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Background: Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome. Methods: GDF-15 concentrations were measured in 1945 patients who were recruited between 2002 and 2009 to the Coronary Disease Cohort Study. For this analysis, follow-up was curtailed at 10 years and association of GDF-15 with all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure hospitalizations were assessed with multivariate Cox proportional hazard regression analysis. Results: After 10 years of follow-up, there were 648 deaths (348 from cardiovascular causes), 500 admissions for myocardial infarction, and 436 for heart failure. Four-month convalescent GDF-15 demonstrated a robust independent association with all endpoints, which remained after adjustment for Global Registry of Acute Coronary Events score and other convalescent biomarkers. When compared to the lowest quartile of GDF-15 concentrations, those in the highest quartile had a 3-fold increased risk of all-cause death. Conclusions: Convalescent plasma GDF-15 is a strong and independent predictor of 10-year all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure admission following an acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Background: It is well known that plasma creatinine concentration is affected by muscle mass, while some studies have suggested cystatin C is affected by body mass index (BMI). Our aim was to assess the effects of lean versus fat mass on cystatin C and creatinine derivative equations in estimating glomerular filtration rate (GFR) in healthy young men. Methods: Three groups of participants were studied: those classified as normal (BMI 18-25 kg/m2 with body fat ,30%); muscular subjects (BMI .30 kg/m2 and body fat ,20%); and obese subjects (BMI .30 kg/m2 and body fat .30%). All underwent diethylenetriamine pentaacetic acid GFR, bio-electrical impedance and dual-energy X-ray absorptiometry body composition analysis, measurement of plasma cystatin C, creatinine and high-sensitivity C-reactive protein and completed a diet record. Results: Cystatin C was highest in the obese group (0.77 mg/L; 95% confidence intervals [CI] 0.69-0.77) and creatinine was highest in the muscular group (90.1 mmol/L; 95% CI 84.3-96.0). On multivariate analysis, body fat and GFR (P = 0.003) were significant determinants of cystatin C; muscle mass and age affected creatinine significantly (P = 0.02). Using cystatin C equations, Le Bricon and Hoek showed significantly lower estimated GFR in the obese group but performed reasonably well within 50%, 30% and 20% of GFR. Creatinine equations showed significant underestimations of GFR for the muscular group. Conclusions: Body fat is a significant determinant of cystatin C while creatinine concentration is highly affected by muscle mass and age. Body composition plays an important role in the interpretation of renal function. Cystatin C equations are still accurate in predicting GFR in our healthy male group without chronic kidney disease. [ABSTRACT FROM AUTHOR]

Introduction: Soluble urokinase plasminogen activator receptor (suPAR) is a circulating protein believed to be responsible for immune dysfunction leading to plague vulnerability. Its use in heart failure (HF) populations is unclear. We report on the prognostic utility of suPAR in patients presenting with acute breathlessness suspicious of acute HF. Methods: Plasma suPAR were determined in 333 patients presenting to hospital with breathlessness and in 155 separate healthy volunteers. Acute HF was adjudicated by two cardiologists blinded to all results, bar NT-proBNP. Plasma samples taken at hospital presentation were interrogated for suPAR (CE marked ELISA, Virogates), hsTnT and NT-proBNP (Roche Cobas), complete with 1 yr follow up data. Results: In 155 healthy volunteers (median age: 47 yr, IQR: 31-57, 50% female), median suPAR was 2.0 ng/mL, IQR; 1.7-2.3, and correlated with age (Spearman's r=0.310, p<0.0001), eGFR (r=-0.285, p<0.0001), and NT-proBNP (r=0.407, p<0.0001), but not BMI. In the breathless cohort (median age: 73 yr, IQR: 62-81, 56% female), 33% had ADHF, 14.7% with pneumonia, and 26.7% with COPD. Plasma suPAR were higher in those who died at 1 yr, new HF at 1 yr, or in those presenting with ADHF, and separately pneumonia (Figure). suPAR had strong 1 yr prognostic ability to predict death (ROC=0.719, n=70, p<0.0001), new HF (ROC=0.707, n=59, p<0.0001) and the composite death/HF at 1 yr (ROC=0.733, n=104, p<0.0001). suPAR could improve the mortality prediction at 1 yr for ROC hsTnT (0.729 to 0.741) and NT-proBNP (0.695 to 0.729), but did not assist the prediction of HF. After adjustment for conventional risk factors, suPAR outperformed both hsTnT and NT-proBNP (p=0.04), at predicting death in those with ADHF (n= 22). Conclusions: These novel results show suPAR as a strong biomarker that will provide beneficial prognostic information in patients who are at risk of death, especially when combined with hsTnT and NT-proBNP. suPAR may provide superior performance to current candidate cardiac biomarkers in risk management. [ABSTRACT FROM AUTHOR]

Introduction: Iron deficiency is the most common nutritional disorder worldwide. It is estimated to be present in 50-60% of chronic heart failure patients; contributing to a significant increase in the rate of hospitalisations and almost doubling mortality risk in these patients. Erythroferrone (ERFE) is a recently discovered protein involved in the regulation of iron, and its potential role as an iron regulatory biomarker in acute heart failure is unknown. Methods: Normal range levels of ERFE, iron and ferritin were determined from 155 healthy individuals. The clinical utility of ERFE was determined in 442 patient samples taken at the time of presentation to the emergency department with the primary complaint of breathlessness, suspicious of acute decompensated heart failure (ADHF). Samples were interrogated by specific assay for ERFE (ELISA, Intrinsic Lifesciences), NT-proBNP and hsTnT (Roche Cobas e411). Results: In the 155 healthy individuals (median age 47, IQR: 31-57, 49% female), the median value of ERFE was 0.51 ng/mL (IQR: 0.12-1.25). ERFE was significantly lower in women (0.32 vs 0.67 ng/mL, p=0.000) and did not correlate with ferritin (p=0.064) or iron (p=0.419). In the breathless cohort (n=442, median age 73, IQR: 62-81, 43% female), 35% of patients had adjudicated diagnosis of ADHF. ERFE levels were significantly elevated in ADHF (n=137, 5.1 ng/mL, IQR: 2.5-10.8) compared with non-ADHF patients (n=253, 1.6 ng/mL, IQR: 0.64-3.8), (p=0.011). The ability to diagnose ADHF was determined by ROC curves, with ERFE having an AUC of 0.746 (95% CI: 0.697-0.795, p<0.001) which was superior to hsTnT (AUC=0.732) but did not add to the performance of NT-proBNP (AUC=0.847). Logistic regression revealed ERFE to be a significant, independent predictor of ADHF (p=0.012), second only to NT-proBNP. When patients were stratified on the basis of hemoglobin levels above or below 129 g/L, ERFE was an independent predictor of ADHF in both groups (<129, p=0.039), (>129, p=0.040). Furthermore, in those below the NT-proBNP age dependent cut-off of 106 pmol/L (900 pg/mL, n=182 patients), only ERFE remained a significant, independent predictor of ADHF (p=0.009). Conclusion: These results suggest ERFE has merit as an iron related factor that may be relevant to acute and chronic heart failure. [ABSTRACT FROM AUTHOR]

The initiative for estimating glomerular filtration rate (GFR) derives from the limitations of interpreting plasma creatinine alone, the cost and complexities of determining a gold standard GFR with either inulin or radionuclides, and the inaccuracies inherent in measuring a 24 h urine creatinine clearance. In August 2005, the Australasian Creatinine Consensus Working Group recommended that an eGFR based on the abbreviated MDRD (Modification of Diet in Renal Disease) formula shall be automatically calculated for every request for creatinine in people over 18 years. Uptake was almost universal, though with appropriate caveats in place regarding potential limitations. Updated recommendations in 2007 recognised uniform standardisation of the plasma creatinine assay. A recent development is the CKD-Epidemiology Collaboration (CKD-EPI) equation which confers less underestimation of GFR in subjects with normal renal function. Cystatin C and its derivative equations may have advantages in some situations.