Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study.

AIMS: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. METHODS AND RESULTS: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk. CONCLUSION: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Effect of concomitant antiplatelet therapy in patients with nonvalvular atrial fibrillation initiating non-vitamin K antagonists.

BACKGROUND: Antiplatelet therapy (APT) use in combination with oral anticoagulation is common among patients with atrial fibrillation, but there is scarce information regarding its effect on outcomes in patients on non-vitamin K antagonist oral anticoagulants (NOAC). We aimed to evaluate the safety and efficacy of APT use in a 'real-world' cohort of nonvalvular atrial fibrillation (NVAF) patients initiating NOAC. DESIGN: We conducted a retrospective multicentre study including 2361 consecutive NVAF patients initiating NOAC between January 2013 and December 2016. Patients with an acute ischaemic event within the last 12 months (acute coronary syndrome, stroke or revascularization) were excluded. Patients were followed up, and all clinical events were recorded at 3 months. The primary outcome of the study was major bleeding, and the secondary outcomes were stroke, nonfatal myocardial infarction, intracranial bleeding and death. RESULTS: One hundred forty-five (6.1%) patients received concomitant APT, and aspirin was the more common (79%). At 3 months, 25 (1.1%) patients had major bleeding, 8 (0.3%) had nonfatal myocardial infarction, 7 (0.3%) had ischaemic stroke, and 40 (1.7%) died. After multivariate adjustment, concomitant APT was associated with higher risk for major bleeding (HR = 3.62, 95% CI 1.32-9.89; P = .012), but was not associated with a higher risk of other clinical outcomes. CONCLUSIONS: Concomitant APT use is uncommon among these patients and does not seem to be associated with lower rates of ischaemic events or death. However, there are signals for an increased risk of bleeding, which reinforces current guideline recommendations.

Effectiveness and safety of rivaroxaban in a cohort of 142 patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke.

AIM: To evaluate the clinical profile and effectiveness/safety of patients taking rivaroxaban in clinical practice. METHODS: Retrospective study that included patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke between January 2012 and December 2016 in a tertiary hospital in Spain. RESULTS: A total of 142 patients (median age 78 years, 40.1% men, 32.4% creatinine clearance <50 ml/min; 96.5% CHA2DS2-VASc ≥2; 44.3% HAS-BLED ≥3) were included. Only two patients had a thromboembolic event (in both cases ischemic stroke) and three patients had major bleeding (rates of 1.3 and 1.9 events/100 patient years, respectively). CONCLUSION: Data regarding effectiveness and safety in our cohort were consistent with previous studies, showing that rivaroxaban can be effective and safely used in our setting.

Association Between Ischemic and Bleeding Risk Scores and the Use of New P2Y12 Inhibitors in Patients With Acute Coronary Syndrome.

INTRODUCTION AND OBJECTIVES: Acute coronary syndrome (ACS) guidelines recommend the use of newer P2Y12 inhibitors (prasugrel and ticagrelor) over clopidogrel in patients with moderate-to-high ischemic risk, unless they have an increased bleeding risk. The aim of our study was to assess the GRACE risk score and the CRUSADE bleeding risk score relative to prescription of newer P2Y12 inhibitors at discharge in ACS patients. METHODS: Retrospective analysis of a multicenter ACS registry; 3515 consecutive patients were included. The association between risk scores and prescription of newer P2Y12 inhibitors was assessed by binary logistic regression analysis. RESULTS: A total of 1021 patients (29%) were treated with prasugrel or ticagrelor. On multivariate analyses, both GRACE (OR per 10 points, 0.89; 95%CI, 0.86-0.92; P < .001) and CRUSADE (OR per 10 points, 0.96; 95%CI, 0.94-0.98; P < .001) risk scores were inversely associated with the use of newer P2Y12 inhibitors. Moreover, other factors not included in these scores (revascularization approach, in-hospital stent thrombosis, major bleeding, and concomitant indication for anticoagulation therapy) also predicted the use of newer P2Y12 inhibitors. CONCLUSIONS: New P2Y12 inhibitors were more frequently prescribed among ACS patients with lower CRUSADE bleeding risk. However, an ischemic risk paradox was found, with higher use of these agents in patients with lower ischemic risk based on GRACE risk score estimates. These results underscore the importance of risk stratification to safely deliver optimal therapies.

Comparison of Risk Prediction With the CKD-EPI and MDRD Equations in Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (GFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. HYPOTHESIS: New CKD-EPI equations improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and provide complementary information to the Global Registry of Acute Coronary Events (GRACE) risk score. METHODS: We studied 350 subjects (mean age, 68 ± 12 years; 70% male) with NSTE-ACS. Estimated GFR was calculated using the MDRD and new CKD-EPI equations based on serum creatinine (SCr) and/or cystatin C (CysC) concentrations obtained within 48 hours of hospital admission. The primary endpoint was all-cause death during follow-up. RESULTS: Over the study period (median, 648 days [interquartile range, 236-1042 days]), 31 patients died (0.05% events per person-year). Decedents had poorer renal-function parameters (P < 0.001). Both CysC-based CKD-EPI equations had the highest areas under the receiver operating characteristic curve for the prediction of all-cause mortality. After multivariate adjustment, only CysC-based CKD-EPI equations were independent predictors of all-cause mortality (CKD-EPISCr - CysC , per mL/min/1.73 m(2) : hazard ratio: 0.975, 95% confidence interval: 0.956-0.994, P = 0.009; CKD-EPICysC , per mL/min/1.73 m(2) : hazard ratio: 0.976, 95% confidence interval: 0.959-0.993, P = 0.005). Reclassification analyses showed that only CysC-based CKD-EPI equations improved predictive accuracy of the GRACE risk score. CONCLUSIONS: In patients with NSTE-ACS, CysC-based CKD-EPI equations improved clinical risk stratification for mortality and added complementary prognostic information to the GRACE risk score.

Comparison between type-2 and type-1 myocardial infarction: clinical features, treatment strategies and outcomes.

OBJECTIVE: To assess the differences in incidence, clinical features, current treatment strategies and outcome in patients with type-2 vs. type-1 acute myocardial infarction (AMI). METHODS: We included 824 consecutive patients with a diagnosis of type-1 or type-2 AMI. During index hospitalization, clinical features and treatment strategies were collected in detail. At 1-year follow-up, mortality, stroke, non-fatal myocardial infarction and major bleeding were recorded. RESULTS: Type-1 AMI was present in 707 (86%) of the cases while 117 (14%) were classified as type-2. Patients with type-2 AMI were more frequently female and had higher co-morbidities such as diabetes, previous non-ST segment elevation acute coronary syndromes, impaired renal function, anaemia, atrial fibrillation and malignancy. However, preserved left ventricular ejection fraction and normal coronary arteries were more frequently seen, an invasive treatment was less common, and anti-platelet medications, statins and beta-blockers were less prescribed in patients with type-2 AMI. At 1-year follow-up, type-2 AMI was associated with a higher crude mortality risk (HR: 1.75, 95% CI: 1.14-2.68; P = 0.001), but this association did not remain significant after multivariable adjustment (P = 0.785). Furthermore, we did not find type-2 AMI to be associated with other clinical outcomes. CONCLUSIONS: In this real-life population, compared with type-1, type-2 AMI were predominantly women and had more co-morbidities. Invasive treatment strategies and cardioprotective medications were less used in type-2, while the 1-year clinical outcomes were similar.

sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with high morbidity and mortality, even despite the use of oral anticoagulation (OAC). Soluble suppression of tumorigenicity-2 (sST2) is a member of the interleukin-1 receptor family [interleukin-1 receptor-like 1 (IL1RL1)], which has been associated with an increased risk of mortality and morbidity in heart failure or acute coronary syndrome. We assessed the predictive value of sST2 levels in an unselected 'real-world' cohort of anticoagulated AF patients. METHODS: We included 562 patients (49% male; median age 77 [IQR: 71-82]) with permanent AF who were stable (for at least 6 months) on OAC (INRs 2.0-3.0). sST2 levels were quantified by ELISA. Patients were followed-up for up to 4 years, and cardiovascular events and all-cause mortality were recorded. RESULTS: Median (IQR) of sST2 levels was 51.23 (39.09-67.40) µg/L. Median follow-up was 1587 days [IQR 1482-1617], and during this period, 91 patients died (16.2%, 3.72%/year). The c-statistic for predicting mortality with sST2 was 0.58 + 0.03; P = 0.017). On multivariate analysis, age [hazard ratio (HR) 1.09 (1.05-1.13); P < 0.001], diabetes mellitus [1.76 (1.08-2.88); P = 0.023], previous stroke [2.16 (1.29-3.60); P = 0.003] and sST2 levels [1.008 (1.002-1.14); P = 0.008] were independently associated with mortality. Concentrations of sST2 were also significantly associated with the risk of mortality, even after adjusting for the CHA2 DS2 -VASc score [HR: 1.007 (1.001-1.013); P = 0.014]. CONCLUSIONS: In an anticoagulated AF patient's cohort, sST2 levels are an independent predictive factor of all-cause mortality. sST2 levels could be a biomarker used to improve clinical risk assessment in anticoagulated AF patients.

Cystatin C-based CKD-EPI equations and N-terminal pro-B-type natriuretic peptide for predicting outcomes in acutely decompensated heart failure.

BACKGROUND: In patients with acute decompensated heart failure (ADHF), both natriuretic peptides and renal impairment predict adverse outcomes. Our aim was to evaluate the complementary prognosis role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on cystatin C (CysC) for glomerular filtration rate (GFR) estimation in ADHF patients. HYPOTHESIS: Renal impairment assessed by CysC-based CKD-EPI equations and natriuretic peptides have complementary prognostic value in ADHF patients. METHODS: The study included 613 consecutive patients presenting with ADHF. At admission, plasma levels of NT-proBNP and CysC were determined. The GFR was estimated using CysC-based CKD-EPI equations. The primary endpoint was death from any cause and heart failure readmission. RESULTS: During the median follow-up of 365 days (interquartile range, 227-441 days), 323 patients (0.65 %patient-year) died or were readmitted for heart failure. After multivariate adjustment, estimated GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL were independent predictors of adverse outcomes (P < 0.01). The combination of GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL was associated with the highest risk of adverse outcomes. Furthermore, reclassification analyses demonstrated that use of both NT-proBNP and CysC-based CKD-EPI equations resulted in improving the accuracy for adverse outcomes prediction. CONCLUSIONS: In patients with ADHF, the combination of NT-proBNP with estimated GFR using CysC-based CKD-EPI equations better predicts outcomes than either parameter alone and adds valuable complementary prognosis information to other established risk factors.

Major bleeding risk prediction using Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations in acute coronary syndrome.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). MATERIALS AND METHODS: Three hundred and fifty consecutive subjects with non-ST-segment elevation ACS (68 ± 12 years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. RESULTS: During the median follow-up of 589 days (interquartile range, 390-986), 27 patients had MB (0.04% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P < 0.001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPI(creatinine-cystatin) C per mL/min/1.73 m(2), HR = 0.973 (95%CI 0.955-0.991; P = 0.003) and CKD-EPI(cystatin) C per mL/min/1.73 m(2), HR = 0.976 (95%CI 0.976-0.992; P = 0.003), while the CKD-EPI(creatinine) and MDRD equations did not achieve statistical significance. Both CKD-EPI(creatine-cystatin) C and CKD-EPI(cystatin) C were associated with a significant improvement in MB risk reclassification. CONCLUSIONS: In this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application.

Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation.

There are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation.We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2-VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09-2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2-VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2-VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65 % increase in miR-146a-5p levels, while TT individuals only showed a 28 % increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52 % vs 26 %). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p.

Comparison of risk prediction with the CKD-EPI and MDRD equations in acute decompensated heart failure.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively). CONCLUSIONS: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification.

Beta-trace protein and cystatin c as predictors of major bleeding in non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. We assessed the ability of both to predict major bleeding (MB) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), compared to other renal function parameters and clinical risk scores. METHODS AND RESULTS: We included 273 patients. Blood samples were obtained within 24h of admission. The endpoint was MB. During a follow-up of 760 days (411-1,098 days), 25 patients (9.2%) had MB. Patients with MB had higher concentrations of BTP (0.98 mg/L; 0.71-1.16 mg/L vs. 0.72 mg/L, 0.60-0.91 mg/L, P=0.002), CysC (1.05 mg/L; 0.91-1.30 mg/L vs. 0.90 mg/L, 0.75-1.08 mg/L, P=0.003), higher CRUSADE score (39 ± 16 points vs. 29 ± 15 points, P=0.002) and lower estimated glomerular filtration rate (eGFR; 66 ± 27 vs. 80 ± 30 ml·min(-1)·1.73 m(-2), P=0.02) than patients without MB; there was no difference in creatinine level between the groups (P=0.14). After multivariable adjustment, both were predictors of MB, while eGFR and creatinine did not achieve statistical significance. Among subjects with eGFR >60 ml·min(-1)·1.73 m(-2), those with elevated concentrations of both biomarkers had a significantly higher risk for MB. Net reclassification indexes from the addition of BTP and CysC to CRUSADE risk score were 38% and 21% respectively, while the relative integrated discrimination indexes were 12.5% and 3.8%. CONCLUSIONS: Among NSTE-ACS patients, BTP and CysC were superior to conventional renal parameters for predicting MB, and improved clinical stratification for hemorrhagic risk.

ß-Trace protein: from GFR marker to cardiovascular risk predictor.

ß-Trace protein, also known as Lipocalin type prostaglandin D synthase, is a low-molecular mass glycoprotein (between 23,000 and 29,000 Da depending on the degree of glycosylation) that converts prostaglandin H2 into prostaglandin D2. ß-Trace protein was initially isolated from cerebrospinal fluid and served as a marker of cerebrospinal fluid leakage; however, its cDNA and gene have been isolated in numerous human body tissues, including central nervous system, retina, melanocytes, heart, and male genital organs. In recent years, ß-trace protein has emerged as a promising novel endogenous marker of GFR, representing a more sensitive marker for mild kidney dysfunction than serum creatinine. In this regard, ß-trace protein has been proposed as an alternative marker to Cystatin C for measuring kidney function. Beyond its role for estimating renal function, ß-trace protein is also emerging as a novel biomarker in cardiovascular risk. It has been associated with several cardiovascular disorders, playing a potential role for prognostic stratification in patients with acutely decompensated heart failure and acute coronary syndromes and being advocated as a novel marker for cardiovascular risk prediction.

Interleukin-6 and high-sensitivity C-reactive protein for the prediction of outcomes in non-ST-segment elevation acute coronary syndromes.

INTRODUCTION AND OBJECTIVES: High baseline levels of interleukin-6 and C-reactive protein confer an increased risk of mortality in non-ST-segment elevation acute coronary syndrome. The aim of the study was to determine whether serial measurements of interleukin-6 and high-sensitivity C-reactive protein provide additional information to baseline measurements for risk stratification of non-ST-segment elevation acute coronary syndrome. METHODS: Two hundred and sixteen consecutive patients with non-ST-segment elevation acute coronary syndrome were prospectively included. Blood samples were obtained within 24 h of hospital admission and at 30 days of follow-up. The endpoint was a composite of all-cause death, nonfatal myocardial infarction, or acute decompensated heart failure. RESULTS: Both interleukin-6 and high-sensitivity C-reactive protein levels decreased from day 1 to day 30, regardless of adverse events (both P<.001). Interleukin-6 levels at 2 time points (interleukin-6 day 1, per pg/mL; hazard ratio=1.006, 95% confidence interval, 1.002-1.010; P=.002 and interleukin-6 day 30, per pg/mL, hazard ratio=1.047, 95% confidence interval, 1.021-1.075, P<.001) were independent predictors of adverse events, whereas high-sensitivity C-reactive protein day 1 and high-sensitivity C-reactive protein day 30 levels were not. Patients with interleukin-6 day 1≤8.24 pg/mL and interleukin-6 day 30≤4.45 pg/mL had the lowest event rates (4.7%), whereas those with both above the median values had the highest event rates (35%). After addition of interleukin-6 day 30 to the multivariate model, C-index increased from 0.71 (95% confidence interval, 0.63-0.78) to 0.80 (95% confidence interval, 0.72-0.86), P=.042, and net reclassification improvement was 0.39 (95% confidence interval, 0.14-0.64; P=.002). CONCLUSIONS: In this population, both interleukin-6 and high-sensitivity C-reactive protein concentrations decreased after the acute phase. Serial samples of interleukin-6 concentrations improved the prognostic risk stratification of these patients.

Prognostic value of serum cystatin C and N-terminal pro b-type natriuretic peptide in patients with acute heart failure.

BACKGROUND: Cystatin C (CysC) is a good prognostic marker in heart failure. However, there is not much information of CysC combined with other biomarkers in acute heart failure (AHF). AIM: To assess prognostic value of CysC and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients hospitalized for AHF with no apparent deterioration of renal function. DESIGN: Prospective, multicenter, observational study. METHODS: CysC and NTpro-BNP were measured in patients consecutively admitted with a diagnosis of AHF. Patients with, NTpro-BNP concentration above 900 pg/mL and serum creatinine below 1.3mg/dL, were included for statistical analysis. End-point of the study was all-cause mortality during a 12-month follow-up. RESULTS: 526 patients with AHF and NTpro-BNP concentration above 900 pg/mL were included in the study. From this group, 367 patients (69.8%) had serum creatinine below 1.3mg/dL. Receiver operating characteristic (ROC) curves were used to determine the best cut-off value for CysC. Patients with a concentration of CsyC above 1.25mg/dL had a 37.8% mortality rate, vs. 13.6% for those below cut-off (p<0.001). After Cox proportional hazard model, age, CysC, low total cholesterol and HF with preserved ejection fraction remained significantly associated with all-cause mortality during one-year follow-up. CONCLUSIONS: In AHF and normal or slightly impaired renal function, performance of CysC may be superior to NT-proBNP. Hence, CysC may be the preferred biomarker in the assessment of patients with AHF and slightly impaired renal function.

Usefulness of ß-trace protein and cystatin C for the prediction of mortality in non ST segment elevation acute coronary syndromes.

Beta-trace protein (BTP) is a low-molecular mass protein belonging to the lipocalin protein family, which is more sensitive than serum creatinine for detecting impaired renal function. The aims of the present study were to evaluate whether plasma BTP improves the risk stratification of patients with non-ST-segment elevation acute coronary syndromes and to compare it to cystatin C (CysC), serum creatinine, and estimated glomerular filtration rate. Two hundred twenty-six consecutive patients with non-ST-segment elevation acute coronary syndromes were prospectively included. Blood samples were obtained within 24 hours of hospital admission to measure BTP, CysC, and creatinine. The study end point was all-cause death. Over a median follow-up period of 859 days (interquartile range [IQR] 524 to 1,164), 24 patients (10.6%) died. Decedents had higher concentrations of BTP (1.03 mg/L [IQR 0.89 to 1.43] vs 0.74 mg/L [IQR 0.61 to 0.92], p <0.001), CysC (1.16 mg/L [IQR 0.91 to 1.59] vs 0.90 mg/L [IQR 0.76 to 1.08], p = 0.001), and serum creatinine (1.10 mg/L [IQR 0.87 to 1.46] vs 0.94 mg/L [IQR 0.80 to 1.10], p = 0.004) and a lower mean estimated glomerular filtration rate (60 ± 20 vs 80 ± 24 ml/min/1.73 m(2), p <0.001). After multivariate adjustment, BTP and CysC were predictors of all-cause death, while estimated glomerular filtration rate and serum creatinine concentrations did not achieve statistical significance. In stratified analyses according to kidney function, elevated BTP and CysC were associated with a higher risk for all-cause death. Reclassification analyses showed that BTP and CysC added complementary information to Global Registry for Acute Coronary Events (GRACE) risk score. In conclusion, BTP and CysC levels were associated with all-cause death risk and modestly improved prognostic discrimination beyond the GRACE risk score in patients with non-ST segment elevation acute coronary syndromes.

ß-trace protein and cystatin C as predictors of long-term outcomes in patients with acute heart failure.

OBJECTIVES: The purpose of this study was to evaluate the prognostic importance of novel markers of renal dysfunction among patients with acutely destabilized heart failure (ADHF). BACKGROUND: ß-trace protein (BTP) and cystatin C are newer biomarkers for renal dysfunction; the prognostic importance of these tests, particularly BTP, relative to standard measures of renal function remains unclear. METHODS: A total of 220 consecutive hospitalized patients with ADHF were prospectively studied. Blood samples were collected on presentation. In-hospital worsening renal function, as well as mortality and/or heart failure (HF) hospitalization, over a median follow-up period of 500 days was examined as a function of BTP or cystatin C concentrations; results were compared with creatinine, estimated glomerular filtration rate, and blood urea nitrogen. RESULTS: Neither BTP nor cystatin C was associated with worsening renal function during the index hospitalization. A total of 116 patients (53%) either died or were hospitalized for HF during follow-up. Those with adverse outcomes had higher BTP (1.04 mg/l [range 0.80 to 1.49 mg/l] vs. 0.88 mg/l [range 0.68 to 1.17 mg/l], p = 0.003) and cystatin C (1.29 mg/l [range 1.00 to 1.71 mg/l] vs. 1.03 mg/l [range 0.86 to 1.43 mg/l], p = 0.001). After multivariable adjustment, both BTP (hazard ratio: 1.41, 95% confidence interval: 1.06 to 1.88; p = 0.018) and cystatin C (hazard ratio: 1.50, 95% confidence interval: 1.13 to 2.01; p = 0.006) were significant predictors of death/HF hospitalization, whereas serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen were no longer significant. In patients with an estimated glomerular filtration rate >60 ml/min/1.73 m(2), elevated concentrations of BTP and cystatin C were still associated with significantly higher risk of adverse clinical events (p < 0.05). Net reclassification index analysis suggested cystatin C and BTP deliver comparable information regarding prognosis. CONCLUSIONS: Among patients hospitalized with ADHF, BTP and cystatin C predict risk of death and/or HF hospitalization and are superior to standard measures of renal function for this indication.