Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study

<p><b>Context:</b> The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF).</p> <p><b>Objectives:</b> We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP).</p> <p><b>Methods:</b> Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years).</p> <p><b>Results:</b> Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF.</p> <p><b>Discussion:</b> The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF.</p> <p><b>Conclusions:</b> Big-ET-1improves risk stratification in patients referred for coronary angiography.</p

Effect of High-Flux Dialysis on Circulating FGF-23 Levels in End-Stage Renal Disease Patients: Results from a Randomized Trial

<div><p>Background</p><p>In patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. Interventional strategies aiming to reduce levels of FGF-23 in HD patients are of particular interest. The purpose of the current study was to compare the impact of high-flux versus low-flux HD on circulating FGF-23 levels.</p><p>Methods</p><p>We conducted a post-hoc analysis of the MINOXIS study, including 127 dialysis patients randomized to low-flux (n = 62) and high-flux (n = 65) HD for 52 weeks. Patients with valid measures for FGF-23 investigated baseline and after 52 weeks were included.</p><p>Results</p><p>Compared to baseline, a significant increase in FGF-23 levels after one year of low-flux HD was observed (Delta plasma FGF-23: +4026 RU/ml; p < 0.001). In contrast, FGF-23 levels remained stable in the high flux group (Delta plasma FGF-23: +373 RU/ml, p = 0.70). The adjusted difference of the absolute change in FGF-23 levels between the two treatment groups was statistically significant (p < 0.01).</p><p>Conclusions</p><p>Over a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23. However, the implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in specifically designed clinical trials.</p><p>Trial Registration</p><p>German Clinical Trials Register (DRKS) <a href="https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML#x0026;TRIAL_ID=DRKS00007612" target="_blank">DRKS00007612</a>.</p></div

Baseline characteristics of the study population.

<p>Values presented with numbers in parentheses are mean (SD). CHD, coronary heart disease; MI, myocardial infarction; CHF, congestive heart failure; hs-CRP, high-sensitivity C-reactive protein; UF, ultrafiltration; HMG-CoA, hydroxymethyl glutaryl coenzyme A; ASS, acetylsalicylic acid.</p><p>^a Median (interquartile range).</p><p>Baseline characteristics of the study population.</p

Flow chart of the MINOXIS study.

<p>Flow chart of the MINOXIS study.</p

Outcome.

<p>Outcome.</p

Grouped boxplots visualizing the distributions of FGF-23 before and after the intervention stratified by randomization group.

<p>Black box: FGF-23 before the intervention, Grey box: FGF-23 after the intervention. 1: low-flux group, 2: high-flux group.</p

FGF-23; predicted marginal means of the absolute difference (12 months—baseline).

<p>FGF-23; predicted marginal means of the absolute difference (12 months—baseline).</p

Relative catheter positions and plasma influx.

<p>a) If the venous insertion point (y) is higher relative to the tip (x), there is no plasma or in-vivo whole blood influx b) If the venous insertion point is lower (y) relative to the tip (x) plasma or in-vivo whole blood enters the lumens of the catheter (as indicated by green colour). The same relative catheter position can be assumed for patients in upright position with femoral catheters.</p

Cholesterol efflux capacity.

<p>Apolipoprotein B (apoB)-depleted sera of healthy subjects (control, n = 27) and patients with age-related macular degeneration (AMD, n = 29) were examined for (A) their ability to promote [³H]-cholesterol efflux from macrophages. [³H]-cholesterol-labeled RAW264.7 macrophages were incubated with 2.8% apoB-depleted sera for 4 hours. Cholesterol efflux is expressed as radioactivity in the supernatant relative to total radioactivity (in supernatant and cells). Values shown represent means of two independent experiments.</p

Results of in-vitro protein precipitation tests (dilution studies).

<p>^a Test solutions consisted of 1 ml plasma (or serum) and 4 ml ethanol lock solution (V0– V9, concentrations ranged from 70 to 7%).</p><p>^b mimicking the conditions inside the catheter. Tests were conducted at room and body temperature.</p><p>^c Precipitation was assessed with a visual score, ranging from +++ (much) to – (none).</p><p>^d Blood sample characteristics: hematocrit 0,42; albumin 4.5 g/dl; total protein 6.5 g/dl.</p