVES: Activated Factor XI-antithrombin (FXIa-AT) complex, activated Factor IX-antithrombin (FIXa-AT) complex and thrombin-antithrombin (TAT) complex were measured as markers of coagulation activation, and evaluated as independent prognostic indicators in out-of-hospital cardiac arrest (OHCA) patients. METHODS: From February 2007 until December 2010 blood samples were collected in close approximation to CPR from patients with OHCA of assumed cardiac origin. Follow-up samples in survivors were drawn 8-12 h and 24-48 h after hospital admission. All measurements were determined by ELISA. RESULTS: Thirty-seven patients presented with asystole and 77 with ventricular fibrillation as first recorded heart rhythm. At 30-days follow-up, 70 patients (61.4%) had died. All patients had elevated levels of FXIa-AT complex, FIXa-AT complex and TAT. Initial levels were significantly higher in non-survivors compared to 30-days survivors. A significant increase in risk of 30-days all-cause mortality was observed through increasing quartiles of all three biomarkers in univariate Cox regression analysis. Compared to the lowest quartile (Q1), only FXIa-AT complex levels in Q3 (HR 3.17, p = 0.011) and Q2 (HR 3.02, p = 0.016) were independently associated with all-cause mortality in the multivariable analysis. FIXa-AT complex and TAT-complex did not behave as independent predictors. CONCLUSIONS: Complexes of FXIa-AT were independently associated with 30-days survival in OHCA-patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov, NCT02886273.

Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT).

INTRODUCTION: Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). MATERIALS AND METHODS: NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008-11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3-5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models. RESULTS: The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15). CONCLUSIONS: The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. CLINICAL TRIAL REGISTRATION: Unique identifier NCT00811772; http://www.clinicaltrial.gov.

A comparison of the health status after percutaneous coronary intervention at a hospital with and without on-site cardiac surgical backup: a randomized trial in nonemergent patients.

BACKGROUND: Prospective randomized trials comparing the coronary artery disease-related health status outcomes (changes in symptom grade, physical functional capacity and health-related quality of life) after percutaneous coronary intervention at hospitals with and without on-site cardiac surgical backup have not been reported earlier. METHODS: We randomly assigned 609 consecutive patients fulfilling pre-specified procedural low-risk criteria to undergo percutaneous coronary intervention at either a community hospital without or a regional hospital with on-site surgical backup. Five hundred and seventy-six patients completed the health status evaluation at baseline and at 6 months follow-up. RESULTS: At baseline, 91.4% had symptoms, and the mean (standard deviation) Canadian Cardiovascular Society's classification was 2.5 (0.9). The procedural success rates and the changes in health status measures were similar at the two hospitals. Overall there was a substantial relief of symptoms with a reduction in Canadian Cardiovascular Society's classification of 1.9 (1.2), increase in exercise time [1.4 (1.9) min] and reduction in use of antianginal drugs [0.6 (0.9) less drugs] at follow-up compared with baseline (all P<0.001). Health-related quality of life was evaluated with the Short-Form 36 health survey. There were significant and similar improvements in nearly all multi-item and summary scores from baseline to follow-up at the two hospitals. The largest improvements were seen in items related to physical functioning [overall change in Physical Component Score from baseline to follow-up 6.9 (9.1) points, P<0.001] and lowest in the mental health domains [change in Mental Component Score 3.3 (10.7) points, P<0.001]. INTERPRETATION: This study shows that a substantial and comparable gain in coronary artery disease-related health status can be achieved at hospitals both with and without surgical backup.

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.