Finding acute coronary syndrome with serial troponin testing for rapid assessment of cardiac ischemic symptoms (FAST-TRAC): a study protocol

Objective@#To determine the utility of a highly sensitive troponin assay when utilized in the emergency department. @*Methods@#The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician’s clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible.Trial registration ClinicalTrials.gov Identifier NCT00880802

Proenkephalin Predicts Organ Failure, Renal Replacement Therapy, and Mortality in Patients With Sepsis

Background@#Kidney failure occurs frequently and is associated with high mortality during sepsis. Proenkephalin (PENK) is an emerging biomarker of kidney function. We explored whether PENK levels could predict severity, organ failure, and mortality in septic patients. @*Methods@#We measured the PENK level in the plasma of 215 septic patients using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany). This was analyzed in terms of sepsis severity, vasopressor use, 30-day mortality, sequential organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD-EPI eGFR) categories, and renal replacement therapy (RRT) requirement. @*Results@#The PENK levels were significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (P = 0.02, P = 0.007, P < 0.001, respectively). The PENK levels were significantly associated with SOFA renal subscore and CKD-EPI eGFR categories (both P < 0.001). The distribution of lower eGFR ( < 60 mL/min/1.73 m2 ), RRT requirement, SOFA renal subscore, and the number of organ failures differed significantly according to the PENK quartile (P for trend < 0.001 or 0.017). The 30-day mortality rate also differed significantly according to the PENK quartile (P for trend < 0.001). @*Conclusions@#PENK could be an objective and reliable marker to predict severity, organ failure, and 30-day mortality in septic patients.

HDL Subclass Analysis in Predicting Metabolic Syndrome in Koreans With High HDL Cholesterol Levels

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is a complex mixture of subclasses with heterogeneous atheroprotective activities. We analyzed HDL-C subclass in relation to cardiovascular risk and metabolic syndrome (MetS) in a population with high HDL-C levels.METHODS: A total of 300 Korean individuals with high HDL-C levels (≥2.331 mmol/L) were enrolled following a comprehensive general medical examination including body composition analysis. HDL3-C levels were measured using the HDL3-EX SEIKEN kit (Randox Ltd., Crumlin, UK) and non-HDL3-C levels were calculated by subtracting HDL3-C levels from total HDL-C levels.RESULTS: HDL3-C levels and HDL3-C proportion had a weak positive correlation with low-density lipoprotein cholesterol (LDL-C) and triglycerides (r=0.21, r=0.25; r=0.26, r=0.34, respectively, all P<0.001); in contrast, non-HDL3-C levels had a weak negative correlation with these parameters (r=−0.17 and r=−0.25, respectively, both P<0.005). HDL3-C levels and HDL3-C proportion were significantly higher in the MetS group (N=8) than in the non-MetS group (0.71 vs 0.63 mmol/L, P=0.001; 29.7 vs 25.8%, P=0.001, respectively); these were the only predictors of MetS among the lipid variables (areas under the curves [AUC]=0.84 and 0.83, respectively, both P=0.001).CONCLUSIONS: In populations with high HDL-C levels, HDL-C subclass may provide a greater amount of information on cardiovascular risk and MetS than HDL-C levels alone.

Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis

BACKGROUND: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.

Comparison Between Soluble ST2 and High-Sensitivity Troponin I in Predicting Short-Term Mortality for Patients Presenting to the Emergency Department With Chest Pain

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. METHODS: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. RESULTS: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P35 ng/mL at ED arrival died during the 30-day follow-up. CONCLUSIONS: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality.

Soluble Suppression of Tumorigenicity 2 and Echocardiography in Sepsis

Soluble suppression of tumorigenicity 2 (sST2) has emerged as a biomarker of cardiac stretch or remodeling, and has demonstrated a role in acutely decompensated heart failure. However, its role in sepsis-induced cardiac dysfunction is still unknown. We explored whether sST2 serum concentration reflects either systolic or diastolic dysfunction as measured by Doppler echocardiography. In a total of 127 patients with sepsis, correlations between sST2 and blood pressure, left ventricular (LV) ejection fraction, LV diastolic filling (ratio of early transmitral flow velocity to early diastolic mitral annulus velocity), and resting pulmonary arterial pressure were evaluated. Correlations between sST2 and other sepsis biomarkers (high-sensitivity C-reactive protein [hs-CRP] and procalcitonin) were also examined. sST2 showed a moderate correlation with mean arterial pressure (r=-0.3499) but no correlation with LV ejection fraction, diastolic filling, or resting pulmonary hypertension. It showed moderate correlations with hs-CRP and procalcitonin (r=0.2608 and r=0.3829, respectively). sST2 might have a role as a biomarker of shock or inflammation, but it cannot reflect echocardiographic findings of LV ejection fraction or diastolic filling in sepsis.

Comparing Results of Five Glomerular Filtration Rate-Estimating Equations in the Korean General Population: MDRD Study, Revised Lund-Malmö, and Three CKD-EPI Equations

BACKGROUND: Estimated glomerular filtration rate (eGFR) is a widely used index of kidney function. Recently, new formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or the Lund-Malmö equation were introduced for assessing eGFR. We compared them with the Modification of Diet in Renal Disease (MDRD) Study equation in the Korean adult population. METHODS: The study population comprised 1,482 individuals (median age 51 [42-59] yr, 48.9% males) who received annual physical check-ups during the year 2014. Serum creatinine (Cr) and cystatin C (CysC) were measured. We conducted a retrospective analysis using five GFR estimating equations (MDRD Study, revised Lund-Malmö, and Cr and/or CysC-based CKD-EPI equations). Reduced GFR was defined as eGFR <60 mL/min/1.73 m2. RESULTS: For the GFR category distribution, large discrepancies were observed depending on the equation used; category G1 (≥90 mL/min/1.73 m2) ranged from 7.4-81.8%. Compared with the MDRD Study equation, the other four equations overestimated GFR, and CysC-based equations showed a greater difference (-31.3 for CKD-EPI(CysC) and -20.5 for CKD-EPI(Cr-CysC)). CysC-based equations decreased the prevalence of reduced GFR by one third (9.4% in the MDRD Study and 2.4% in CKD-EPI(CysC)). CONCLUSIONS: Our data shows that there are remarkable differences in eGFR assessment in the Korean population depending on the equation used, especially in normal or mildly decreased categories. Further prospective studies are necessary in various clinical settings.

Soluble ST2 Levels and Left Ventricular Structure and Function in Patients With Metabolic Syndrome

BACKGROUND: A biomarker that is of great interest in relation to adverse cardiovascular events is soluble ST2 (sST2), a member of the interleukin family. Considering that metabolic syndrome (MetS) is accompanied by a proinflammatory state, we aimed to assess the relationship between sST2 and left ventricular (LV) structure and function in patients with MetS. METHODS: A multicentric, cross-sectional study was conducted on180 MetS subjects with normal LV ejection fraction as determined by echocardiography. LV hypertrophy (LVH) was defined as an LV mass index greater than the gender-specific upper limit of normal as determined by echocardiography. LV diastolic dysfunction (DD) was assessed by pulse-wave and tissue Doppler imaging. sST2 was measured by using a quantitative monoclonal ELISA assay. RESULTS: LV mass index (β=0.337, P<0.001, linear regression) was independently associated with sST2 concentrations. Increased sST2 was associated with an increased likelihood of LVH [Exp (B)=2.20, P=0.048, logistic regression] and increased systolic blood pressure [Exp (B)=1.02, P=0.05, logistic regression]. Comparing mean sST2 concentrations (adjusted for age, body mass index, gender) between different LV remodeling patterns, we found the greatest sST2 level in the group with concentric hypertrophy. There were no differences in sST2 concentration between groups with and without LV DD. CONCLUSIONS: Increased sST2 concentration in patients with MetS was associated with a greater likelihood of exhibiting LVH. Our results suggest that inflammation could be one of the principal triggering mechanisms for LV remodeling in MetS.

Soluble ST2 Has a Prognostic Role in Patients With Suspected Sepsis

BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) has emerged as a novel biomarker for heart failure, and serum sST2 concentrations could be increased in inflammatory diseases. We explored whether sST2 is related to cardiac dysfunction/failure and has a prognostic role in patients with suspected sepsis. METHODS: In a total of 397 patients with suspected sepsis, sST2 concentrations were measured by using the Presage ST2 Assay (Critical Diagnostics, USA). sST2 concentrations were analyzed according to procalcitonin (PCT) concentrations, cardiovascular subscores of the sepsis-related organ failure assessment (SOFA) score, and clinical outcomes. RESULTS: sST2 concentrations were increased significantly according to the five groups of PCT concentrations and cardiovascular subscores of the SOFA score (P<0.000001 and P=0.036, respectively). In-hospital mortality was significantly higher among patients with sST2 concentrations above 35 ng/mL (P=0.0213) and among patients with increased concentrations of both sST2 and PCT (P=0.0028). CONCLUSIONS: sST2 seems to be related to both cardiac dysfunction/failure and severity in sepsis. Measurement of sST2 and PCT in combination would be useful for risk stratification and prognosis prediction in patients with suspected sepsis.