Pro-inflammatory cytokines and endothelium-dependent vasodilation in the forearm. Serial assessment in patients with congestive heart failure

Background In patients with heart failure endothelium-dependent vasodilationof the forearm conduit vessels is impaired possibly becauseof elevated plasma levels of pro-inflammatory cytokines. Theeffect of elevated plasma cytokines on endothelium-dependentvasodilation of forearm conduit vessels was therefore seriallyinvestigated in 16 patients with congestive heart failure duringan episode of acute failure and at the time of recompensation. Methods and Results Pro-inflammatory cytokine levels and hyperaemic brachial arterydiameters were obtained shortly after admission for an episodeof acute heart failure and 11±3 days later at the timeof recompensation, which was obtained using diuretic therapywithout changing other cardiovascular medications. Serum concentrations(Mean±SD) of tumour necrosis factor alpha (TNF-) (decompensationvs recompensation: 25±23pg.ml^–1vs 26±17pg.ml^–1)and interleukine 6 (IL-6) (decom-pensation vs recompensation:27±24pg.ml^–1vs 20±18pg.ml^–1), determinedin venous blood using immunoradiometric assays were elevatedbut remained unaltered following recompensation. Brachial arterydiameter, derived from high-resolution ultrasound scans at restand during reactive hyperaemia, 90s after forearm cuff deflation,increased significantly during reactive hyperaemia at the timeof admission (3·4±0·7mm vs 4·0±0·5mm;P=0·014)and following recompensation (3·4±0·5mmvs 3·8±0·2mm;P=0·032). The brachialartery diameter during recompensation expressed as a percentageof the baseline value was similar at both intervals (decompensationvs recompensation: 117±14% vs 116±10%;P=ns). Atthe time of decompensation, the correlation between TNF- andthe percentage change in brachial artery diameter followingreactive hyperaemia was absent (r=0·098;P=0·719).The same correlation became significant at the time of recompensation(r=0·750;P=0·001). Conclusions In patients with congestive heart failure, plasma levels ofpro-inflammatory cytokines correlate with endothelium-dependentvasodilation of the brachial artery following recompensation,but not during an acute episode of heart failure.     

Relationship between cytokines and tumour markers in patients with chronic heart failure

AIMS: Serum levels of some cytokines and tumour markers are elevated in patients with chronic heart failure (HF). We aimed to investigate the relationship between circulating levels of cytokines and tumour markers in patients with HF. METHODS: We included 35 HF patients and 33 normal controls. HF patients were divided into two groups: mild HF (NYHA class I/II) (n=10) and severe HF (NYHA class III/IV) (n=25). Serum cytokine levels (TNF-alpha, IL-1 beta, IL-6, and IL-10) were measured by ELISA and tumour markers (CA 125, CA 19-9, CA 15-3, CEA and AFP) by chemiluminescent enzyme immunoassay. RESULTS: Serum levels of TNF-alpha, IL-6, and IL-10 as cytokines, and CA 125 and CA 19-9 as tumour markers were significantly higher in HF patients than in normal controls (p<0.0001 for all). Serum levels of TNF-alpha, IL-6 and IL-10 and CA 125 in the severe HF patients were significantly higher than in the mild HF patients (p<0.001 for all). Correlation analysis showed that CA 125 was positively related to TNF-alpha (r=0.624, p<0.001), IL-6 (r=0.671, p<0.001), and IL-10 (r=0.545, p<0.001) in HF. CONCLUSION: These findings show that CA 125 is markedly elevated in patients with HF, and correlates with serum TNF-alpha, IL-6 and IL-10 levels. Therefore, we speculate that among the tumour markers studied, only CA 125 is closely related to the cytokine system.     

Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or 14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.     

Correlation between serum levels of microRNA-21 and inflammatory factors in patients with chronic heart failure

As the leading cause of hospitalization and mortality worldwide, heart failure (HF) has caused significant burden on both individuals and the whole society. Thus, increasing knowledge about the phytopathology of HF is in demand for both diagnosis and treatment. Previous studies have shown that both microRNA 21 (miRNA-21) and inflammatory factors are closely related to the development of cardiac fibrosis, hypertrophy, and HF. However, whether there is any crosstalk between the 2 has not been examined. The current study evaluated the correlation between serum levels of miRNA-21 and critical inflammatory factors during the progress of chronic heart failure (CHF), providing new insights in understanding the physiopathology of CHF and identifying CHF biomarkers. In the presented study, serum level of miR-21, cardiac neurohormone, and critical inflammatory factors were measured and compared on 120 (67 male/53 female) CHF patients and 100 (58 male/42 female) health people with non-failing hearts. Echocardiography was also conducted to assess the severity of CHF. Correlations between different factors were calculated and tested for statistical significance. From our results, CHF patients showed significantly decreased serum levels of miR-21 while increased levels of inflammatory factors and cardiac neurohormone (P < .05). Levels of miR-21 negatively correlate with cardiac function while positively correlates with myocardial remodeling (P < .05). Levels of miR-21 negatively correlate with inflammation in CHF (P < .05). These findings indicate the potential crosstalk between serum miR-21 and inflammation during CHF progression, suggesting the potential of miR-21 in CHF diagnosis, severity indication, and treatment.     

A glossary of circulating cytokines in chronic heart failure

Recent studies have emphasized the importance of biologically active molecules, termed cytokines, in the development and progression of the syndrome of chronic heart failure. This article summarizes a glossary of major cytokines and other cytokine-related inflammatory factors implicated in the pathophysiology of chronic heart failure, describing the source of their synthesis and factors regulating their secretion and analyzing their biologic effects on the cardiovascular system.     

男性心力衰竭患者血清雄激素与细胞因子及活化蛋白的关系

目的探讨男性心力衰竭(心衰)患者血清雄激素与细胞因子及活化蛋白(activator protein-1,AP-1)的关系。方法选择160例男性心衰患者作为心衰组,心功能(NYHA)Ⅱ级40例,Ⅲ级55例,Ⅳ级65例,同期选择40例健康体检男性作为对照组,ELISA法检测外周血游离睾酮(FT)、总睾酮(TT)、去氢表雄酮(DHEA)、去氢表雄酮硫酸酯(DHEAS),白细胞介素(IL)-1β、IL-6、TNF-α、IL-10及AP-1的水平,进行相关分析。结果心衰组血清FT[(42.76±8.46)pmol/L vs(51.25±4.71)pmol/L]、TT[(14.26±3.65)nmol/L vs(17.98±2.59)nmol/L]、DHEA[(6.63±1.43)nmol/Lvs(6.39±1.39)nmol/L]、DHEAS[(1.77±0.59)nmol/Lvs(2.28±0.43)nmol/L]及IL-10水平显著低于对照组,随心功能Ⅱ级、Ⅲ级到Ⅳ级增加逐级显著下降(P<0.05,P<0.01)。心衰组血清IL-1β、IL-6、TNF-α、AP-1水平显著高于对照组,由心功能Ⅱ级、Ⅲ级到Ⅳ级增加而逐级显著升高(P<0.05,P<0.01)。心衰组FT、TT、DHEA、DHEAS与IL-1β、IL-6、TNF-α、AP-1呈负相关(P<0.05,P<0.01),与IL-10呈正相关(P<0.05,P<0.01);FT与AP-1独立负相关(P<0.01)。结论男性心衰患者血清雄激素水平减低,可能与致炎细胞因子增高、抗炎细胞因子减少及AP-1活化有关,低雄激素血症影响男性心衰的发生和发展。     

急性肝衰竭患者血清炎性细胞因子水平分析

目的：探讨急性肝衰竭患者血清炎性细胞因子水平的变化。方法选择15例急性肝衰竭患者和15例健康人,采用Cytometric Bead Array法检测血清细胞因子。结果急性肝衰竭患者和健康人血清IL-2、IL-4、IL-5、IL-12p70和TNF-β水平无统计学差异;急性肝衰竭患者血清TNF-α（13.49 pg/mL）、IL-6（480.96 pg/mL）、IL-10（330.28 pg/mL）和IL-17（6.36 pg/mL）水平显著高于健康人（TNF-α为7.32 pg/mL,P=0.03;IL-6为4.64 pg/mL,P＆lt;0.01;IL-10为5.47pg/mL,P＆lt;0.01;IL-17为2.03 pg/mL,P=0.04）。结论炎性细胞因子在急性肝衰竭发病的病理过程中可能起了重要作用。     

Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure

INTRODUCTION: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF-alpha levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.     

Epidemiology of acute heart failure syndromes

Acute Heart Failure is a heterogeneous set of syndromes associated with significant morbidity and mortality. There are several classifications of acute heart failure syndromes (AHFS) based on pathophysiology or clinical presentation. In the USA and in Europe, AHFS are the first cause of hospitalization of the elderly, and the leading health care cost. Despite this clinical and social importance, AHFS have received little attention from clinicians and researchers. Recently published epidemiological studies described clinical presentation, characteristics and treatment of over 100,000 patients hospitalized with AHFS. These studies also underlined the poor, short, and medium term prognosis, especially for the most severe patients admitted to an intensive care unit, with in-hospital mortality of 28%. Further epidemiological and clinical research is needed to improve our understanding of AHFS, thereby enhancing patient care.     

Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.     

左西孟旦在老年急性左心衰竭患者中的应用

目的评价左西孟旦治疗老年急性左心衰竭的临床疗效。方法选取2011年6月至2013年6月在第四军医大学西京医院老年病科住院的急性左心衰竭患者72例,其中男49例、女23例,年龄65～87（75.1±9.8）岁。将其随机分为对照组和左西孟旦组（n＝36）,对照组给予常规抗心力衰竭治疗,左西孟旦组在常规抗心力衰竭治疗的基础上加用左西孟旦。观察两组患者的临床疗效、每搏心输出量（SV）、左室射血分数（LVEF）及N-末端脑钠肽前体（NT-pro-BNP）的改善情况。结果治疗后两组患者的心力衰竭症状和体征均有显著改善。SV及LVEF明显提高（P＜0.05）,NT-pro-BNP下降明显（P＜0.05）。左西孟旦组的总有效率显著高于对照组（94.4% vs 69.4%,P＜0.05）。与对照组比较,左西孟旦治疗组SV及LVEF显著提高（P＜0.05）,NT-pro-BNP下降更明显（P＜0.05）。结论左西孟旦注射液治疗老年急性左心衰竭患者疗效确切,安全性好。     

Reduced immune responses to an aseptic inflammation in mice with congestive heart failure

We previously found that mice with congestive heart failure (CHF) were anemic, had decreased bone marrow haematopoiesis and functionally impaired neutrophilic granulocytes despite normal blood concentrations of these cells. We now asked if CHF-mice could mount an adequate immune response when challenged with an acute inflammation. A postinfarction heart failure was induced in mice. Six weeks later the mice had developed CHF. At that time a sterile peritonitis was induced by injection of a casein digest. Five hours after this injection a marked neutrophilia had developed. Specimens were then obtained from peritoneal washings, bone marrow and blood. Total bone marrow cell numbers were halved in CHF-peritonitis mice compared with sham-peritonitis mice. Bone marrow colony-forming cell numbers in CHF-peritonitis mice were only 14% of those in sham-peritonitis mice. The mobilization of leucocytes to the blood was much lower in CHF-peritonitis mice than in sham-peritonitis mice (5.6 vs. 8.1 million cells/mL), as was the peritoneal influx of these cells (1.6 vs. 4.1 million cells). A profound decline (>50%) in the functional activity, determined with various in vitro assays, was evident for both neutrophilic granulocytes and lymphocytes from CHF-peritonitis mice. Heart failure after myocardial infarction in mice may severely compromise their ability to combat an inflammatory challenge.     

老年慢性心力衰竭患者细胞因子和心率变异性的相关性研究

目的 观察老年慢性心力衰竭(CHF)患者炎性细胞因子和心率变异性(HRV)的相关性.方法 128例60岁及以上老年CHF患者(CHF组),对照组50例为健康体检者.比较两组炎性细胞因子包括肿瘤坏死因子可溶性受体Ⅰ、Ⅱ(sTNF-RⅠ、sTNF-RⅡ)和白细胞介素6(IL-6)表达水平,24 h内的全部HRV参数[正常心动周期的标准差(SDNN)、24 h内5 min节段平均心动周期的标准差(SDANN)、24 h内全部5 min节段所有心动周期标准差的平均值(SDNNI)、相邻正常心动周期差值均方的平均根(rMSSD)和相邻两正常心动周期差值大于50 ms的个数所占的百分比(pNN50)],分析二者相关性.结果 CHF组患者HRV参数低于对照组:SDNN分别为(99.8±22.4)和(146.6±43.2)ms、SDANN分别为(85.5±23.6)和(138.7±40.9)ms、SDNNI分别为(41.7±15.8)和(56.9±18.8)ms、rMSSD分别为(23.4±13.0)和(30.0±12.9)ms、pNN50分别为(5.5±3.8)和(12.0±4.7)%;CHF患者炎性细胞因子明显高于对照组(均为P＜0.05);CHF患者HRV参数与炎性细胞因子浓度间呈负相关(r≥-0.44,P＜0.05).结论 炎性细胞因子sTNF-R Ⅰ、sTNF-RⅡ和IL-6可能是老年CHF患者HRV下降的原因之一.     

Quantification of proinflammatory cytokines in the urine of congestive heart failure patients. Its relationship with plasma levels

AIMS: Proinflammatory cytokines are important mediators for the development of heart failure and increased plasma levels of these cytokines have been reported in patients with this condition. The purpose of the study was to investigate whether urine, a non-invasively obtained biological sample, was an appropriate medium in which to measure the concentration of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in patients in the advanced stages of the disease. METHODS AND RESULTS: Thirty consecutive patients who had severe congestive heart failure (NYHA classes III and IV) and 30 matched healthy control subjects were enrolled. Plasma and the first urine of the day were collected and TNF-alpha and IL-6 were quantitatively analyzed by enzyme-linked immunosorbent assays. For every subject there were no differences in the amount of cytokine determined in plasma and urine. Both urine and plasma levels of IL-6 and TNF-alpha were greater in heart failure patients than in controls. CONCLUSION: Our results show that plasmatic and urinary levels of proinflammatory cytokines did not differ significantly. Thus, urine may be a good milieu in which to study these cytokines and may have diagnostic, prognostic and therapeutic implications.     

急性心力衰竭综合病因评分预计死亡率研究

目的 探讨急性心力衰竭病因评分在急性心力衰竭疾病中的应用价值.方法 采用APACHEⅡ评分、心力衰竭基础病因及诱因综合评分,在此评分基础上对42 例急性心力衰竭患者预计死亡率进行评估并建立预计死亡率模型,分层计算群体预计死亡率.结果 根据急性心力衰竭病因评分分值进行分组,随着分值逐渐升高,实际病死率和预计死亡率也逐渐升高,死亡组评分均值显著高于生存组(P＜0.05).结论 急性心力衰竭病因评分系统简易实用,可用于院前急救及急诊急性心力衰竭患者初步评估.     

Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure

BACKGROUND: Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF). AIM: To evaluate the prognostic role of inflammatory cytokines in patients with ADHF. METHODS: Levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 423 patients with ADHF. In addition, appropriate cytokine gene polymorphisms were determined. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS: Elevated levels of IL-6 and TNF-alpha were strongly associated with increased 12-month mortality (P<0.001 for both), whereas the level of IL-10 was predictive only of 6-month mortality (P<0.01). In multivariate analysis IL-6, chronic renal insufficiency, NT-proBNP, age/10 years' increase and TNF-alpha were identified as the most powerful predictors of 12-month mortality. Furthermore, high levels of both IL-6 and NT-proBNP were associated with >7-fold mortality. Cytokine gene polymorphisms were not associated with outcome. CONCLUSIONS: Circulating levels of pro-inflammatory cytokines IL-6 and TNF-alpha, and the level of an anti-inflammatory cytokine IL-10, but not their gene polymorphisms, provide novel and important prognostic information in patients with ADHF. Combining measurements of pro-inflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients.     

Pulmonary endothelium as a site of synthesis and storage of interleukin-6 in experimental congestive heart failure

BACKGROUND: Pulmonary endothelium is an early upstream hemodynamic target of left ventricular dysfunction. Interleukin 6 (IL-6) is a pro-inflammatory cytokine reported to increase in congestive heart failure (CHF) patients. AIMS: We sought to determine the origin of IL-6, IL-6 receptor (IL-6R) and gp130 in experimental CHF. METHODS: We used rats with coronary artery ligation as an experimental model of either compensated or decompensated heart failure. Lung and aorta samples were analysed by RT-PCR, ELISA and immunohistochemistry for IL-6 and its receptors. RESULTS: IL-6 mRNA expression increased in the lung of rats with decompensated heart failure and was positively correlated with infarct severity whereas IL-6R mRNA decreased in the lung of myocardial infarction rats and gp130 mRNA remained unchanged. In contrast, there were no changes in IL-6 mRNA expression in the aorta and left ventricular myocardium. IL-6 peptide content as determined by ELISA and Western Blot in lung tissue was 2-fold higher in decompensated heart failure as compared to control rats. These data were confirmed by immunohistochemistry showing a preferential endothelial localization of IL-6 in the CHF lung. IL-6 peptide was also present in the pleural effusion of decompensated heart failure and was positively correlated with IL-6 mRNA expression in the lungs of decompensated HF rats. Pulmonary IL-6 overexpression was associated with nuclear translocation of NF-kappaB and cytosolic degradation of IkappaB. CONCLUSION: Dysfunctional pulmonary endothelium is a source of synthesis and storage of IL-6 in an experimental model of CHF.     

Invasive hemodynamic assessment in heart failure

Routine cardiac catheterization provides data on left heart, right heart, systemic and pulmonary arterial pressures, vascular resistances, cardiac output, and ejection fraction. These data are often then applied as markers of cardiac preload, afterload, and global function, although each of these parameters reflects more complex interactions between the heart and its internal and external loads. This article reviews more specific gold standard assessments of ventricular and arterial properties, and how these relate to the parameters reported and utilized in practice, and then discusses the re-emerging importance of invasive hemodynamics in the assessment and management of heart failure.     

Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure

BACKGROUND: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF-alpha and IL-6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 initiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest. METHODS: Fifty patients with CHF (aged 66.9+/-12.6 years, mean ejection fraction 22.1+/-9.2%, NYHA II-IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5+/-9.8 years) were examined. Thirty-two patients were taking aspirin (100 mg/day). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti-CD154, anti-P-selectin, and anti-CD61 and thereafter analyzed by flow cytometry. RESULTS: Patients with CHF showed significantly enhanced expression of platelet-bound CD154 and P-selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity [MFI], P<0.001; P-selectin: median 3.2 25th percentile: 1.9; 75th percentile: 5.9 vs. 1.4; 25th: 1.2; 75th: 1.9, MFI, P<0.001). CD154 expression on platelets positively correlated with increasing NYHA-class. In contrast, no significant differences in serum levels of soluble CD154 or CD40 expression on monocytes were detected in the study groups. Antiplatelet-therapy with aspirin did not influence CD154 or P-selectin expression on platelets. CONCLUSION: Our pilot study demonstrates significantly enhanced levels of CD154 on platelets in patients with CHF. This suggests that the CD40-CD154 axis may contribute to the proinflammatory milieu, which exists in CHF and thus may play a pathogenic role in the development and progression of CHF.