Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency.

OBJECTIVES: Our objective was to evaluate in a double-blind, randomized, placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels together with clinical and functional parameters, in a group of anemic patients with chronic heart failure (CHF) and chronic renal failure (CRF) receiving intravenous iron therapy, without recombinant human erythropoietin (rhEPO), versus placebo. BACKGROUND: Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem. This situation is linked with a variable inflammatory status. Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status, respectively. In this double-blind, randomized, placebo-controlled study, modifications in NT-proBNP and CRP level and clinical and functional parameters, in anemic patients with CHF and CRF receiving intravenous iron therapy, without rhEPO, versus placebo were evaluated. METHODS: Forty patients with hemoglobin (Hb) <12.5 g/dl, transferrin saturation <20%, ferritin <100 ng/ml, creatinine clearance (CrCl) <90 ml/min, and left ventricular ejection fraction (LVEF) < or =35% were randomized into 2 groups (n = 20 for each). For 5 weeks, group A received isotonic saline solution and group B received iron sucrose complex, 200 mg weekly. Minnesota Living with Heart Failure Questionnaire (MLHFQ) and 6-min walk (6MW) test were performed. NT-pro brain natriuretic peptide and CRP were evaluated throughout the study. No patients received erythroprotein any time. RESULTS: After 6 months follow-up, group B showed better hematology values and CrCl (p < 0.01) and lower NT-proBNP (117.5 +/- 87.4 pg/ml vs. 450.9 +/- 248.8 pg/ml, p < 0.01) and CRP (2.3 +/- 0.8 mg/l vs. 6.5 +/- 3.7 mg/l, p < 0.01). There was a correlation initially (p < 0.01) between Hb and NT-proBNP (group A: r = -0.94 and group B: r = -0.81) and after 6 months only in group A: r = -0.80. Similar correlations were observed with Hb and CRP. Left ventricular ejection fraction percentage (35.7 +/- 4.7 vs. 28.8 +/- 2.4), MLHFQ score, and 6MW test were all improved in group B (p < 0.01). Additionally, group B had fewer hospitalizations: 0 of 20 versus group A, 5 of 20 (p < 0.01; relative risk = 2.33). CONCLUSIONS: Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF. This situation was associated with an improvement in LVEF, NYHA functional class, exercise capacity, renal function, and better quality of life.     

内源性促红细胞生成素对慢性心力衰竭患者预后的影响

目的了解内源性促红细胞生成素(EPO)对慢性心力衰竭(CHF)患者预后的判定价值。方法选择住院的CHF患者115例,以患者是否存活分为死亡组55例,存活组60例。另选同期住院的年龄、性别相匹配的非CHF患者67例为对照组,以便建立logEPO和血红蛋白(Hb)的回归方程。对CHF患者进行全因死亡和因心力衰竭再次入院的随访观察,测定血EPO,并进行分析。结果与存活组比较,死亡组高龄患者多、心功能(NYHA)Ⅱ级比例低、Hb降低和B型钠尿肽(BNP)水平升高(P<0.01)。Kaplan-Meier生存曲线显示,贫血的CHF患者病死率增高(RR=2.50,95%CI:1.38～4.54,P=0.002)。ROC曲线评估EPO和BNP预测CHF患者死亡的最佳界值分别为44.4 U/L和752 ug/L(P=0.036,=0.000)。年龄、Hb、BNP和NYHA对CHF患者全因死亡有独立预测价值;而男性、BNP和Hb水平对因心力衰竭再次入院有独立预测价值。贫血的CHF患者EPO是独立于Hb的全因死亡的强预测指标(RR=2.86,95%CI:1.18～6.94,P=0.020)。结论贫血是CHF患者不良预后的独立预测因素。EPO是贫血CHF患者全因死亡的独立预测指标。     

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.     

The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study

OBJECTIVES: This is a randomized controlled study of anemic patients with severe congestive heart failure (CHF) to assess the effect of correction of the anemia on cardiac and renal function and hospitalization. BACKGROUND: Although mild anemia occurs frequently in patients with CHF, there is very little information about the effect of correcting it with erythropoietin (EPO) and intravenous iron. METHODS: Thirty-two patients with moderate to severe CHF (New York Heart Association [NYHA] class III to IV) who had a left ventricular ejection fraction (LVEF) of < or =40% despite maximally tolerated doses of CHF medications and whose hemoglobin (Hb) levels were persistently between 10.0 and 11.5 g% were randomized into two groups. Group A (16 patients) received subcutaneous EPO and IV iron to increase the level of Hb to at least 12.5 g%. In Group B (16 patients) the anemia was not treated. The doses of all the CHF medications were maintained at the maximally tolerated levels except for oral and intravenous (IV) furosemide, whose doses were increased or decreased according to the clinical need. RESULTS: Over a mean of 8.2+/-2.6 months, four patients in Group B and none in Group A died of CHF-related illnesses. The mean NYHA class improved by 42.1% in A and worsened by 11.4% in B. The LVEF increased by 5.5% in A and decreased by 5.4% in B. The serum creatinine did not change in A and increased by 28.6% in B. The need for oral and IV furosemide decreased by 51.3% and 91.3% respectively in A and increased by 28.5% and 28.0% respectively in B. The number of days spent in hospital compared with the same period of time before entering the study decreased by 79.0% in A and increased by 57.6% in B. CONCLUSIONS: When anemia in CHF is treated with EPO and IV iron, a marked improvement in cardiac and patient function is seen, associated with less hospitalization and renal impairment and less need for diuretics.     

Prevalence of anemia in patients admitted to hospital with a primary diagnosis of congestive heart failure

OBJECTIVES: To find the prevalence of anemia in patients hospitalized with the primary diagnosis of congestive heart failure (CHF). BACKGROUND: There is growing evidence that anemia is common in CHF and may contribute to the high morbidity and mortality associated with this condition. However, there is considerable disagreement about the prevalence of anemia in this condition. METHODS: In 338 consecutive patients who were admitted to the medical wards with a primary diagnosis of CHF we extracted from the charts the hemoglobin (Hb), serum creatinine, age, sex, New York Heart Association (NYHA) functional class, presence of smoking, diabetes, hypertension, hyperlipidemia and the primary cardiac etiology of the CHF. Anemia was considered to be present when the Hb on admission was <12 g/dl. RESULTS: All the patients were NYHA functional class III-IV. One hundred seventy seven (52.4%) of the 338 patients had a Hb on admission that was <12 g/dl. The mean Hb for the entire group was 12.0+/-1.8 g/dl. One hundred three (51.0%) of the 202 males were anemic compared to 74 (54.4%) of the 136 women. The mean serum creatinine was 1.7+/-1.1 mg/dl. The prevalence of renal insufficiency (serum creatinine >1.5 mg%) was 47.6%. There was a negative correlation between the level of serum creatinine and Hb (r=-0.294) P<0.00001. Of the 177 patients who were anemic, most of 114 (64.4%) had a serum creatinine >1.5 mg/dl. CONCLUSIONS: Anemia is a common finding in patients hospitalized with CHF and most anemic CHF patients have some degree of renal insufficiency. In view of the negative effect of anemia on cardiac function, it may be a common and important contributor to the mortality and morbidity of CHF in these patients.     

Comparison of the serum erythropoietin levels in chemotherapy-naive and cisplatin-treated cancer patients

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.     

Efficacy of nasal bi-level positive airway pressure in congestive heart failure patients with cheyne-stokes respiration and central sleep apnea.

BACKGROUND: Cheyne - Stokes respiration with central sleep apnea (CSR-CSA) contributes to the poor prognosis in patients with congestive heart failure (CHF). Bi-level positive airway pressure (bi-level PAP) may be an effective alternative for treating CSR-CSA and CHF. METHODS AND RESULTS: Fourteen patients with CSR-CSA were divided into 2 groups, a control group that included 7 patients who decided to receive only conventional medications and a group of 7 patients that received bi-level PAP. Left ventricular ejection fraction (LVEF), mitral regurgitation (MR) area, plasma brain natriuretic peptide (BNP) concentration and the New York Heart Association (NYHA) functional class were evaluated initially (baseline) and 3 months later. In the control group, there were no significant changes in cardiac function during the study period. In contrast, in the group that received bi-level PAP, there were significant improvements in LVEF (from 36.3+/-2.9% to 46.0+/-4.0%, p = 0.02), MR area (from 30.4+/-7.6% to 20.0+/-5.1%, p = 0.02), BNP (from 993.6+/-332.0 pg/ml to 474.0+/-257.6 pg/ml, p = 0.02) and NYHA functional class (from 3.1+/-0.1 to 2.1+/-0.1, p = 0.03). CONCLUSION: Treatment with bi-level PAP improved cardiac functions in CHF patients with CSR-CSA.     

Association of hyperadiponectinemia with severity of ventricular dysfunction in congestive heart failure.

BACKGROUND: Adiponectin, which is a collagen-like plasma protein produced by adipose tissue, has anti-atherogenic and anti-inflammatory effects. Plasma adiponectin levels in patients with congestive heart failure (CHF) were determined, as well as relationships between the plasma levels of adiponectin and other hormones. METHODS AND RESULTS: The study group comprised 90 patients with CHF and 20 control subjects, who were divided into 4 subgroups according to New York Heart Association (NYHA) functional class. Plasma levels of adiponectin, tumor necrosis factor (TNF)-alpha and brain natriuretic peptide (BNP) and cardiac hemodynamics were determined. Plasma adiponectin levels were significantly increased according to the severity of NYHA class in the patients with CHF; control: 6.2+/-1.0; NYHA I: 8.5+/-1.9, NYHA II: 12.0+/-2.2, NYHA III: 13.0+/-2.7, NYHA IV: 14.9+/-2.7 microg/ml (p=0.0008). Similarly, plasma BNP levels were significantly increased in accordance with the NYHA class. Plasma adiponectin levels correlated positively with BNP (r=0.40, p=0.0002) and TNF-alpha (r=0.49, p=0.0001), and correlated negatively with cardiac index (r=-0.27, p=0.05). In 24 of 46 patients in the NYHA III and IV subgroups, according to the prompt improvement in cardiac function, levels of both plasma adiponectin and BNP were significantly reduced (p<0.0001). CONCLUSION: Plasma adiponectin levels increased according to the severity of CHF and, moreover, they correlated with the plasma levels of BNP and TNF-alpha. These results indicate that augmented release of adiponectin is involved in the pathogenesis of CHF and further study is needed to elucidate its exact role.     

Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia.

AIMS: Anaemia is common in chronic heart failure (CHF) and associated with worse outcome. This randomized, double-blind, placebo-controlled study evaluated the effect of two darbepoetin alfa dosing regimens on haemoglobin (Hb) rate of rise and clinical effects in patients with CHF and anaemia. METHODS AND RESULTS: Patients with CHF (>or=3 months), left ventricular ejection fraction (LVEF) 相似文献   

Intravenous Iron in Heart Failure: Beyond Targeting Anemia

Iron deficiency is commonly seen in congestive heart failure (CHF) in both anemic and nonanemic patients. In six studies in which these iron-deficient patients with CHF were treated with intravenous (IV) iron, five found an improvement in the hemoglobin. In uncontrolled and controlled studies, the New York Heart Association (NYHA) class, quality of life, and exercise capacity were improved consistently with IV iron. In some studies, cardiac function also was improved. In one large, double-blind, placebo-controlled study of IV iron, the patient global assessment, quality of life, and NYHA class improved rapidly in both those who were anemic or not anemic. In contrast to these studies, another controlled study of anemia in CHF showed no effect of oral iron on hemoglobin or on any cardiac parameters over 1 year. These studies suggest that CHF in both anemic and nonanemic iron-deficient patients may benefit from a course of IV iron, but not oral iron.     

The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM: To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS: The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS: Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS: In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.     

促红细胞生成素及血红蛋白与老年慢性心力衰竭患者的相关性

目的探讨促红细胞生成素(EPO)和血红蛋白(Hb)与慢性心力衰竭(CHF)的相关性。方法选择老年CHF患者1 69例,根据本次住院确诊的心功能(NYHA)Ⅰ、Ⅱ、Ⅲ和Ⅳ级依次分为1组33例、2组34例、3组59例和4组4 3例。对4组患者Hb、EPO及是否死亡进行logistic回归分析。结果与1组比较,2、3和4组lg EPO水平明显上升,Hb水平明显下降(P<0.01);4组患者lg EPO和Hb水平两两比较,差异均有统计学意义(P<0.01)。Hb、EPO及肌酐(OR=0.978,35.820,1.013,P<0.01)均是影响老年CHF患者住院死亡的危险因素。结论 EPO随患者CHF程度的加重而升高,Hb值则降低。Hb、EPO及肌酐均为影响CHF患者住院死亡的危险因素。     

Influence of blood pressure profile on erythropoietin levels in diabetics

The purpose of this study was to investigate the relationships between 24-h BP profil and erythropoietin level in diabetics. PATIENTS AND METHODS: This study included 58 patients (26 women and 32 men, mean age: 58.7 +/- 14.6 yrs, diabetes duration: 16 +/- 11.2 yrs). Patients were divided by 24 hrs ABPM into 2 groups, one in which night-time pressures dipped by more than 10% (dippers, n = 16) and the other in which pressures dipped by less than 10% (non-dippers, n = 42) when compared to daytime pressures. Haemoglobin (Hb) and erythropoietin (EPO) levels where compared between diabetics and a control group (n = 110) and between dippers and non-dippers. RESULTS: Hb concentration of diabetics was significantly lower than those of control subjects (13.5 +/- 1.5 vs 14.5 +/- 1 g/dL; p < 0.0001) but EPO levels did not differ from significant manner between these two groups. EPO concentrations were lower in dippers than in control subjects (13.7 +/- 5.4 vs 17.9 +/- 5 mU/mL; p < 0.01), but there was not significant difference in Hb levels. Non-dippers had a Hb level lower than dippers (13.1 +/- 1.5 vs 14.6 +/- 1.1 g/dL, p < 0.0001), but EPO concentrations did not differ from significant manner. Hb was correlated with between daytime and night-time BP difference (SBP: r = 0.262; p < 0.05 and DBP: r = 0.396; p < 0.002). Hb was negatively correlated with albumin excretion rate (r = -0.335, p < 0.01) and with creatinine level (r = -0.419: p < 0.001). CONCLUSION: These data indicated that EPO production could be impaired in diabetics with abnormal diurnal BP variation. Nephropathy and cardiac autonomic dysfunction could explain these results.     

Heart rate variability in heart failure

BACKGROUND: Heart rate variability (HRV) depicts the functional status of the autonomic nervous system and its effects on sinus node. Recently, HRV analysis has been introduced in patients with heart failure (CHF) to identify those who are at risk of cardiac death. AIM: To analyse HRV in patients with CHF with depressed left ventricular ejection fraction (EF) and to relate HRV parameters to EF, NYHA functional class and other clinical parameters. METHODS: The study group consisted of 105 patients with CHF (88 males, 17 females, mean age 54+/-12 years); 77 patients had ischaemic cardiomyopathy, and 28 - dilated cardiomyopathy. All patients were in NYHA class II-IV and had EF <40%. The mean value of echocardiographically assessed EF was 26.9+/-8.3%. The control group consisted of 30 gender- and age-matched healthy subjects. HRV analysis was performed in the time-domain from 24-hour Holter ECG. RESULTS: All HRV variables were significantly lower in patients with CHF than in controls. Patients with NYHA class II had higher values of SDNN and SDANN than those in class III or IV. Patients with sustained or non-sustained ventricular tachycardia (VT) detected during Holter monitoring had lower SDNN and SDANN values than those without VT. Patients with diabetes had significantly lower SDNN and rMSSD values than the patients without diabetes. Similar results were found when patients with or without hypertension were compared. HRV parameters were similar in patients either with ischaemic or dilated cardiomyopathy. Also the values of EF were similar (27.4+/-8.4 vs 25.0+/-8.3%, respectively, NS). In the whole group of patients with CHF the values of SDNN and SDANN significantly correlated with EF (SDNN p<0.001, r=0.42; SDANN p<0.001, r=0.51). This correlation was stronger in the subset of patients with ischaemic cardiomyopathy (SDNN p=0.002. r=0.54; SDANN p=0.002; r=0.53) than in those with dilated cardiomyopathy (SDNN p=0.012, r=0.23; SDANN p=0.008, r=0.42). A significant negative correlation was found between all HRV parameters and NYHA class (SDNN p<0.001, r = -0.33; SDANN p<0.001, r = -0.38; rMSSD p<0.001, r = -0.13). CONCLUSIONS: HRV is depressed in patients with CHF compared with healthy subjects. Among patients with CHF, HRV is further decreased in patients with more advanced NYHA class, lower EF and in those with diabetes, hypertension or VT on Holter monitoring.     

Ongoing myocardial damage in chronic heart failure is related to activated tumor necrosis factor and Fas/Fas ligand system.

BACKGROUND: Elevated concentrations of cardiac troponin T and heart-type fatty acid-binding protein (H-FABP) identify patients with chronic heart failure (CHF) and ongoing myocardial damage (OMD) who are at increased risk for future cardiac events. Cardiomyocyte necrosis and/or apoptosis via activated tumor necrosis factor (TNF) and the Fas/Fas ligand (FasL) system may be related to the development of OMD. METHODS AND RESULTS: The serum concentrations of H-FABP, a sensitive marker of membrane damage of cardiomyocytes, soluble Fas (sFas) and TNF-alpha were measured in 38 patients with CHF. The concentrations of H-FABP, TNF-alpha and s-Fas in patients with New York Heart Association (NYHA) III + IV were all significantly higher than in those patients in NYHA II (H-FABP; III + IV 9.3+/-5.9 vs II 5.1+/-1.8 ng/ml, p=0.003, TNF-alpha; III + IV 10.5+/-3.8 vs II 8.0+/-2.7 pg/ml, p=0.02, sFas; III + IV 3.36+/-1.37 vs II 2.58 +/-0.84 ng/ml, p=0.03). Increased concentrations of H-FABP significantly correlated with the concentrations of TNF- alpha (r=0.57, p=0.0001) and sFas (r=0.69, p<0.0001), independent of renal function. CONCLUSION: OMD detected by H-FABP, a marker of membrane damage, is related to activated TNF and the Fas/FasL system, which suggests a pathophysiological role of cardiomyocyte necrosis and/or apoptosis in patients with worsening heart failure.     

Serum erythropoietin levels in the elderly.

We evaluated the relationship between erythropoietin (EPO) and hemoglobin (Hb) concentrations in 156 normal subjects ranging from 60 to 98 years old. EPO was determined by a radioimmunoassay. The serum EPO concentration in subjects with Hb concentrations greater than 12.0 g/dl (26.9 +/- 15.2 mU/ml), was significantly higher than that in younger controls (15.8 +/- 5.0 mU/ml, p less than 0.001). No sex difference in serum EPO level was detected. In addition, there was an inverse semilogarithmic relationship between EPO and Hb concentrations in subjects with Hb concentrations less than 12.0 g/dl (r = -0.559, p less than 0.001). EPO concentrations in the elderly were lower than those in young subjects with iron deficiency anemia with the same Hb level. Thus, in the elderly, a high EPO concentration may be preventing a decrease in the Hb concentration. However, a decreased EPO response to low Hb concentrations may be a contributing factor in anemia in the elderly.     

Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure

BACKGROUND: Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels. AIM: To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF. METHODS AND RESULTS: Thirty stable NYHA classes II-III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25-50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class (p=0.013), increased left ventricular ejection fraction (LVEF) (24+/-1.4% to 31+/-2.3%, p=0.003) and 6-min walk distance (499+/-18 to 534+/-18 m, p=0.03), without changes in the peak VO2. At baseline, norepinephrine (NE) plasma levels increased with exercise (510+/-51 to 2513+/-230 pg/mL, p<0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049+/-0.001 to 0.042+/-0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4+/-0.2 to 1.1+/-0.2 microM, p<0.001), without changes in antioxidant enzyme activities. CONCLUSIONS: Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.     

Influence of blood pressure level on urinary albumin excretion rate and erythropoietin production in diabetic patients

The purpose of this study was to investigate blood pressure variations during diabetic incipient nephropathy and to evaluate theirs consequences for erythropoietin (EPO) production. PATIENTS AND METHODS: This study included 94 diabetic patients (mean age: 59.9 +/- 15.3 years, diabetes duration: 13.8 +/- 15.3 years). Patients were divided in two groups according to urinary albumin excretion rate (UAE): group 1: UAE <30 mg/24 hrs, N=64 and group 2: 30相似文献   

Can serum NT-proBNP detect changes of functional capacity in patients with chronic heart failure?

Recently, in a cross-sectional study, a correlation of moderate degree was documented between serum BNP (brain natriuretic peptide) and exercise capacity in patients with chronic heart failure (CHF). However, it remains unknown if BNP, which increases in response to high myocardial wall stress, is sufficiently sensitive for changes in exercise capacity during clinical follow-up. To elucidate this, 42 CHF patients were recruited and randomized into a training (T; 58 +/- 10 years; n = 14 NYHA II; n = 5 NYHA III) and a control group (CO; 54 +/- 9, n = 17 NYHA II; n = 6 NYHA III). T carried out 12 weeks of endurance training on a cycle ergometer (4 sessions per week, 45 min duration). Venous blood sampling and cycle ergometry with simultaneous gas exchange measurements were carried out prior to and after the experimental phase. Due to its superior stability during laboratory procedures, NTproBNP was determined instead of BNP. Both proteins are secreted in equimolar amounts and share an identical diagnostic meaning. In both groups, NT-proBNP decreased slightly (T: from 1092 +/- 980 to 805 +/- 724 pg x ml(-1); CO: from 1075 +/- 1068 to 857 +/- 1138 pg x ml(-1); T vs CO: p = 0.65). Anaerobic threshold (AT) as a measure of exercise capacity went up in T (from 0.96 +/- 0.17 to 1.10 +/- 0.22 l x min(-1)) but remained almost constant in CO (pre: 1.02 +/- 0.27; post: 1.00 +/- 0.27 l x min(-1); T vs CO: p < 0.001). The correlation between changes in NT-proBNP and changes in AT remained insignificant (r = 0.02, p = 0.89)-even if only T was considered (r = 0.09, p = 0.72). Improved exercise capacity in CHF patients due to 3 months of endurance training is not reflected in the course of NT-proBNP. These findings are inconsistent with a sufficient sensitivity of this parameter to detect changes in exercise capacity during clinical follow-up. Changes in NT-proBNP beyond its spontaneous variability are more likely to be detected following therapeutical interventions which aim more clearly at the myocardium. In determining alterations of functional capacity ergometric testing cannot be replaced by serial determinations of NT-proBNP.     

Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity

BACKGROUND: Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. METHODS: Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). RESULTS: The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4+/-4.2 versus 17.8+/-4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1+/-6.8 versus 34+/-5.3, p<0.0001). In the univariate model, age (r=-0.36, p<0.0001), female sex (r=-0.21, p=0.001), ischemic CHF etiology (r=-0.26, p<0.0001) and NYHA class (r=-0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology (beta=-0.23, p=0.001) was a predictor of peak VO2 (R(2)=0.49) independently of age (beta=-0.23, p=0.001), female sex (beta=-0.25, p=0.0006) and NYHA class (beta=-0.31, p<0.0001). Similarly, ischemic etiology (beta=0.29, p=0.001) predicted the VE/VCO2 slope (R(2)=0.38) independently of E/A ratio (beta=0.27, p=0.01) and resting heart rate (beta=0.22, p=0.01). CONCLUSIONS: Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.