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.

Heart failure mortality according to acute variations in N-terminal pro B-type natriuretic peptide and cystatin C levels.

AIM: Changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cystatin C (CysC) are predictors of adverse outcomes in acute heart failure. This study assess whether NT-proBNP variations might provide independent information in addition to that obtained from CysC levels. METHODS: NT-proBNP levels were assessed in patients admitted due to acute heart failure using an observational study. Patients were classified as follows: group 1, those with a decrease in NT-proBNP levels of at least 30% from admission to 4 weeks after discharge; group 2, those with no significant changes in levels; and group 3, those who showed an increase in NT-proBNP of 30%. A multivariable Cox regression model and c-statistics were used. The primary end-point was all-cause mortality at 1-year follow-up. RESULTS: A total of 195 patients completed the follow-up. The mortality rate reached 20.5% (40 patients); 14 out of the 32 in group 3. The cumulative incidence of death, according to the change in NT-proBNP and Kaplan-Meier analysis, showed a significant increase in group 3 (log-rank P = 0.004). In the multivariable analysis, NT-proBNP variation for group 3 (hazard ratio 4.27; P <0.001) and for group 2 (hazard ratio 2.19; P = 0.043) in comparison with group 1 were independently associated with all-cause mortality, as well as anemia, hyponatremia, and admission CysC levels. Patients in group 3, and those with levels of serum CysC above the median, were also associated with slight increase in mortality. CONCLUSION: An increase of at least 30% in NT-proBNP levels after hospitalization is related to all-cause mortality in patients with acute heart failure and provides supplementary prognostic information in patients with high levels of CysC. A decrease in NT-proBNP of at least 30% is a desirable target to achieve.

Predictive value of serum galectin-3 levels in patients with acute heart failure with preserved ejection fraction.

AIMS: This study was conducted to determine whether galectin-3 (Gal3), a ß-galactoside-binding lectin, has usefulness to predict outcomes in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We measured Gal3, urea, creatinine and natriuretic peptides on admission in 419 selected patients with HF and LVEF over 45%. The primary endpoint was all-cause mortality and/or readmission at one-year follow-up. Multivariable Cox proportional hazards models were generated for Gal3 and classical risk factors. We also evaluated the reclassification of patients on the basis of the different score category after adding Gal3 levels. A total of 219 patients had combined adverse events, and 129 patients died during the follow-up. Kaplan-Meir survival curve showed significantly increased primary endpoint and all-cause mortality according to quartiles of Gal3 (log rank, P<0.001). Serum Gal3 levels above median (13.8 ng/ml) was a significant predictor of primary endpoint risk after adjustment for age, estimated glomerular filtration rate, anemia, diabetes, serum sodium, brain natriuretic peptide levels, NYHA class and urea, respectively (hazard ratio 1.43, 95% CI 1.07-1.91 P=0.015). The reclassification index increased significantly after addition of Gal3 (9.5%, P<0.001) and the integrated discrimination index was 0.022, (P=0.001). The clinical prediction model with Gal3 increased the c-statistic from 0.711 to 0.731 (difference of 0.020, P=0.001). CONCLUSIONS: Serum Gal3 is a strong and independent predictor of unfavorable outcomes in patients with HF and preserved LVEF. We also demonstrated the improvement of adding the new biomarker to the model.

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.

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.

Prognostic value of cystatin C on admission in heart failure with preserved ejection fraction.

BACKGROUND: Cystatin C has emerged as a new biomarker of renal function that has been found to predict adverse cardiovascular outcomes, especially heart failure (HF). Evidence of the usefulness of cystatin C in patients with heart failure with preserved ejection fraction (HFPEF) remains sparse. It is hypothesized that serum cystatin C levels in HFPEF has prognostic value. METHODS AND RESULTS: Cystatin C, urea nitrogen, creatinine, and N-terminal proBNP-type natriuretic peptide levels were measured on admission in 218 consecutive patients with HF and left ventricular ejection fraction >45%, as measured by Doppler echocardiography. The primary end point was all-cause mortality and/or readmission at 1 year. We determined the adjusted hazard ratio (HR) by Cox regression model. During the 1-year follow-up period, 70 patients (32.2%) died, and 126 patients (57.8%) died and/or required rehospitalization. Serum cystatin C levels by quartiles were associated with increased risk for adverse events. Kaplan-Meier survival curves showed significantly increased primary end point with each quartile of cystatin C (log rank <0.001). Patients in the highest quartile of cystatin C level were at increased adjusted risk for the primary end point (HR 3.40; 95% confidence interval [CI] 1.86-6.21; P < .0001) and all-cause mortality (HR 8.14; 95% CI 1.21-23.26; P < .01). Furthermore, high serum cystatin C levels were also associated with poor prognosis despite normal or mildly reduced renal function. CONCLUSIONS: Serum cystatin C level on admission in patients with HFPEF is a strong and independent predictor of an unfavorable outcome. This relationship remains in patients without advanced renal dysfunction.