High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease.

BACKGROUND: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. OBJECTIVE: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. METHODS: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomarkers Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid-Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90mL/min/1.73m(2). RESULTS: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a GFR of 15mL/min/1.73m(2) varied from 2-fold to 15-fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured GFR and increased more at low GFR compared to hs-cTnI. For hFABP and NTproBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations). CONCLUSION: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations.

Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction.

BACKGROUND: Due to increasing co-morbidity associated with aging, heart failure (HF) has become more prevalent and heterogeneous in older individuals, and non-cardiovascular (CV) mortality has increased. Previously, we defined a multi-marker modality that included cystatin C (CysC), troponin T (TnT), and age. Here, we validated this multi-marker risk score by evaluating its predictions of all-cause mortality and CV mortality in an independent population of older individuals with HF and reduced ejection fraction (HFrEF). METHODS: This prospective cohort study included 124 patients, median age 73 years, that had HFrEF. We determined all-cause mortality and CV mortality at a 3-year follow-up. We compared the risk score to the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) for predicting all-cause mortality and CV mortality. RESULTS: High risk scores were associated with both all-cause mortality (HR 4.2, 95% CI 2.2-8.1, p < 0.001) and CV mortality (HR 3.6, 95% CI 1.7-8.0, p = 0.0015). Receiver operating characteristics showed similar efficacy for the risk score and NT-proBNP in predicting all-cause mortality (HR 0.74, 95% CI 0.65-0.81 vs. HR 0.74, 95% CI 0.65-0.81, p = 0.99) and CV mortality (HR 0.68, 95% CI 0.59-0.76 vs. HR 0.67, 95% CI 0.58-0.75, p = 0.95). When the risk score was added to the NT-proBNP, the continuous net reclassification improvement was 56% for predicting all-cause mortality (95% CI 18-95%, p = 0.004) and 45% for predicting CV mortality (95% CI 2-89%, p = 0.040). CONCLUSIONS: In HFrEF, a risk score that included age, TnT, and CysC showed efficacy similar to the NT-proBNP for predicting all-cause mortality and CV mortality in an older population.

Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study.

OBJECTIVE: Primarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF). DESIGN: Prospective cohort study. SETTING: Secondary care. Single centre. PATIENTS AND BIOMARKERS: 131 patients, aged ≥65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge. PRIMARY OUTCOME MEASURE: 3-year mortality. RESULTS: Mean age was 73±11 years; mean left ventricular ejection fraction , 43±14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000-8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000-8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000-8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively. CONCLUSIONS: Our results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.

Cystatin C in a composite risk score for mortality in patients with infective endocarditis: a cohort study.

OBJECTIVE: To develop a multimarker prognostic score for infective endocarditis (IE). DESIGN: Retrospective case-control. SETTING: Secondary care. Single centre. PARTICIPANTS: 125 patients with definite IE. PRIMARY OUTCOME MEASURES: 90-day and 5-year mortality. RESULTS: Mean age was 62.7±17 years. The 90-day and 5-year mortality was 10.4% and 33.6%, respectively. CysC levels at admission and over 20% increases in CysC levels during 2 weeks of treatment were prognostic for 90-day and 5-year mortality independent of creatinine estimated glomerular filtration rate. In multivariate analyses, CysC (OR 5.42, 95% CI 1.90 to 15.5, p=0.002) and age (OR 1.06, 95% CI 1.02 to 1.10, p=0.002) remained prognostic for 5-year mortality. NT-proBNP, TnT, C reactive protein and interleukin 6 were also linked to prognosis. A composite risk scoring system using levels of CysC, NT-proBNP, age and presence of mitral valve insufficiency was able to separate a high-risk and a low-risk group. CONCLUSIONS: CysC levels at admission and increase in CysC after 2 weeks of treatment were independent prognostic markers for both 90-day and 5-year mortality in patients with IE. A multimarker composite risk scoring system including CysC identified a high-risk group.

Prognostic values of NTpro BNP/BNP ratio in comparison with NTpro BNP or BNP alone in elderly patients with chronic heart failure in a 2-year follow up.

BACKGROUND: Plasma BNP and NT-proBNP are often used as interchangeable parameters in heart failure care in clinical practice. In our previous study we have shown that inflammation was able to induce increased NT pro BNP in a hospital cohort with chronic heart failure in the elderly, indicating that NT-proBNP/BNP ratio should be evaluated concomitantly with inflammatory status to avoid overestimation of heart failure severity. The present study was aimed to evaluate the clinical significance of NT-proBNP/BNP ratio in comparison with NTpro BNP or BNP alone as a prognostic indicator in a 2-year follow up of elderly heart failure population. MATERIALS AND METHODS: One hundred and eight-nine elderly heart failure patients (72 ± 11 years, male 52%, LVEF 46 ± 14%) were enrolled consecutively during 2006 and 2007 and followed up during 2 years. NTpro BNP and BNP were measured routinely. RESULTS: We have found that NTpro BNP/BNP ratio provides no additional prognostic information during follow up as compared to NTpro BNP or BNP alone in an elderly population with chronic heart failure. By the use of ROC curves, for total mortality predictive accuracy during 2 years, the cut-off values are NTproBNP ≥ 800 pg/ml, BNP > 60 pg/ml and NTpro BNP/BNP ratio>6.4 respectively. In terms of NTpro BNP, as long as its serum level is above 2000 pg/ml it indicates poor prognosis. However there is an overlap between serum concentration range 2000-8000 pg/ml and >8000 pg/ml in terms of prognostic indicator. Similarly for BNP, as long as its serum level is above 100 pg/ml, it indicates poor prognosis. However there is an overlap between serum concentration range 100-800 pg/ml and >800 pg/ml in terms of prognostic indicator. There was significant correlation between survival and NTpro BNP, BNP and Cystatin-C but not with NTpro BNP/BNP ratio. Such correlation exists irrespective of subgroups regardless of less than or older than 70 years old. CONCLUSIONS: Our results demonstrated that in elderly heart failure population NTpro BNP/BNP ratio may provide diagnostic help in the presence of acute infection but no additional prognostic information in the long run as compared with NTpro BNP or BNP alone. Furthermore, both NTpro BNP and BNP are useful prognostic biomarkers indeed but they need to be interpreted with caution when it is used as a single biomarker and in the meantime concomitant diseases exist because patients may die due to non-cardiac causes.