Secondary hyperparathyroidism prevalence and prognostic role in elderly males with heart failure.

AIM: Evaluation of secondary hyperparathyroidism (SHPT) and its prognostic impact on all-cause mortality in elderly males with heart failure (HF). METHODS: Seventy three males (67 ± 7 years old) with systolic HF were included. Baseline PTH was measured. Patients were grouped according to PTH cut-off levels of 65 pg/ml (>65 pg/ml = SHPT vs. normal PTH). All-cause mortality was evaluated at 6-year follow-up. RESULTS: SHPT was diagnosed in 43 (59 %) patients. They were more severe compared to the patients with normal PTH regarding NYHA functional class (2.4 ± 0.5 vs. 2.1 ± 0.2, p = 0.001), quality of life score (34 ± 14 vs. 24 ± 12, p = 0.005), 6-min walking distance (378 ± 79 vs. 446 ± 73 m, p < 0.0001), left ventricular ejection fraction (27 ± 8 vs. 31 ± 7 %, p = 0.019), and NT-proBNP [2452 (3399) vs. 918 (1372) pg/ml, p < 0.0001]. No differences in age, vitamin D status, and renal function were noted between studied groups. A total of 41 (56 %) patients died within 6 years of follow-up. Kaplan-Meier survival analysis showed impaired long-term survival in patients with SHPT versus patients with normal PTH (p = 0.009). The rate of death was highest (75 %) in the group of patients with SHPT and NT-proBNP levels above median value (p = 0.003). Cox regression analysis demonstrated that NT-proBNP was the single independent predictor of all-cause mortality at 6-year follow-up [HR 3.698 (1.927-7.095), p < 0.0001]. CONCLUSION: SHPT was highly prevalent in elderly males with HF and was associated with impaired survival. HF patients with SHPT had more severe disease compared to the patients with normal serum PTH. Determination of serum PTH levels provided additional value to NT-proBNP for risk stratification in these patients.

Plasma adiponectin in heart failure with and without cachexia: catabolic signal linking catabolism, symptomatic status, and prognosis.

BACKGROUND AND AIMS: Adiponectin (ADPN) as an adipose tissue hormone contributes to regulation of energy metabolism and body composition and is associated with cardiovascular risk profile parameters. Cardiac cachexia may develop as a result of severe catabolic derangement in chronic heart failure (CHF). We aimed to determinate an abnormal ADPN regulation as a link between catabolic signalling, symptomatic deterioration and poor prognosis. METHODS AND RESULTS: We measured plasma ADPN in 111 CHF patients (age 65 ± 11, 90% male, left ventricular ejection fraction (LVEF) 36 ± 11%, peak oxygen consumption (peakVO2) 18.1 ± 5.7 l/kg*min, body mass index (BMI) 27 ± 4 kg/m(2), all mean ± standard deviation) and 36 healthy controls of similar age and BMI. Body composition was assessed by dual energy X-ray absorptiometry, insulin sensitivity was evaluated by homoeostasis model assessment, exercise capacity by spiroergometry. Plasma ADPN did not differ between CHF vs. controls (13.5 ± 11.0 vs. 10.5 ± 5.3 mg/l, p > 0.4), but increased stepwise with NYHA functional class (I/II/III: 5.7 ± 1.4/10.7 ± 8.3/19.2 ± 14.0 mg/l, ANOVA p < 0.01). Furthermore, ADPN correlated with VO2 at anaerobic threshold (r = -0.34, p < 0.05). ADPN was highest in cachectic patients (cCHF, 16%) vs. non-cachectic (ncCHF) (18.7 ± 15.0 vs. 12.5 ± 9.9 mg/l; p < 0.05). ADPN indicated mortality risk independently of established prognosticators (HR: 1.04 95% CI: 1.02-1.07; p < 0.0001). ADPN above the mean (13.5 mg/l) was associated with a 3.4 times higher mortality risk in CHF vs. patients with ADPN levels below the mean. CONCLUSION: Circulating ADPN is abnormally regulated in CHF. ADPN may be involved in impaired metabolic signalling linking disease progression, tissue wasting, and poor outcome in CHF.

Characteristics associated with occurrence of stroke in patients with infective endocarditis - a retrospective cohort study.

BACKGROUND: Stroke is a severe complication of infective endocarditis (IE), associated with high rates of mortality. Data on how IE patients with and without stroke differ may help to improve understanding contributing mechanisms. METHODS: All patients treated for IE between 2019 and 2021 with and without associated stroke were identified from the medical records of three academic tertiary care hospitals in Germany, all part of Charité - Universitätsmedizin Berlin, Germany. Multivariable logistic regression analyses were performed to identify variables associated with the occurrence of stroke. RESULTS: The study population consisted of 353 patients diagnosed with IE. Concomitant stroke occurred in 96/353 (27.2%) patients. Acute stroke was independently associated with co-occurring extracerebral arterial embolism [adjusted Odds ratio (aOR = 2.52; 95% confidence interval (CI) 1.35-4.71)], acute liver failure (aOR = 2.62; 95% CI 1.06-6.50), dental focus of infection (aOR = 3.14; 95% CI 1.21-8.12) and left-sided IE (aOR = 28.26; 95% CI 3.59-222.19). Stroke was found less often in IE patients with congenital heart disease (aOR = 0.20; 95% CI 0.04-0.99) and atypical pathogens isolated from blood culture (aOR = 0.31; 95% CI 0.14-0.72). CONCLUSIONS: Stroke is more likely to occur in individuals with systemic complications affecting other organs, too. Special attention should be addressed to dental status. The low incidence of stroke in patients with congenital heart disease may reflect awareness and prophylactic measures.

Peripheral endothelial function and arterial stiffness in women with migraine with aura: a case-control study.

BACKGROUND: Vascular dysfunction may be involved in migraine pathophysiology and contribute to the increased risk of ischemic stroke in migraine, particularly in women with migraine with aura (MA). However, data on endothelial function in MA are controversial. Here, we investigated whether systemic endothelial function and arterial stiffness are altered in women with MA, using a novel peripheral arterial tonometry device for the first time. METHODS: Twenty-nine female MA patients without comorbidities and 30 healthy women were included, and carotid intima-media thickness was assessed by a standardized procedure. Endothelial function was assessed using peripheral arterial tonometry. Reactive hyperaemic response of digital pulse amplitude was measured following 5 minutes of forearm occlusion of the brachial artery. Arterial stiffness was assessed by fingertip tonometry derived and heart-rate-adjusted augmentation index. RESULTS: No differences were found in peripheral arterial tonometry ratio (2.3 ± 0.6 vs 2.2 ± 0.8; p = 0.58) and left carotid intima-media thickness (in µm: 484 ± 119 vs 508 ± 60; p = 0.37). Women with MA had higher heart-rate-averaged augmentation index [median (interquartile range, IQR) of 5 (IQR 0.5 to 18) vs -5 (IQR -16.8 to 8.3), p = 0.005] and heart-rate-adjusted augmentation index [1 (IQR -6 to 12.5) vs -8 (IQR -20.3 to 2.5), p = 0.008] than healthy controls. CONCLUSION: Peripheral endothelial function is not impaired in women with MA, but they have greater arterial stiffness. This may contribute to the increased stroke risk in women with MA.

[Anemia and iron deficiency in the elderly. Prevalence, diagnostics and new therapeutic options]. / Anämie und Eisenmangel in der Geriatrie. Prävalenz, Diagnostik und neue Therapieoptionen.

The prevalence of anemia in geriatric patients is high. With some variation in different patient cohorts, prevalence of anemia can reach 40%. Anemia is not an age-related disease on its own, but is a symptom with multifactorial genesis and high risk potential. It directly influences mortality, morbidity, and the rate of hospitalization, particularly in older patients suffering from chronic heart failure or chronic kidney disease. The high prevalence of anemia in chronic kidney disease is explained by a combination of erythropoietin and iron deficiency. This review summarizes the recommendations of the iron symposium at the 2010 German Geriatric Society Meeting in Potsdam, Germany. It intends to provide current information on prevalence, diagnostic work-up, and therapeutic options for anemia in the rapidly growing group of elderly patients.

Impaired insulin sensitivity as an underlying mechanism linking hepatitis C and posttransplant diabetes mellitus in kidney recipients.

Aim of this study was to investigate the mechanism/s associating hepatitis C virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients. Twenty HCV-positive and 22 HCV-negative kidney recipients, 14 HCV-positive nontransplant patients and 24 HCV-negative nontransplant (healthy) subjects were analyzed. A 3-h intravenous glucose tolerance test was performed; peripheral insulin sensitivity was assessed by minimal modeling. Pancreatic insulin secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory cytokines in serum (tumor necrosis factor-alpha, intereukin-6, high-sensitive C-reactive protein) were also assessed. HCV-positive recipients showed a significantly lower insulin sensitivity as compared to HCV-negative recipients (3.0 +/- 2.1 vs. 4.9 +/- 3.0 min(-1).microU.mL(- 1).10(4), p = 0.02), however, insulin secretion and hepatic insulin uptake were not significantly different. Pancreatic antibodies were negative in all. HCV status was an independent predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The decrease of insulin sensitivity due to HCV was comparable for transplant and non-transplant subjects. No significant correlation was found between any of the cytokines and insulin sensitivity. Our results suggest that impaired peripheral insulin sensitivity is associated with HCV infection irrespective of the transplant status, and is the most likely pathogenic mechanism involved in the development of type 2 diabetes mellitus associated with HCV infection.

Models of sarcopenia: Short review.

Approximately 40-50% of the population over 80years of age suffers from sarcopenia making this condition a major geriatric clinical disorder and a key challenge to healthy aging. The hallmark symptom of sarcopenia is the loss of muscle mass and strength without the loss of overall body weight. Sarcopenic patients are likely to have worse clinical outcomes and higher mortality compared to healthy individuals. This review will focus on animal models designed to study sarcopenia including hind-limb unloading, de-nervation, and immobilization by using casts or wire strategies, as well as using aged rodents. Currently there are no registered treatments for sarcopenia. Most sarcopenic individuals show signs of physical frailty, which leads to increases the prevalence of balance disorders, falls, fractures and pain. Therefore, is it essential to develop and use relevant animal models to further the research on sarcopenia therapy?

The roles of immunity and autoimmunity in chronic heart failure.

Chronic heart failure (CHF) represents a major public health burden in developed countries. The introduction of new treatments has helped to improve its prognosis in recent years. However, it is still not possible to directly target the immunological aspects of the disease. In fact, chronic immune activation with the up-regulation of pro-inflammatory substances in the plasma remains an important feature of the disease, independently of its aetiology. Autoimmune mechanisms play a significant role in a subgroup of patients with dilated cardiomyopathy. The interplay between the two systems has not been established so far. This review briefly summarizes immune and autoimmune mechanisms in CHF.

Peripheral chemoreceptor hypersensitivity: an ominous sign in patients with chronic heart failure.

BACKGROUND: Peripheral chemoreceptor hypersensitivity is a feature of abnormal cardiorespiratory reflex control in chronic heart failure (CHF) and may contribute to sympathetic overactivity, attenuated baroreflex sensitivity (BRS), and excessive ventilation during exercise. We studied whether augmented peripheral chemosensitivity carries independent prognostic significance. METHODS AND RESULTS: We assessed peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalation of pure nitrogen) and BRS (phenylephrine and spectral methods) in 80 consecutive CHF patients (age 58+/-9 years; left ventricular ejection fraction [LVEF] 24+/-12%; peak oxygen consumption [peak VO(2)] 18+/-7 mL(-1). min(-1)). CHF patients demonstrated augmented peripheral chemosensitivity and decreased BRS (all P<0.01 versus reference values). During follow-up (median 41 months, >3 years in all survivors), 37 patients died. High peripheral chemosensitivity (>0.72 L. min(-1). %SaO(2)(-1)) predicted impaired survival (hazard ratio 3.2, 95% CI 1.6 to 6.0, P=0.0006). In the 27 patients (34%) with high peripheral chemosensitivity, 3-year survival was 41% (95% CI 22% to 60%) compared with 77% (66% to 89%) in 53 patients with normal chemosensitivity (P=0.0002). In multivariate analyses, augmented chemosensitivity independently predicted death (hazard ratio 2.8, 95% CI 1.5 to 5.5, adjusted for age, peak VO(2), and VE/VCO(2) [P=0.002]; hazard ratio 2.6, 95% CI 1.3 to 5.1, adjusted for age, LVEF, and peak VO(2) [P=0.008]). Depressed BRS was related to unfavorable prognosis in univariate analysis (P=0.05) but not in multivariate analyses. CONCLUSIONS: Hypersensitivity of the peripheral chemoreceptors independently predicts adverse prognosis in ambulatory patients with CHF. This hyperactive excitatory reflex, through its inhibitory effect on the baroreflex, may be the reason for the previously observed prognostic association of the latter.

Plasma cytokine parameters and mortality in patients with chronic heart failure.

BACKGROUND: Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients. METHODS AND RESULTS: In 152 CHF patients (age 61+/-1 years, New York Heart Association [NYHA] class 2.6+/-0.1, peak VO(2) 17.3+/-0.6 mL. kg(-1). min(-1), mean+/-SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (>12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-alpha, sTNF-R1, and sTNF-R2 (all P

Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone.

OBJECTIVES: We aimed to determine whether growth hormone (GH) resistance is present in patients with chronic heart failure (CHF) and whether it may be linked to the biochemical response to GH treatment. BACKGROUND: Acquired GH resistance is a feature of severe illness, in particular, cachexia. In patients with CHF, the response to GH therapy appears to be variable. METHODS: Biochemical markers of the GH-insulin-like growth factor-I (IGF-I) axis were compared in 21 cachectic patients with CHF, 51 noncachectic patients and 26 healthy control subjects. In separate studies, the predictive value of baseline biochemical variables for the IGF-I response to GH treatment was analyzed. RESULTS: Cachectic patients showed an increase of total GH and immunologically intact GH (p < or = 0.0002) and a decrease of GH-binding protein (BP) (p = 0.005), IGF-BP3 (p = 0.01) and IGF-I (p = 0.06), compared with noncachectic patients. Similar changes were found when the cachectic group was compared with the control group. No differences were found between noncachectic patients and control subjects. Levels of GH-BP correlated with the IGF-I/GH ratio in all subgroups (all p < or = 0.002). Baseline GH-BP levels were related to the increase of IGF-I levels in response to GH treatment in patients with CHF after 24 h (r = 0.83, p = 0.005; n = 9; study 2), 44 days (r = 0.52, p = 0.007; n = 25; study 3) and 96 days (r = 0.54, p = 0.006; n = 24; study 3). CONCLUSIONS: Most cachectic and some noncachectic patients with CHF show features of acquired GH resistance. The principal predictors of the biochemical features of GH resistance and of the poor biochemical response to short-term and longer-term GH treatment are GH-BP plasma levels. The presence of GH resistance is potentially a major factor determining the response to GH therapy in patients with CHF.

Anemia in chronic heart failure--clinical and prognostic significance.

Anemia is a common finding in chronic heart failure (CHF). Anemia develops due to CHF, but is also known to cause heart failure. Patients with CHF are limited by exercise capacity and fatigue. Low hemoglobin concentration can account for both and may substantially contribute to the symptoms of CHF. Increasing severity of CHF is associated with a higher frequency of anemia, which also becomes clinically more relevant. Anemia has been shown to predict impaired survival in CHF, independent of established prognostic markers. There are many potential reasons for development of anemia in CHF, such as bone marrow depression, reduced intestinal iron uptake and hemodilution as a consequence of sodium and water retention. In most cases, however, anemia in CHF should be viewed as "anemia of chronic illness", being the result of a combination of many factors related to the disease, particularly chronic inflammation. The option of therapeutically targeting anemia in CHF is an intriguing novel approach to improve morbidity and potentially mortality in these patients.

Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.

Blood loss and bleeding complications may often be observed in critically ill patients on renal replacement therapies (RRT). Here we investigate procedural (i.e. RRT-related) and non-procedural blood loss as well as transfusion requirements in regard to the chosen mode of dialysis (i.e. intermittent haemodialysis [IHD] versus continuous veno-venous haemofiltration [CVVH]). Two hundred and fifty-two patients (122 CVVH, 159 male; aged 61.5±13.9 years) with dialysis-dependent acute renal failure were analysed in a sub-analysis of the prospective randomised controlled clinical trial-CONVINT-comparing IHD and CVVH. Bleeding complications including severity of bleeding and RRT-related blood loss were assessed. We observed that 3.6% of patients died related to severe bleeding episodes (between group P=0.94). Major all-cause bleeding complications were observed in 23% IHD versus 26% of CVVH group patients (P=0.95). Under CVVH, the rate of RRT-related blood loss events (57.4% versus 30.4%, P=0.01) and mean total blood volume lost was increased (222.3±291.9 versus 112.5±222.7 ml per patient, P <0.001). Overall, transfusion rates did not differ between the study groups. In patients with sepsis, transfusion rates of all blood products were significantly higher when compared to cardiogenic shock (all P <0.01) or other conditions. In conclusion, procedural and non-procedural blood loss may often be observed in critically ill patients on RRT. In CVVH-treated patients, procedural blood loss was increased but overall transfusion rates remained unchanged. Our data show that IHD and CVVH may be regarded as equivalent approaches in critically ill patients with dialysis-dependent acute renal failure in this regard.

Validation of the FEW16 questionnaire for the assessment of physical well-being in patients with heart failure with reduced ejection fraction: results from the CIBIS-ELD study.

AIMS: Patients with heart failure (HF) commonly suffer from severe impairment of quality of life (QoL). One main goal of HF treatment is improvement of QoL. Physical well-being is an essential component of QoL. To enable assessment of physical well-being in HF patients, we validated the FEW16 questionnaire in a prospective study with patients from the Cardiac Insufficiency Bisoprolol Study in ELDerly. METHODS AND RESULTS: In 127 HF patients (age 73 ± 5.5 years, 72% male, 60% New York Heart Association class II, left ventricular ejection fraction 37 ± 8.5%), we measured physical well-being (FEW16), QoL [36-Item Short-Form Health Survey (SF36)], and depressive symptoms [PRIME MD Patient Health Questionnaire German short version for depression (PHQ-D)] at baseline and two follow-up visits, and correlated FEW16 scores with QoL data and clinical parameters. FEW16 mean scores are 3.04 ± 1.04 at baseline, 3.19 ± 0.94 after 3 months, and 2.77 ± 0.94 after 2-4 years. We assessed data quality, scale assumptions, and construct validity and reliability. Cronbach's alpha for subscales resilience: 0.84; ability to enjoy: 0.80; vitality: 0.88; inner peace: 0.87; total score: 0.95. Intraclass correlation coefficient (ICC) is 0.87 (95% CI 0.84-0.89, ICC (1.4). Pearson's correlations of FEW16 with SF36 and PHQ-D were significant. Six minutes walking distance and heart rate correlated significantly with the FEW16 total score. CONCLUSIONS: The FEW16 showed good reliability, internal consistency, and intraclass correlation. FEW16 scores correlated well with psychological and physical well-being (SF36) and clinical markers of exercise tolerance (6 min walk test and heart rate). Our results indicate a strong correlation of self-reported physical well-being with psychological factors. FEW16 values at baseline predicted the development of several aspects of QoL during beta-blocker up-titration.

Echocardiographic determinants of mortality in patients >67 years of age with chronic heart failure.

This study sought to assess the prognostic significance of echocardiographic measurements of left and right ventricular dimensions and function in patients >67 years of age with chronic congestive heart failure (CHF). This is a retrospective follow-up of elderly patients who underwent an echocardiography in the tertiary cardiac center. A total of 185 patients (131 men) aged >/=68 years (mean +/- SD 75 +/- 5) with CHF were enrolled into the study. After undergoing a detailed echocardiographic examination, all patients were followed-up for a median of 20 months (interquartile range 9 to 36). During the follow-up period 54 patients (29%) died. Left ventricular (LV) M-mode isovolumic relaxation time (IVRT), end-diastolic and end-systolic diameters, fractional shortening and mass, transmitral E:A ratio, and left atrial dimension, as well as New York Heart Association class and the age were found by Cox proportional-hazards univariate analyses to predict the outcome in these patients (all p <0.05). In multivariate analyses including these measurements, LV IVRT (p <0.04), age (p <0.03), and New York Heart Association class (p <0.001) were found to be the independent predictors of outcome. In the Kaplan-Meier analysis, patients with LV IVRT >30 ms had a better prognosis at 3 years (cumulative survival 78% [95% confidence interval 65% to 91%]) than those with LV IVRT 67 years of age with CHF. LV M-mode IVRT is among the most important independent predictors of outcome in this population.

Leptin, insulin sensitivity and growth hormone binding protein in chronic heart failure with and without cardiac cachexia.

OBJECTIVE: Regulation of growth hormone (GH) receptor expression and hence tissue GH sensitivity may be important for the conflicting results found in treatment studies with recombinant growth hormone in chronic heart failure (CHF). Growth hormone-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor and is closely related to measures of body composition and, specifically, to size of visceral fat tissue. Leptin, the adipocyte specific (ob) gene product, has been proposed as the signal linking adipose tissue and GHBP/GH-receptor expression. CHF has recently been shown to be a hyperleptinaemic and insulin-resistant state regardless of aetiology. This study aimed to examine the influence of leptin on GHBP in CHF patients with and without cardiac cachexia compared with healthy control subjects. METHODS: We studied 47 male patients with CHF (mean age 61+/-2 years, New York Heart Association (NYHA)-class 2.7+/-0.1, left ventricular ejection fraction (LVEF) 28+/-2%, peak oxygen consumption 16.8+/-0.9 ml/kg/min) and 21 male healthy controls of similar age. Of the CHF patients, 19 were cachectic (cCHF; non-oedematous weight loss >7.5% over at least 6 months) and 28 non-cachectic (ncCHF; similar for age and LVEF). Insulin sensitivity was assessed by an intravenous glucose tolerance test using the minimal model approach. RESULTS: Compared with healthy controls, patients had elevated levels of leptin (7.6+/-0.7 vs 4.8+/-0.7 ng/ml, P<0.05), insulin (76.2+/-8.9 vs 41.4+/-6.0 pmol/l, P<0.01), and reduced insulin sensitivity (2.43+/-0.2 vs 3.48+/-0.3 min(-1).microU.ml(-1).10(4), P<0.005) but similar GHBP levels (901+/-73 vs 903+/-95 pmol/l). Leptin levels were increased in ncCHF (9.11+/-1.0 ng/ml, P=0.001) but were not different from normal in cCHF (5.32+/-0.7 ng/ml, P>0.5). After correction for total body fat mass, both ncCHF and cCHF were hyperleptinaemic (41.8+/-3.8 and 37.9+/-0.38 vs 24.4+/-2.1 ng/ml/100 g, ANOVA P=0.001). In both patients and controls there was a direct correlation between leptin levels and GHBP (r=0.70 and r=0.71 respectively, both P<0.0001). This relationship was stronger than between GHBP and several parameters of body composition (body mass index (BMI), total and regional body fat mass or % body fat) and held true when sub-groups were tested individually (ncCHF r=0.62, P<0.001; cCHF r=0.79, P<0.0001). In multivariate regression analysis in all CHF patients, serum leptin levels emerged as the strongest predictor of GHBP, independent of age, BMI, total and regional fat mass or % body fat, fasting insulin level and insulin sensitivity. CONCLUSION: Fat mass corrected leptin levels are elevated in CHF patients with and without cachexia. Reduced total fat mass may account for lower leptin levels in cachectic CHF patients compared with non cachectic patients. Leptin strongly predicts GHBP levels in CHF regardless of its hyperleptinaemic state or severely altered body composition as in cardiac cachexia. Leptin could be the signalling link between adipose tissue and GHBP/GH receptor expression in CHF.

Anemia in chronic heart failure--frequency and prognostic impact.

Chronic heart failure (CHF) is an important public health care problem and a leading cause of morbidity and mortality world wide. Anemia is a common finding in CHF and known to cause heart failure. Patients with CHF are limited by exercise capacity and fatigue. A low hemoglobin concentration leads to impairment of both. With increasing severity of heart failure, anemia also becomes more frequent and clinically more relevant. There are many potential reasons for development of anemia in chronic heart failure like bone marrow depression, reduced intestinal iron uptake, and the dilution in consequence of sodium and water retention. However, the anemia seen in CHF is generally an "anemia of chronic illness". Furthermore, it has been shown that hemoglobin levels independently predict increased mortality in CHF.

Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeutic effect of allopurinol.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide-dependent vasodilation. In 113 patients with chronic heart failure (CHF) and 26 controls, ADMA level was studied in relation to peripheral blood flow and vasodilator capacity. Further, the effects of allopurinol on concentrations of reactive oxygen species (ROS) and ADMA and peripheral vasodilator capacity were tested in a double-blind design. ADMA level was found to be elevated in CHF patients as compared with controls and increased in parallel with New York Heart Association (NYHA) class and exercise capacity (all P < 0.0001). The level of ADMA predicted resting blood flow (P < 0.05) and postischemic vasodilator capacity (P < 0.001). Sixty eight patients died during the follow-up period. The level of ADMA predicted survival after multivariable adjustment (P = 0.04). Allopurinol reduced uric acid (UA) concentration (P < 0.001) and decreased ROS concentration (allantoin, P < 0.01). Allopurinol lowered ADMA concentration (P = 0.02); postischemic vasodilation as well as endothelium-dependent vasodilation (both P < 0.05) improved. ADMA may be a pathophysiologic factor that is modulated by ROS accumulation and contributes to impaired vascular regulation in CHF.