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Background: Hypoxia precedes cardiomyocyte necrosis in acute myocardial infarction (AMI). We therefore hypothesized that uric acid - as a marker of oxidative stress and hypoxia - might be useful in the early diagnosis and risk stratification of patients with suspected AMI., Materials and Methods: In this prospective observational study, uric acid was measured at presentation in 892 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by two independent cardiologists. Patients were followed 24 months regarding mortality. Primary outcome was the diagnosis of AMI, secondary outcome was short- and long-term mortality., Results: Uric acid at presentation was higher in patients with AMI than in patients without (372 μM vs. 336 μM; P < 0·001). The diagnostic accuracy of uric acid for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0·60 (95%Cl 0·56-0·65). When added to cardiac troponin T (cTnT), uric acid significantly increased the AUC of cTnT from 0·89 (95%Cl 0·85-0·93) to 0·92 (95%Cl 0·89-0·95, P = 0·020 for comparison). Cumulative 24-month mortality rates were 2·2% in the first, 5·4% in the second and the third and 15·6% in the fourth quartile of uric acid (P < 0·001 for log-rank). Uric acid predicted 24-month mortality independently. Adding uric acid to TIMI and GRACE risk score improved their prognostic accuracy as shown by an integrated discrimination improvement of 0·04 (P = 0·007) respective 0·02 (P = 0·021)., Conclusions: Uric acid, an inexpensive widely available biomarker, improves both the early diagnosis and risk stratification of patients with suspected AMI., (© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Plaque erosion and plaque rupture occur early in the pathophysiology of acute myocardial infarction (AMI). We hypothesized that markers of plaque instability might be useful in the early diagnosis and risk stratification of AMI., Methods: In this multicenter study, we examined 4 markers of plaque instability, myeloperoxidase (MPO), myeloid-related protein 8/14 (MRP-8/14), pregnancy-associated plasma protein-A (PAPP-A), and C-reactive protein (CRP) in 398 consecutive patients presenting to the emergency department with acute chest pain and compared them to normal and high-sensitivity cardiac troponin T (cTnT and hs-cTnT). The final diagnosis was adjudicated by 2 independent cardiologists. Primary prognostic end point was death during a median follow-up of 27 months., Results: The adjudicated final diagnosis was AMI in 76 patients (19%). At emergency department presentation, concentrations of all 4 biomarkers of plaque instability were significantly higher in patients with AMI than in patients with other diagnoses. However, their diagnostic accuracy as quantified by the area under the ROC curve (AUC) was low (MPO 0.63, MRP-8/14 0.65, PAPP-A 0.62, CRP 0.59) and inferior to both normal and high-sensitivity cardiac troponin T (cTnT 0.88, hs-cTnT 0.96; P<0.001 for all comparisons). Thirty-nine patients (10%) died during follow-up. Concentrations of MPO, MRP-8/14, and CRP were higher in nonsurvivors than in survivors and predicted all-cause mortality with moderate accuracy., Conclusions: Biomarkers of plaque instability do not seem helpful in the early diagnosis of AMI but may provide some incremental value in the risk stratification of patients with acute chest pain.

Objective The early diagnosis of acute myocardial infarction (AMI) can be particularly challenging in patients with known coronary artery disease (CAD) due to pre-existing ECG changes and chronic increases in cardiac troponin (cTn) levels Design Of 1170 consecutive patients presenting with symptoms suggestive of AMI, 433 (37%) with pre-existing CAD were analysed in a prospective multicentre study and the diagnostic and prognostic impact of copeptin in combination with either fourth generation cardiac troponin T (cTnT) or high-sensitivity cTnT (hs-cTnT) was evaluated. Results AMI was the final diagnosis in 78 patients with pre-existing CAD (18%). Copeptin was significantly higher in patients with AMI than in those without (26 pmol/l (IQR 9e71) vs 7 pmol/l (IQR 4e16), p<0.001). The diagnostic accuracy for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was significantly higher for the combination of copeptin and cTnT than for cTnT alone (0.94 vs 0.86, p<0.001). The combination of copeptin and hs-cTnT (0.94) was trending to superiority compared with hs-cTnT alone (0.92, p=0.11). The combination of copeptin and the cTn assays was able to improve the negative predictive value up to 99.5% to rule out AMI. Copeptin was a strong and independent predictor of 1-year mortality (HR 4.18e 4.63). Irrespective of cTn levels, patients with low levels of copeptin had an excellent prognosis compared with patients with raised levels of both copeptin and cTn (360- day mortality 2.8e3.6% vs 23.1e33.8%, p<0.001). Conclusion In patients with pre-existing CAD, copeptin significantly improves the diagnostic accuracy if used in addition to cTnT, but only trended to superiority compared with hs-cTnT alone. Copeptin provides independent prognostic information, largely by overcoming the challenging interpretation of mild increases in hs-cTnT. [ABSTRACT FROM AUTHOR]

Background: Peak oxygen uptake (peak VO2) is a predictor of outcome in patients with lung disease. In these patients, peak VO2 is typically determined by ventilation and gas exchange. However, it is not well known whether cardiac strain contributes to peak VO2 in patients with chronic lung disease. Objective: To assess the relationship between several novel biomarkers reflecting different aspects of cardiac function and peak VO2 in patients with chronic lung disease. Methods: Plasma concentrations of midregional pro-A-type natriuret- ic peptide (MR-proANP), midregional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and C-terminal provasopressin (copeptin) were measured in 85 patients with a variety of chronic pulmonary diseases [age 57 ± 14 years, forced expiratory volume in the 1st second (FEV1) 76 ± 23% of the predicted value] undergoing maximal cardiopulmonary exercise testing (peak VO2 18.6 ± 6.6 ml/kg/min). Results: Raised MR-proANP (r = -0.54), MR- proADM (r = -0.54), and CT-proET-1 (r = -0.49; p < 0.001 for all) but not copeptin (r = -0.05; p = 0.68) concentrations were associated with lower peak VO2, and these associations were independent of age, gender, medication, FEV1 and oxygenation. The relationship between MR-proANP, MR-proADM, and CT-proET-1 and peak VO2 was significant whether patients had an obstructive ventilatory disease or not. Conclusions: In patients with chronic lung disease, several biomarkers known to reflect measures of cardiac function were associated with peak VO2 independent of lung function, indicating that cardiac strain may contribute to exercise limitation in these patients due to concomitant cardiac disease or in the context of a pulmonary-cardiac interaction. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: The purpose of this study was to investigate the utility of mid-regional pro-adrenomedullin (MR-proADM) in the early diagnosis and risk stratification of patients with acute chest pain in comparison with established and novel biomarkers and risk scores. Methods: In this prospective, observational, international, multi-center trial (APACE), MR-proADM was determined in 1179 unselected patients with acute chest pain. Patients were followed for 24months. Results: MR-proADM concentrations at presentation were higher in patients with AMI (median: 0.78nmol/l, IQR 0.60–1.13) than in patients with other diagnoses (0.64nmol/l, IQR 0.49–0.86nmol/l; p<0.001). The diagnostic accuracy of MR-proADM for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.66. Adding MR-proADM to hs-cTnT could not improve its diagnostic accuracy for AMI (p=0.431). Seventy-six percent of all deaths occurred in the fourth quartile of MR-proADM (>0.90nmol/l). Adding MR-proADM to the TIMI-score (AUC 0.87) predicted 1-year mortality more accurately than the TIMI-score alone (AUC 0.82; p<0.001). Net reclassification improvement (TIMI vs. additionally MR-proADM) amounted to 0.137 (p=0.012). MR-proADM had higher prognostic accuracy as compared to hs-cTnT in patients with AMI (p=0.015) and in those without AMI (p=0.003). MR-proADM at presentation was tantamount to GRACE score and BNP as to its prognostic accuracy for mortality. The AUC for the prediction of cardiovascular events amounted to 0.63. Conclusions: While MR-proADM does not have clinical utility in the early diagnosis of AMI or predicting cardiovascular events in patients with acute chest pain, it may provide prognostic value for all-cause mortality. [Copyright &y& Elsevier]

Abstract: Background: Patients with acute chest pain having serial undetectable cardiac troponin (cTn) levels, as measured with conventional assays, are considered at very low risk. The aim of this multicenter study was to determine the accuracy of multiple biomarkers in these patients. Methods: We enrolled 1247 consecutive patients with suspected AMI. Of these, 325 had undetectable levels of cTnT (Roche, 4th generation assay) at presentation and at 6h. Fourteen novel markers quantifying cardiomyocyte damage, inflammation and/or plaque rupture, and neurohormonal activation were measured at presentation. The occurrence of death or acute myocardial infarction (AMI) (primary end point) and unplanned coronary revascularization (secondary endpoint) were recorded during long-term follow-up. Results: During a mean follow-up of 668±241days, death/AMI occurred in 23 patients (7%), unplanned revascularization in 46 (14%). Among all biomarkers, high-sensitive cTnT (hs-cTnT), Midregional pro-adrenomedullin (MR-proADM) and growth differentiation factor-15 (GDF-15) were independently associated with future death/AMI; hs-cTnT was 0.013 (0.008–0.017) μg/l versus 0.006 (0.003–0.010) μg/l, MR-proADM was 0.78 (0.66–1.09) nmol/l versus 0.60 (0.18–0.80) nmol/l and GDF-15 was 1800 (1600–2200) ng/l versus 1100 (800–1700) ng/l in patients with versus without death/AMI during follow-up (p <0.001 each). The area under the receiver-operating characteristics curve to predict death/AMI was 0.73 (95%CI 0.63–0.83) for hs-cTnT, 0.71 (95% CI 0.62–0.81) for MR-proADM and 0.78 (95%CI 0.71–0.86) for GDF-15. Conclusion: Patients with serial undetectable levels of cTnT using the contemporary 4th generation assay are at low but not negligible risk of future cardiac events. Hs-cTnT, MR-proADM and/or GDF-15 might help to further improve risk-stratification in this group. [Copyright &y& Elsevier]