Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure

OBJECTIVES: This study aimed to investigate the prognostic importance of plasma erythropoietin (EPO) levels in chronic heart failure (CHF) patients. BACKGROUND: Anemia is common and is associated with an impaired survival in patients with CHF. Erythropoietin is a hematopoietic growth factor, upregulated in anemic conditions. Little is known about the pathophysiology of anemia in CHF and the prognostic importance of plasma EPO levels in CHF patients. METHODS: In 74 patients with CHF (age, 61 +/- 2 years; left ventricular ejection fraction, 0.31 +/- 0.01; peak oxygen consumption, 19.1 +/- 0.6 [mean +/- SEM]) and in 15 control patients, hemoglobin levels and plasma concentrations of EPO and brain natriuretic peptide were measured. RESULTS: During a mean follow-up of 3.0 years (range, 2.3 to 5.3 years), 22 patients (30%) died. Anemia was present in 24% of the patients. Multivariate analysis showed that plasma EPO (p = 0.026) and hemoglobin levels (p = 0.005) were independent predictors of survival in this CHF population. We observed only a mild inverse correlation between the logarithm of EPO and hemoglobin levels (r2 = 0.08, p = 0.02) in CHF patients, whereas the control group showed a clear significant inverse correlation (r2 = 0.44, p = 0.007). CONCLUSIONS: Elevated plasma EPO levels are associated with an impaired prognosis independent of hemoglobin levels and other established markers of CHF severity. Furthermore, in the CHF patients, EPO levels poorly correlate with the hemoglobin levels, in contrast with the control group.     

Predictors of Functional Recovery in Patients Admitted to Geriatric Postacute Rehabilitation

Objective

To examine characteristics associated with functional recovery in older patients undergoing postacute rehabilitation.

Design

Observational study.

Setting

Postacute rehabilitation facility.

Participants

Patients (N=2754) aged ≥65 years admitted over a 4-year period.

Interventions

Not applicable.

Main Outcome Measure

Functional status was assessed at admission and again at discharge. Functional recovery was defined as achieving at least 30% improvement on the Barthel Index score from admission compared with the maximum possible room for improvement.

Results

Patients who achieved functional recovery (70.3%) were younger and were more likely to be women, live alone, and be without any formal home care before admission, and they had fewer chronic diseases (all P<.01). They also had better cognitive status and a higher Barthel Index score both at admission (mean ± SD, 63.3±18.0 vs 59.6±24.7) and at discharge (mean ± SD, 86.8±10.4 vs 62.2±22.9) (all P<.001). In multivariate analysis, patients <75 years of age (adjusted odds ratio [OR]=1.51; 95% confidence interval [CI], 1.16–1.98; P=.003), women (adjusted OR=1.24; 95% CI, 1.01–1.52; P=.045), patients living alone (adjusted OR=1.61; 95% CI, 1.31–1.98; P<.001), and patients without in-home help prior to admission (adjusted OR=1.39; 95% CI, 1.15–1.69; P=.001) remained at increased odds of functional recovery. In addition, compared with those with moderate-to-severe cognitive impairment (Mini-Mental State Examination score <18), patients with mild-to-moderate impairment (Mini-Mental State Examination score 19–23) and those cognitively intact also had increased odds of functional recovery (adjusted OR=1.56; 95% CI, 1.13–2.15; P=.007; adjusted OR=2.21; 95% CI, 1.67–2.93; P<.001, respectively).

Conclusions

Apart from sociodemographic characteristics, cognition is the strongest factor that identifies older patients more likely to improve during postacute rehabilitation. Further study needs to determine how to best adapt rehabilitation processes to better meet the specific needs of this population and optimize their outcome.     

The revised role of ACE-inhibition after myocardial infarction in the thrombolytic/primary PCI era.

Many studies have investigated the process of left ventricular (LV) dilatation and the effects of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction (MI). It has been generally accepted that progression of LV dilatation is a major predictor of heart failure and death after MI. Also, attenuation of LV dilatation is thought to be one of the main mechanisms by which ACE inhibitors (ACE-Is) produce their beneficial effects. However, evidence for this hypothesis came from studies that were performed before thrombolytic therapy and primary percutaneous coronary intervention (PCI) were routinely used after acute MI. Nowadays, reperfusion is obtained much more frequently and LV dilatation after MI has become less prevalent. Nevertheless, ACE-Is proved effective in reducing cardiac morbidity and mortality. Therefore, mechanisms other than attenuation of LV dilatation, such as anti-atherosclerotic effects or plaque stabilisation, may explain the long-term beneficial effects of ACE-Is after MI. In the present overview, we evaluate the role of LV dilatation and the effects of ACE-Is after MI in the thrombolytic/primary PCI era and provide recommendations on ACE-I use in clinical practice.     

Novel immunomodulator FTY720 is phosphorylated in rats and humans to form a single stereoisomer. Identification, chemical proof, and biological characterization of the biologically active species and its enantiomer

In vivo phosphorylation of FTY720 (1) in rats and humans resulted exclusively in the biologically active (S)-configured enantiomer, which was proven by an ex vivo o-phthaldialdehyde derivatization protocol especially elaborated for phosphates of 1. Starting from the prochiral amino alcohol 1, racemic and enantiomerically pure phosphates of 1 were synthesized. Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction.     

Hydrochlorothiazide increases plasma or tissue angiotensin-converting enzyme-inhibitor drug levels in rats with myocardial infarction: differential effects on lisinopril and zofenopril

Sodium depletion with diuretics augments the efficacy of angiotensin-converting enzyme-inhibitor therapy for hypertension and renal dysfunction, and possibly for left ventricular dysfunction after myocardial infarction. Underlying mechanisms may involve altered angiotensin-converting enzyme-inhibitor pharmacokinetics. We hypothesized that the diuretic hydrochlorothiazide causes increased steady-state levels of the angiotensin-converting enzyme-inhibitors lisinopril and zofenopril in rats with myocardial infarction. Rats were subjected to coronary ligation to induce myocardial infarction. After 1 week, rats were randomized to 50 mg/kg/day hydrochlorothiazide or control treatment for 3 weeks. The last week, rats received lisinopril or zofenopril in equipotentent dosages (3.3 and 10 mg/kg/day, respectively). Rats were sacrificed at Tmax after the last dose of angiotensin-converting enzyme-inhibitor, and tissues were collected for analysis of drug concentrations. Lisinopril concentrations in plasma were significantly increased by hydrochlorothiazide, at unchanged tissue concentrations. This increase could be fully explained by decreased renal function, as evidenced by increased plasma creatinine levels (lisinopril + hydrochlorothiazide 82+/-5 microM versus lisinopril 61+/-5 microM, P < 0.001). In contrast, zofenoprilat levels in kidney and non-infarcted left ventricle were markedly increased by hydrochlorothiazide, whereas plasma concentrations were unchanged. Although hydrochlorothiazide tended to increase plasma creatinine in zofenopril-treated rats as well, this increase was less pronounced (zofenopril + hydrochlorothiazide 61+/-3 microM versus zofenopril 54+/-2 microM, P = 0.15). Hydrochlorothiazide increases steady-state angiotensin-converting enzyme-inhibitor drug levels, most likely by affecting their renal clearance. Notably, the lipophilic angiotensin-converting enzyme-inhibitor zofenopril accumulated in tissue, whereas the hydrophilic lisinopril increased in plasma. Whether combining different angiotensin-converting enzyme-inhibitors with hydrochlorothiazide translates into distinct clinical profiles requires further study.     

Influence of catheter intervention on platelet function and activation in a pig model for endovascular embolization of arteriovenous malformations

Catheter interventions are associated with the risk of thromboembolism; however, the extent of platelet activation is not known. Samples from an arteriovenous malformation model (n?=?21 pigs) were examined. The pigs received a continuous infusion of 66?IU?kg^?1?h^?1 (n?=?11) or 100?IU?kg^?1?h^?1 (n?=?10) heparin applied 20?min after an initial bolus of 100?IU/kg. Platelet aggregation according to Born and ADVIA 120? platelet activation indices were used to study platelet function and activation. Samples were taken previous to vascular puncture, following vascular puncture, 20?min after application of heparin bolus, following placement of microcatheters and after endovascular embolization. Reactivity of platelets was increased after puncture of the vessels (ADP: P?<?0. 0001, collagen: P?=?0.0053). Further on activity of platelets was constrained by heparinization (ADP: P?<?0.0001, collagen P?<?0.0001). It can be concluded that the puncture of vessels yields the highest risk of thromboembolic complications.     

Monitoring of heparin therapy and establishment of an optimal therapy scheme for thrombosis prophylaxis in a pig model for human catheter interventions

This study aims to investigate variables suitable for monitoring of unfractionated heparin (UFH) therapy and establishment of an optimal therapy scheme in pigs. This is a prospective study of 32 pigs undergoing catheterization for endovascular embolization of experimentally induced arteriovenous malformation. Pigs were assigned to four groups receiving different UFH treatment during catheter intervention. In groups?1 and 2, UFH was applied as a bolus of either 100?IU/kg (n?=?6) and 200?IU/kg (n?=?6). Groups?3 and 4 received a continuous infusion of 66?IU/kg/h?UFH (n?=?10) and 100?IU/kg/h (n?=?10), respectively, which was applied 20?min after an initial bolus of 100?IU/kg. Blood samples were taken 0, 10, 20, 40, 60, 100, and 140?min after starting catheterization (groups?1?+?2) and after 0, 10, 20, 30, 40, 50, 60, 80, 100, 120, and 140?min, respectively (groups 3?+?4). High/low range activated coagulation time (LR-ACT), activated partial thromboplastin time (aPTT), prothrombin time, fibrinogen, and anti-FactorXa activity (FXa) activity were assessed. Based on anti-FXa activity, bolus injection of 100 and 200?IU/kg UFH had a mean half-life of 28.43?±?8.85 and 57.05?±?12.42?min, however, an aPTT exceeding 999?s was present in four of seven pigs in group?2. In group?3, aPTT increased from baseline 15?±?2?s to a steady state ranging from 30 to 33?s. In group?4, there was an increase of aPTT to 58?±?23?s 140?min after initiation of treatment. Suitable variables for monitoring UFH therapy included anti-FXa activity, aPTT, and LR-ACT. An initial bolus of 100?IU/kg?followed by a continuous UFH infusion of 66?IU?UFH/kg/h can be recommended as antithrombotic therapy during catheterization.