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.

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 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 years 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 years follow-up, 332 (38.1%) patients had died. SERPINA3 was independently associated with all-cause mortality from the third year onwards. 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 failed to predict outcome in AMI patients.

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.

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.

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.

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.

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.

Suggested Cut-Off Values for Vitamin D as a Risk Marker for Total and Cardiac Death in Patients with Suspected Acute Coronary Syndrome.

BACKGROUND: Several studies have demonstrated an association between low vitamin D levels and cardiovascular risk. Vitamin D cut-off levels are still under debate. OBJECTIVES: To assess two cut-off levels, 40 and 70 nmol/L, respectively, for vitamin D measured as 25-hydroxyvitamin D in chest pain patients with suspected acute coronary syndrome. METHODS: We investigated 1853 patients from coastal-Norway and inland Northern-Argentina. A similar database was used for pooling of data. Two-year follow-up data including all-cause mortality, cardiac death, and sudden cardiac death in the total patient population were analyzed, applying univariate and multivariable analysis. RESULTS: Two hundred fifty-five patients with known vitamin D concentrations died. In the multivariable analysis, there was a decrease in total mortality above a cut-off level of 40 nmol/L and a decrease in cardiac death above a cut-off level of 70 nmol/L [HRs of 0.66 (95% CI, 0.50-0.88), p = 0.004 and 0.46 (95% CI, 0.22-0.94), p = 0.034, respectively]. CONCLUSION: Vitamin D cut-off levels of 40 and 70 nmol/L were related to total mortality and cardiac death, respectively.

Long-term prognostic utility of pentraxin 3 and D-dimer as compared to high-sensitivity C-reactive protein and B-type natriuretic peptide in suspected acute coronary syndrome.

BACKGROUND: Vascular inflammation plays a key role in the development of atherosclerosis and acute coronary syndrome (ACS), and pentraxin 3 (PTX3) is one of several novel, promising markers of inflammation. In addition, D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. The present study assesses the prognostic utility of these two biomarkers as compared to high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP), in addition to conventional clinical risk factors for coronary heart disease in patients with suspected ACS. METHODS: Chest pain patients with suspected ACS (n = 871) were consecutively included in a prospective, observational study with a follow-up time of 84 months. RESULTS: At 7-year follow-up, 332 patients had died and 203 had suffered an adverse troponin T-positive, non-fatal cardiac event. In the multivariate analysis, levels of PTX3 above 5.88 ng/mL (median) and D-dimer above 436 µg/L (lower limit upper quartile) independently predicted mortality (HR 1.60 [95% CI 1.10-2.33]; p = 0.014 and HR 1.83 [95% CI 1.20-2.78]; p = 0.005, respectively). Also, BNP levels above 310.75 pg/mL (lower limit upper quartile) (HR 2.16 [95% CI 1.37-3.42]; p = 0.001), but not hsCRP, independently predicted mortality. Only hsCRP and BNP also predicted future myocardial infarction (HR 1.59 [95% CI 1.05-2.40]; p = 0.029 and HR 1.91 [95% CI 1.10-3.31]; p = 0.021, respectively). CONCLUSION: High levels of PTX3, D-dimer and BNP were found to be independent, long-term predictors of all-cause mortality in chest pain patients with a suspected ACS. hsCRP and BNP also predicted future myocardial infarction.

Borderline Values of Troponin-T and High Sensitivity C-Reactive Protein Did Not Predict 2-Year Mortality in TnT Positive Chest-Pain Patients, Whereas Brain Natriuretic Peptide Did.

BACKGROUND: Troponin-T (TnT), high-sensitive C-reactive protein (hsCRP), and Brain Natriuretic Peptide (BNP) have been shown to be independent prognostic indicators of total and cardiac death during short- and long-term follow-up. METHODS: We investigated prospectively the prognostic value of admission samples of TnT, hsCRP, and BNP in 871 chest-pain patients from South-Western Norway and 982 patients from Northern Argentina, based on a similar protocol and database setup. Follow-up was 2 years for the pooled population. The prognostic value of the selected biomarkers was investigated in quartiles of 239 patients with TnT values greater than 0.01 and up to and including 0.1 ng/mL, with continuous TnT as a potential confounder. RESULTS: After 24 months, 69 patients had died, of whom 38 died from cardiac causes. In the selected range of TnT, this biomarker was not significantly different between patients who died and survived (mean 0.0452 and 0.0457, p = 0.887). The BNP levels were significantly higher among patients dying than in long-term survivors [340 (142-656) versus 157 (58-367) pg/mL (median, 25 and 75% percentiles), p < 0.001]. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) as compared to the lowest (Q1) was significantly related to total mortality [HR 2.84 (95% confidence interval (CI), 1.13-7.17)], p = 0.027, in addition to age (p ≤ 0.001) and hypercholesterolemia (p = 0.043). For cardiac death, the HR for BNP was 5.18 (95% CI, 1.06-25.3), p = 0.042. Several other variables (age, congestive heart failure, ST elevation myocardial infarction, and study country) were also significantly related to cardiac death. In a multivariable Cox regression model, hsCRP rendered no significant prognostic information for all-cause mortality (p = 0.089) or for cardiac mortality (p = 0.524). CONCLUSION: In patients with borderline TnT values (greater than 0.01 and up to and including 0.1 ng/mL), this biomarker as well as hsCRP did not render prognostic information, whereas BNP was found to be a strong prognostic indicator of 2-year total and cardiac mortality.

Prognostic utility of vitamin D in acute coronary syndrome patients in coastal Norway.

BACKGROUND: An inverse relationship between cardiovascular risk and levels of vitamin D and omega-3 index may exist. OBJECTIVES: To evaluate the prognostic utility of serum 25-hydroxyvitamin D [25(OH)D] in 871 patients with suspected acute coronary syndrome (ACS) and to assess the seasonal correlation between 25(OH)D and the omega-3 index in 456 ACS patients from southwestern Norway. RESULTS: In the univariate analysis the hazard ratio (HR) at 2-year follow-up for all-cause mortality in the highest as compared to the lowest quartile of 25(OH)D in the total population was 0.61 (95% confidence interval (CI), 0.37-1.00), P = 0.050. At 7-year follow-up, the corresponding HR for all-cause mortality was 0.66 (95% CI, 0.49-0.90), P = 0.008, and for females alone 0.51 (95% CI, 0.32-0.83), P = 0.006. Quartile survival did not differ in the multivariable analysis, whereas 25(OH)D < 40 nM (<16 ng/mL) was found to be independently related to mortality. Seasonal differences in 25(OH)D, but not for the omega-3 index, were noted, and the two biomarkers were positively correlated, especially during winter-spring; Pearson's correlation coefficient was 0.358, P < 0.001. CONCLUSION: Vitamin D levels are related to survival, especially in females, and correlate with the omega-3 index.

Re-admissions to hospital and patient satisfaction among patients with chronic obstructive pulmonary disease after telemedicine video consultation - a retrospective pilot study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of acute hospital admissions. The main object of our study was to evaluate the effects of telemedicine video-consultation (TVC) on the frequency of hospital re-admissions due to COPD exacerbations. Our secondary aim was to assess the impact of TVC on the length of re-admission stays within 6 and 12 months follow up after TVC. Patient satisfaction was also evaluated. METHODS: The study was a retrospective observational study of COPD patients who after hospital discharge or during outpatient treatment for acute COPD exacerbations, were monitored for 2 weeks by TVC at home by a specialist nurse at the hospital during a pilot project period. Retrospectively, we compared the frequencies (chi-square test) and durations of hospital re-admissions (paired t-test) due to COPD exacerbations within 6 and 12 months follow up after TVC to comparable events 6 and 12 months prior to TVC. RESULTS: Among 99 patients followed for 6 months after TVC, 56 were followed for totally 12 months. The number of patients re-admitted and the number of re-admissions due to COPD exacerbations were not reduced within 6 or 12 months post-TVC, as compared to 6 and 12 months pre-TVC.The mean length of re-admission stays within 12 months post-TVC was markedly reduced as compared to pre-TVC. Patients hospitalised the last 6 and 12 months pre-TVC, had significantly shorter re-admission stays, p = 0.033 and p = 0.001, respectively. Patient satisfaction was high. CONCLUSION: Despite the failure to demonstrate reduced frequency of re-admissions within 6 and 12 months post-TVC, the re-admission length within 12 months post-TVC was markedly reduced as compared to pre-TVC. The patient satisfaction was high. Future prospective, randomised, controlled trials must be performed before TVC can be recommended in COPD management.

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.

The role of long-chained marine N-3 polyunsaturated Fatty acids in cardiovascular disease.

This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.

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.

Activated factor XII type A and B-type natriuretic peptide are complementary and incremental predictors of mortality in patients following admission with acute coronary syndrome.

The aim of this analysis was to assess the predictive value of activated factor XII type A (XIIaA) and B-type natriuretic peptide (BNP) in acute coronary syndrome patients stratified according to troponin release and to evaluate their complementary utility as predictors of all-cause mortality and recurrent troponin T (TnT)-positive events. Multivariable analysis in 870 patients admitted with suspected myocardial infarction was performed using the Cox proportional hazard ratio model. Variables in the model included XIIaA and BNP as well as conventional risk factors for mortality. Although both XIIaA and BNP were identified as independent predictors for all-cause mortality in the total group of patients, only BNP was found to be an independent predictor for all-cause mortality in patients with a confirmed myocardial infarction (TnT > 0.05 ng/ml) at admission (hazard ratio 4.24, 95% confidence interval 1.28-14.07), whereas only XIIaA was an independent predictor for all-cause mortality in patients with low TnT release (0.01 < TnT < or = 0.05 ng/ml) at admission (hazard ratio 10.37, 95% confidence interval 2.89-37.21). The combination of these two biomarkers provided complementary prognostic information for all-cause mortality as compared with each of the biomarkers alone in the total patient material. XIIaA is particularly useful in predicting mortality in acute coronary syndrome patients with low troponin release, whereas BNP is effective in predicting mortality in patients with confirmed myocardial infarction and more substantial troponin release. The combination of these two biomarkers improves outcome prediction in unselected patients with chest pain and acute coronary syndrome.

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.