Influence of hydroxyethyl starch (6% HES 130/0.4) administration on hematology and clinical chemistry parameters

Background: The chemical inertness of hydroxyethyl starch (HES) might cause interferences of the colloid with a variety of laboratory tests. We aimed to evaluate potential influences of HES 130/0.4, the newest HES type, on several common hematology and clinical chemistry parameters. Methods and results: A convenient sample of 25 patients scheduled for rheological therapy with 500 mL 6% HES 130/0.4 was evaluated. Blood samples were drawn before and after colloid application. Comparing pre- and post-infusion values of a battery of laboratory tests (i.e., hematology and hemostasis parameters, electrolytes, enzymes, kidney and metabolic parameters, lipids, etc.) in time course, a median difference greater than the reference change value for a specific parameter was considered clinically relevant. Among all parameters tested, only serum amylase activity displayed a clinically relevant difference between pre- and post-infusion values (median increase of 85% due to HES administration). By applying in vitro experiments, we demonstrated that serum amylase values obtained in the samples diluted in a 1:1 ratio with HES 130/0.4 and in samples diluted in a 1:1 ratio with 0.9% NaCl displayed a negligible median difference of 3%. Conclusions: The in vivo effect of HES 130/0.4 administration on serum amylase activity observed in our study was pharmacological (real) in nature. With the exception of the influence of HES 130/0.4 on amylase activity, the effects of HES 130/0.4 on other parameters tested in this study can be interpreted as having no clinical relevance

Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation factor-15 with heart failure and other non-cardiac diseases

AbstractBackgroundThe biomarkers soluble ST2 (sST2), galectin-3, and growth-differentiation factor-15 (GDF-15) provide prognostic information in patients with heart failure (HF). The aim of this study was to evaluate to which extent plasma concentrations of these biomarkers are increased in HF compared with diverse non-cardiac conditions such as infectious disease or chronic kidney disease.MethodsWe recruited 15 patients in each of the following clinical categories: HF without co-morbidity, pneumonia without co-morbidity, chronic obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity of pneumonia, renal disease without co-morbidity, and sepsis. We used 22 healthy individuals as control group. In each of the 112 study participants, we measured plasma concentrations of sST2 (Presage assay), galectin-3 (Abbott assay) and GDF-15 (Roche assay).ResultsCompared to controls, the median sST2 concentration was ~2.5-fold increased in HF, ~3.5-fold in pneumonia, ~5.0-fold in COPD, ~5.8-fold in HF+pneumonia, and ~70-fold in sepsis (p<0.001 for all). sST2 was not significantly increased in renal disease. Compared to controls, the median galectin-3 concentration was ~1.5-fold increased in HF, ~1.4-fold in pneumonia, ~2.4-fold in HF+pneumonia, ~2.5-fold in renal disease, and ~2.7-fold in sepsis (p<0.001 for all). Galectin-3 was not significantly increased in COPD. Compared to controls, the median GDF-15 concentration was ~4.4-fold increased in HF, ~5.4-fold in pneumonia, ~2.1-fold in COPD, ~8.3-fold in HF+pneumonia, ~5.1-fold in renal disease, and ~27-fold in sepsis (p<0.001). In the 112 study participants, correlation analyses revealed a relatively strong association between galectin-3 and GDF-15 (correlation coefficient, 0.739; p<0.001).ConclusionBecause increased plasma concentrations of sST2, galectin-3, and GDF-15 are not specific for a distinct disease group, the three biomarkers are not useful for diagnostic purposes. The results of our study are novel with respect to sST2, galectin-3 and GDF-15 as markers of inflammatory diseases and should encourage further studies

Are soluble ST2 levels influenced by vitamin D and/or the seasons?

Objective: Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability. Design: sST2 levels were measured in two cohorts involving hypertensive patients at cardiovascular risk, the Styrian Vitamin D Hypertension Trial (study A; RCT design, 8 weeks 2800 IU cholecalciferol daily) and the Ludwigshafen Risk and Cardiovascular Health Study (LURIC; study B; cross-sectional design). Methods: The effects of a vitamin D intervention on sST2 levels were determined in study A using ANCOVA, while seasonality of sST2 levels was determined in study B using ANOVA. Results: The concentrations of sST2 remained unchanged by a vitamin D intervention in study A, with a mean treatment effect (95% confidence interval) of 0.1 (−0.6 to 0.8) ng/mL; P = 0.761), despite a rise in 25(OH)D (11.3 (9.2–13.5) ng/mL; P < 0.001) compared to placebo. In study B, seasonal variations were present in 25(OH)D levels in men and women with or without heart failure (P < 0.001 for all subgroups), while sST2 levels remained unaffected by the seasons in all subgroups. Conclusions: Our study provides the first evidence that systemic sST2 levels are not interrelated with vitamin D levels or influenced by the seasons in subjects at cardiovascular risk

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts

The heart matters in diabetes: 10-Year outcomes of peripheral artery disease

Objectives: Mortality rates at 10 years are higher in diabetic patients with chronic lower extremity peripheral arterial disease than in non-diabetic peripheral arterial disease patients. We tested the hypothesis that the predictors of mortality differ between diabetic and non-diabetic peripheral arterial disease patients. Methods: We studied 331 consecutive patients who were <75 years of age, symptomatic for peripheral arterial disease, and admitted to a tertiary care hospital. Our cohort included 216 patients without diabetes mellitus and 115 with diabetes mellitus. The outcome measure was all-cause mortality at 10 years post-admission. Results: Mortality rates at 10 years were 29% among non-diabetic peripheral arterial disease patients and 58% among diabetic peripheral arterial disease patients. We identified the following independent predictors of death in the 216 peripheral arterial disease patients without diabetes: age ≥65 years (risk ratio: 2.15; 95% confidence interval: 1.28–3.59), ankle brachial index <0.60 mmHg/mmHg (risk ratio: 1.88; 95% confidence interval: 1.14–3.08), history of peripheral arterial disease-specific intervention (risk ratio: 1.81; 95% confidence interval: 1.10–2.97), and high-sensitivity C-reactive protein ≥5.0 mg/L (risk ratio: 2.11; 95% confidence interval: 1.28–3.47). For the 115 peripheral arterial disease patients with diabetes, independent predictors of mortality were as follows: age ≥65 years (risk ratio: 1.72; 95% confidence interval: 1.05–2.83) and amino-terminal pro-B-type natriuretic peptide ≥125 ng/L (risk ratio: 2.10; 95% confidence interval: 1.22–3.60). Conclusion: In this study, the predictors of death at 10 years differed between peripheral arterial disease patients with and without diabetes. Among the biomarkers tested, high-sensitivity C-reactive protein was independently associated with outcomes in non-diabetic patients, whereas amino-terminal pro-B-type natriuretic peptide was an independent predictor of death in patients with diabetes. Our findings suggest that in future studies, risk assessment and treatment strategies should be differentially applied to the two peripheral arterial disease subgroups