Background and Aims : Elevated concentrations of lipoprotein(a) (Lp(a)) are directly related to an increased risk of cardiovascular diseases, thus making its determination a crucial factor for clinical diagnosis. However, the lack of global standardisation of current immunoassay-based measuring procedures (MPs) for Lp(a) leads to inconsistent care of patients. The former Lp(a) reference method and the associated WHO-IFCC reference material are no longer available. Recently, it was decided to evolve to a next generation reference measurement system (RMS) with SI-traceability. To accomplish this an IFCC working group on quantitating apolipoproteins by mass spectrometry (MS) was formed. The SI-traceable RMS will consist of a MS-based, peptide-calibrated candidate reference measurement procedure (cRMP) and secondary serum-based reference materials (RMs) certified for their apolipoprotein(a) molar concentration.Methods: A correlation study was performed between the cRMP and immunoassay-based MPs using a panel of 39 clinical samples (CS) that cover the whole Lp(a) concentration range. In addition, the commutability of 14 different candidate RMs was investigated to select a suitable RM format for the future development of the serum-based RM.Results: Comparison of immunoassay-based MPs with the cRMP for measurements of CS in nmol/L demonstrated a good linear correlation, but showed significant measurement bias and sample specific differences.Conclusions: The results of the commutability study show that RMs based on human serum pools with endogenous Lp(a) are good candidates for future matrix-based certified RM, whereas human pools -spiked with recombinant apo(a) show different behaviour compared to CS, making them unsuitable as RMs in most of the currently available routine assays. Background and Aims : Elevated concentrations of lipoprotein(a) (Lp(a)) are directly related to an increased risk of cardiovascular diseases, thus making its determination a crucial factor for clinical diagnosis. However, the lack of global standardisation of current immunoassay-based measuring procedures (MPs) for Lp(a) leads to inconsistent care of patients. The former Lp(a) reference method and the associated WHO-IFCC reference material are no longer available. Recently, it was decided to evolve to a next generation reference measurement system (RMS) with SI-traceability. To accomplish this an IFCC working group on quantitating apolipoproteins by mass spectrometry (MS) was formed. The SI-traceable RMS will consist of a MS-based, peptide-calibrated candidate reference measurement procedure (cRMP) and secondary serum-based reference materials (RMs) certified for their apolipoprotein(a) molar concentration. Methods: A correlation study was performed between the cRMP and immunoassay-based MPs using a panel of 39 clinical samples (CS) that cover the whole Lp(a) concentration range. In addition, the commutability of 14 different candidate RMs was investigated to select a suitable RM format for the future development of the serum-based RM. Results: Comparison of immunoassay-based MPs with the cRMP for measurements of CS in nmol/L demonstrated a good linear correlation, but showed significant measurement bias and sample specific differences. Conclusions: The results of the commutability study show that RMs based on human serum pools with endogenous Lp(a) are good candidates for future matrix-based certified RM, whereas human pools -spiked with recombinant apo(a) show different behaviour compared to CS, making them unsuitable as RMs in most of the currently available routine assays.

Abstract Background The aim of our study was to evaluate the long-term prognostic value of blood-based biomarkers in comparison to the established National Institute of Health stroke scale (NIHSS) score in patients with acute ischemic stroke. Methods We measured plasma concentrations of IL-6, NT-proBNP, D-dimer, hs-cTnT, sST2, MR-proADM, MR-proANP, CT-proET-1, Copeptin, and Procalcitonin in 721 consecutive acute ischemic stroke patients within 24 h after admission to our stroke unit. Endpoint was all-cause mortality at 3 years. Results During follow-up, 199 patients died (28%). In univariate Cox proportional hazards regression analyses using a dichotomized approach according to median values, all blood-based biomarkers were associated with prognosis. However, in the multivariate analysis after adjustment for several clinical variables, only IL-6 >7 pg/mL (risk ratio, 3.00; 95% CI, 2.03–4.44; P<0.001), NT-proBNP >447 ng/L (risk ratio, 2.67; 95% CI, 1.81–3.92; P<0.001), NIHSS score >3 (risk ratio, 2.24; 95% CI, 1.63–3.07; P<0.001), Copeptin >13 pmol/L (risk ratio, 1.87; 95% CI, 1.34–2.61; P<0.001), and hs-cTnT >14 ng/L (risk ratio, 1.74; 95% CI, 1.21–2.49; P=0.001) remained independent predictors. ROC curve analysis for mortality prediction demonstrated a higher area under the curve (AUC) for IL-6 and NT-proBNP, respectively, when compared to the NIHSS score (IL-6 AUC 0.81 vs. NIHSS AUC 0.75; P=0.016 and NT-proBNP AUC 0.80 vs. NIHSS AUC 0.75; P=0.039) and similar AUCs when comparing the NIHSS with hs-TnT (hs-TnT AUC 0.77) and Copeptin (Copeptin AUC 0.72). Conclusions In this large cohort of patients with acute ischemic stroke the blood-based biomarkers IL-6, NT-proBNP, hs-cTnT, and Copeptin were strong and independent prognostic markers for 3-year all-cause mortality. IL-6 and NT-proBNP even outperformed the NIHSS score for long-term mortality prediction. ROC plots for 3-year all-cause mortality Funding Acknowledgement Type of funding source: None

Edoxaban is the most recent available representative of the Non-Vitamin K antagonist oral anticoagulants (NOAC). In the first part of an expert consensus document, we summarized the evidence derived from phase III trials of edoxaban for stroke prevention in patients with non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. This second part covers relevant aspects related to the use of edoxaban in everyday clinical practice, including initiation of therapy, switching, peri-operative strategies, follow-up schemes and handling of dosing errors. Further, coagulation measurement, clinically relevant drug interactions, indications for concomitant antiplatelet therapy, management of bleeding complications, and cardioversion are addressed.

Objectives: We aimed at evaluating the risk of all-cause mortality in PAD patients during a 10-year follow-up period and determining predictors of death at 10 years. We hypothesized that the predictors of death would be different in diabetic vs. non-diabetic PAD patients.

Objective: Atherosclerotic peripheral arterial disease (PAD) is one of the most prevalent, morbid, and mortal diseases. The aim of this study was to evaluate mortality rates of patients with atherosclerotic PAD stratified according to age and diabetes and to determine predictors of death.Methods: We studied 487 patients with symptomatic PAD consecutively admitted to the hospital. This cohort included the following four patient subgroups: (1) 216 patients with PAD <75 years of age without diabetes mellitus; (2) 115 patients with PAD <75 years of age with diabetes mellitus; (3) 102 patients with PAD >= 75 years of age without diabetes mellitus; and (4) 54 patients with PAD >= 75 years of age with diabetes mellitus. Control subjects without atherosclerotic disease were matched to the patients with PAD in a 1:1 design by sex, age (+/- 2 years), and diabetes mellitus status. Outcome measure was all-cause mortality at 5 years.Results: Mortality rates at 5 years were 10% in nondiabetic patients with PAD <75 years of age (vs 5% in control subjects; risk ratio [RR], 2.15; 95% confidence interval [CI], 1.60-4.34); 23% in diabetic patients with PAD <75 years of age (vs 7% in control subjects; RR, 3.53; 95% CI, 1.80-6.91); 38% in nondiabetic patients with PAD >= 75 years of age (vs 22% in control subjects; RR, 2.08; 95% CI, 1.26-3.44); and 52% in diabetic patients with PAD >= 75 years of age. Applying multivariate Cox proportional hazards regression analyses (with cardiovascular risk factors, coexisting atherosclerotic disease, clinical stage of PAD, and several biochemical markers as predictor variables), we found the following independent predictors of outcome: in the 216 nondiabetic patients with PAD <75 years of age, high-sensitivity C-reactive protein (hs-CRP) (RR, 3.04; 95% CI, 1.48-6.26); in the 115 diabetic patients with PAD <75 years of age, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) (RR, 2.63; 95% CI, 1.65-4.19); in the 102 nondiabetic patients with PAD >= 75 years of age, critical limb ischemia (RR, 3.70; 95% CI, 1.82-7.52) and NT-proBNP (RR, 1.93; 95% CI, 1.32-2.82); and in the 54 diabetic patients with PAD >= 75 years of age, hs-CRP (RR, 2.61; 95% CI, 1.45-4.67) and NT-proBNP (RR, 3.31; 95% CI, 1.96-5.60).Conclusions: Mortality rates at 5 years varied considerably among patients with PAD stratified according to age and diabetes. Predictors of death differed among the four patient subgroups in this study and included critical limb ischemia, hs-CRP, and NT-proBNP. Our results might help to develop future strategies for optimized treatment of hospitalized patients with symptomatic PAD.

In a 63-year-old cirrhotic patient, recanalisation of a partial portal vein thrombosis was achieved by a low dose of rivaroxaban (10mg daily). After anticoagulant therapy was stopped, partial vein thrombosis recurred. Restarting rivaroxaban at a dose of 10mg led to recanalisation. The patient did not suffer any complications; in particular no bleeding occurred during 8 months of treatment.

BACKGROUND : sST2 has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable coronary artery disease (CAD). METHODS : sST2 plasma concentrations were measured in 1345 patients with stable CAD referred for coronary angiography at a single tertiary care center. The primary endpoint was all-cause mortality. RESULTS : During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs 18.5 ng/mL; P (cid:2) 0.001). In multivariate Cox proportional hazards regression analysis, sST2 was an independent predictor of all-cause mortality (risk ratio 1.16 per 1SD increase in log-transformed values; 95% CI 1.05–1.29; P (cid:3) 0.004). In the same multivariate analysis, amino-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were also independent predictors, whereas galectin-3 was not. Patients with sST2 in the highest quartile ( (cid:4) 24.6 ng/mL) displayed a 2-fold increased risk of death in univariate analysis, which was attenuated but remained significant in a fully adjusted model (risk ratio 1.39; 95% CI 1.10–1.76;

Background: Soluble ST2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. There is no published data on sST2 in patients with stable coronary artery disease (CAD). Therefore, the aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable CAD.

B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism.

Objective: The evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure (HF).Design: Prospectively conducted study on diagnostic accuracy.Setting: Emergency department of a tertiary care hospital.Patients: 251 consecutive patients presenting to the emergency department with dyspnoea as the chief complaint.Main outcome measures: Index tests were plasma concentrations of 10 biomarkers (BNP, MR-proANP, MR-proADM, copeptin, CT-proET-1, ST2, adiponectin, chromogranin A, proguanylin and prouroguanylin). The reference standard was the diagnosis of acute destabilised HF, which was based on the Framingham score for HF plus echocardiographic evidence of systolic or diastolic dysfunction.Results: Median plasma concentrations of all 10 biomarkers were higher in patients with dyspnoea attributable to acute destabilised HF (n = 137) than in patients with dyspnoea attributable to other reasons (n = 114). Applying receiver operating characteristic curve (ROC) analyses, areas under the curve (AUCs) for BNP (0.92) and MR-proANP (0.88) were significantly higher than the AUCs of the other eight biomarkers (MR-proADM, 0.75; adiponectin, 0.73; CT-proET-1, 0.72; proguanylin, 0.68; ST2, 0.67; prouroguanylin, 0.62; copeptin, 0.62; and chromogranin A, 0.56). In multivariate logistic regression analysis only increased BNP and MR-proANP concentrations remained independent markers for the diagnosis of HF. Both markers alone or in combination added similar diagnostic information besides all clinical information available in the emergency department.Conclusions: The data showed that BNP and MR-proANP were the only independent diagnostic markers of HF. Both markers provided similar diagnostic information and were clinically useful as an aid in the diagnosis of acute destabilised HF in an emergency setting.