Effects of B-type natriuretic peptide on cardiovascular biomarkers in healthy volunteers.

Cardiovascular biomarkers provide independent prognostic information in the assessment of mortality and cardiovascular complications. However, little is known about possible interactions between these biomarkers. In the present study, we evaluated the influence of B-type natriuretic peptide (BNP) on midregional-proadrenomedullin (MR-proADM), C-terminal-proendothelin-1 (CT-proET-1), growth differentiation factor-15 (GDF-15), midregional-proatrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin in healthy volunteers. Ten healthy male subjects (mean age 24 yr) participating in a randomized, placebo-controlled, single-blinded crossover study received placebo or 3.0 pmol·kg(-1)·min(-1) human BNP 32 during a continuous infusion lasting for 4 h. Effects of BNP on other cardiovascular biomarkers were assessed. BNP did not change concentrations of MR-proADM, copeptin, CT-proET1, GDF-15, or procalcitonin. In contrast, MR-proANP was significantly decreased during BNP infusion. BNP as an established cardiovascular biomarker did not affect plasma concentrations of other cardiovascular biomarkers in a model of healthy volunteers.

Successful treatment of partial portal vein thrombosis (PVT) with low dose rivaroxaban.

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

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

AIMS/HYPOTHESIS: 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. METHODS: Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. RESULTS: Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. CONCLUSIONS/INTERPRETATION: Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01324739 FUNDING: The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

Evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure in patients with shortness of breath.

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.

[An unusual cause of severe abdominal pain]. / Massive diffuse Bauchschmerzen bei einem 33-jährigen bislang gesunden Mann.

A 33-year-old previously healthy man was admitted to the hospital with a 6-day history of diffuse abdominal pain and constipation. He was afebrile, looked unwell with a pale skin and displayed an elevated blood pressure. He had no peritoneal sign, and bowel sounds were normal. Blood tests were remarkable for a hematocrit of 26 % and mean cell volume of 83 fl, bilirubin levels were slightly elevated. Abdominal radiographs, abdominal ultrasound and computed tomography showed stool throughout the colon with a non-specific bowel gas pattern. Moreover, colonoscopy and gastroscopy provided no information on the underlying cause of the patient's severe pain. He was treated with fluids and spasmolytic drugs until the result of the urinary porphyrin level was received, which showed an elevated concentration of 1608 microg/d. Consequently, the plasma lead concentration was determined showing an elevated level of 92.3 microg/d. The examination of blood slides revealed erythrocytes with basophile stippling. On physical examination, a bluish discoloration could be seen along the gums. After starting the detoxication therapy with DMPS - 1800 mg p. o. for the first two days followed by 600 mg DMPS daily - the complaints disappeared. In spite of an extensive anamnestic exploration the source of the lead intoxication could not be found until now.

In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients.

Lipoprotein(a) (Lp(a)) consists of a low-density lipoprotein-like particle and a covalently linked highly glycosylated protein, called apolipoprotein(a) (apo(a)). Lp(a) derives from the liver but its catabolism is still poorly understood. Plasma concentrations of this highly atherogenic lipoprotein are elevated in hemodialysis (HD) patients, suggesting the kidney to be involved in Lp(a) catabolism. We therefore compared the in vivo turnover rates of both protein components from Lp(a) (i.e. apo(a) and apoB) determined by stable-isotope technology in seven HD patients with those of nine healthy controls. The fractional catabolic rate (FCR) of Lp(a)-apo(a) was significantly lower in HD patients compared with controls (0.164+/-0.114 vs 0.246+/-0.067 days(-1), P=0.042). The same was true for the FCR of Lp(a)-apoB (0.129+/-0.097 vs 0.299+/-0.142 days(-1), P=0.005). This resulted in a much longer residence time of 8.9 days for Lp(a)-apo(a) and 12.9 days for Lp(a)-apoB in HD patients compared with controls (4.4 and 3.9 days, respectively). The production rates of apo(a) and apoB from Lp(a) did not differ significantly between patients and controls and were even lower for patients when compared with controls with similar Lp(a) plasma concentrations. This in vivo turnover study is a further crucial step in understanding the mechanism of Lp(a) catabolism: the loss of renal function in HD patients causes elevated Lp(a) plasma levels because of decreased clearance but not increased production of Lp(a). The prolonged retention time of Lp(a) in HD patients might importantly contribute to the high risk of atherosclerosis in these patients.

Serum total 8-iso-prostaglandin F2alpha: a new and independent predictor of peripheral arterial disease.

OBJECTIVE: Circulating 8-iso-prostaglandin F 2alpha (8-iso-PGF 2alpha ) has been proposed as new indicator of oxidative stress, which is involved in the pathophysiologic changes of atherosclerosis. We proposed to test the hypothesis that 8-iso-PGF 2alpha is an independent predictor of symptomatic peripheral arterial disease (PAD). METHODS: A case-control study in 100 patients with symptomatic PAD and 100 control subjects matched for age, sex, and diabetes mellitus was conducted. Smokers and subjects using lipid-lowering drugs were excluded. Serum total 8-iso-PGF 2alpha was quantified with an enzyme immunoassay. RESULTS: Median 8-iso-PGF 2alpha was higher in patients with PAD than in control subjects (63 vs 42 pg/mL; P = .001). Logistic regression with hypertension, body mass index, and creatinine, low-density lipoprotein (LDL) cholesterol, triglyceride, high-sensitivity C-reactive protein (hs-CRP), 8-iso-PGF 2alpha , and total homocysteine concentrations as independent variables and case-control status as dependent variable revealed significant odds ratios (OR) for hypertension (OR, 3.74; 95% confidence interval [CI], 1.85-7.53), low-density lipoprotein cholesterol (OR, 1.16, for an increment of 10 mg/dL; 95% CI, 1.07-1.27), high-sensitivity C-reactive protein (OR, 1.02, for an increment of 1 mg/L; 95% CI, 1.00-1.03), and 8-iso-PGF 2alpha (OR, 1.11, for an increment of 10 pg/mL; 95% CI, 1.03-1.20). CONCLUSIONS: Serum total 8-iso-PGF 2alpha was an independent predictor of PAD in the population studied. This finding supports the hypothesis that 8-iso-PGF 2alpha is a risk marker for PAD. Our results indicate increased systemic oxidative stress in patients with PAD.