Soluble CD40 ligand, platelet surface CD40 ligand, and total platelet CD40 ligand in atrial fibrillation: relationship to soluble P-selectin, stroke risk factors, and risk factor intervention

BACKGROUND: Abnormal levels of soluble CD40 ligand (sCD40L) have been reported in patients with hypertension, coronary artery disease, diabetes mellitus, heart failure, and stroke, all of which are conditions that are associated with nonvalvular atrial fibrillation (AF). We hypothesized the following: (1) CD40 ligand (CD40L)-related indexes (ie, platelet surface expressed CD40L, the soluble fragment of CD40L [sCD40L], and the total amount of CD40L per platelet [pCD40L]) are elevated in patients with AF compared to control subjects; (2) these indexes correlate with soluble P-selectin (sP-selectin), which is an established platelet marker; and (3) these indexes differentiate "high-risk" from "low-risk" subjects. METHODS: We performed a case-control study of 121 AF patients, 71 "disease control subjects," and 56 "healthy control subjects." Peripheral venous levels of platelet surface-expressed CD40L were analyzed by flow cytometry, while levels of sCD40L, pCD40L, and sP-selectin were measured by enzyme-linked immunosorbent assay. RESULTS: AF patients had significantly higher sCD40L levels compared to healthy control subjects (p = 0.042), with no difference in platelet surface CD40L and pCD40L levels. A positive correlation was noted between levels of sCD40L and pCD40L, and not with sP-selectin. CD40L-related indexes failed to distinguish between high-risk and low-risk AF patients. AF patients receiving optimal antithrombotic therapy had significantly lower pCD40L levels (p < 0.001) compared to control subjects. Optimized AF management also resulted in significant reductions in the levels of sCD40L (p = 0.023) and pCD40L (p < 0.001). CONCLUSION: CD40L-related indexes are not useful in the risk stratification of AF patients, and abnormal sCD40L levels can be reduced by intense multifactorial risk management. While there is a significant, albeit modest, excess of platelet activation in AF patients (as measured by sCD40L levels) compared to healthy control subjects, this is not in excess of that seen in patients with underlying cardiovascular diseases.     

Effect of clopidogrel discontinuation at 1?year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study

Antiplatelet therapy with clopidogrel has been shown to reduce major adverse cardiac events in acute coronary syndromes and after percutaneous interventions. This effect is not only due to its anti-platelet effect but also possibly due to an anti-inflammatory effect. The effect of clopidogrel cessation after one year of therapy on markers of inflammation has been investigated in diabetics and showed an increase in platelet aggregation as well as hsCRP and surface P-selectin levels. This was an exploratory multicenter prospective open-label single arm study of 98 non-diabetic patients who had received one or more drug eluting stents and were coming to the end of their 12 months course of clopidogrel therapy. The effect of clopidogrel cessation on expression of biomarkers: sCD40L, soluble P-selectin and hsCRP was measured right before clopidogrel cessation (day 0), and subsequently at 1, 2, 3 and 4 weeks after drug withdrawal. A median increase in sCD40L expression from 224 to 324.5 pg/ml was observed between baseline and 4 weeks after clopidogrel cessation, which corresponded to a 39% mean percent change based on an ANCOVA model (P < 0.001). Over the 4 weeks observation period the change in sCD40L expression correlated weakly with soluble P-selectin levels (at 4 weeks Spearman’s correlation coefficient = 0.32; P = 0.0024). Increase in P-selectin expression from baseline was statistically significant at week 1 and 2. Conversely, hsCRP level decreased by 21% at 1 week (P = 0.008) and was still reduced by 18% by 4 weeks (P = 0.062). The change in sCD40L expression appeared to vary with the type of drug eluting stent. Patients treated with drug eluting stents at 1 year after implantation display significant increase in sCD40L and decrease in hsCRP after clopidogrel cessation. Further studies should elucidate if this increase in sCD40L levels reflects solely the removal of the inhibitory effects of clopidogrel on platelet activity or rather an increase in pro-inflammatory state. The latter hypothesis may be less likely given decrease in hsCRP levels. Randomized studies are urgently needed to establish potential link of clopidogrel discontinuation and vascular outcomes.     

Silent brain infarction and platelet activation in obstructive sleep apnea

RATIONALE: Silent brain infarction (SBI) and increased levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) are associated with an increased risk of cerebrovascular disease. OBJECTIVES: The aim of this study was to evaluate whether SBI and serum levels of sCD40L and sP-selectin are increased in patients with obstructive sleep apnea (OSA). METHODS: SBI was studied by brain magnetic resonance images in 50 male patients with OSA and 15 obese male control subjects who were free of comorbidities. In addition, the effects of 3 months of treatment with nasal continuous positive airway pressure (nCPAP) on serum parameters were studied in 24 patients with moderate to severe OSA. MEASUREMENTS AND MAIN RESULTS: The percentage of SBI in patients with moderate to severe OSA (25.0%) was higher than that of obese control subjects (6.7%) or patients with mild OSA (7.7%). Serum levels of sCD40L and sP-selectin were significantly higher in patients with moderate to severe OSA than in obese control subjects (p < 0.05) or patients with mild OSA (p < 0.05). In addition, nCPAP significantly decreased serum levels of sCD40L (p < 0.03) and sP-selectin (p < 0.01) in patients with moderate to severe OSA. CONCLUSIONS: These results suggest that serum levels of sCD40L and sP-selectin are elevated and SBI is more common in patients with moderate to severe OSA, leading to elevated cerebrovascular morbidity. Moreover, nCPAP may be useful for decreasing risk in patients with moderate to severe OSA.     

Soluble P-selectin and CD40L levels in subjects with prediabetes, diabetes mellitus, and metabolic syndrome--the Chennai Urban Rural Epidemiology Study

The aim of the study was to determine whether the levels of soluble P-selectin (sP-selectin) and soluble CD40L (sCD40L) are elevated in Asian Indian subjects with impaired glucose tolerance (IGT), diabetes, and metabolic syndrome (MS). Study subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing population-based study on a representative population of Chennai city in southern India, and were grouped as follows: group 1, normal glucose tolerance (NGT) (n = 60); group 2, IGT (n = 60); and group 3, type 2 diabetes mellitus (n = 60). Normal glucose tolerance, IGT, and diabetes were defined using World Health Organization consulting group criteria. The inclusion criteria were nonsmokers; normal resting 12-lead electrocardiogram; absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases; and subjects not on statins or aspirin. Insulin resistance was calculated using the homeostasis assessment model using the formula: fasting insulin (microIU/mL) x fasting glucose (mmol/L)/22.5. Soluble P-selectin and sCD40L were estimated by enzyme-linked immunosorbent assay. Metabolic syndrome was defined using Adult Treatment Panel III guidelines. Subjects with diabetes and IGT were older (diabetes: 53 +/- 9 years, P < .01; IGT: 51 +/- 10 years, P < .05) compared with the NGT group (48 +/- 10 years). Subjects with diabetes and IGT had higher levels of sP-selectin (diabetes: 162 +/- 79 ng/mL, P < .001; IGT: 102 +/- 37 ng/mL, P < .001) compared with the NGT group (55 +/- 48 ng/mL). Soluble CD40L levels were also higher in those with diabetes and IGT (diabetes: 3.2 +/- 2.0 ng/mL, P < .001; IGT: 2.0 +/- 1.3 ng/mL, P < .001) compared with the NGT group (1.1 +/- 0.9 ng/mL). Subjects with MS had significantly higher levels of sP-selectin (with MS, 118 +/- 76 ng/mL; without MS, 95 +/- 66 ng/mL; P = .028) and sCD40L (with MS, 2.4 +/- 1.8 ng/mL; without MS, 1.9 +/- 1.5 ng/mL; P = .036) compared with subjects without MS. Among subjects with NGT and IGT, the mean levels of sP-selectin (tertile I, 65.0 ng/mL; tertile II, 80.0 ng/mL; tertile III, 91.0 ng/mL) and sCD40L levels (tertile I, 1.2 ng/mL; tertile II, 1.7 ng/mL; tertile III, 1.8 ng/mL) increased with increase in tertiles of homeostasis assessment model-insulin resistance, and the difference reached statistical significance in the last tertile compared with the first tertile (P < .05). This study demonstrates that increased levels of sP-selectin and sCD40L are seen in Asian Indian subjects with IGT, type 2 diabetes mellitus, MS, and insulin resistance.     

Soluble CD40 Ligand Levels in Patients with Hypertension

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.     

Soluble CD40 ligand levels in patients with hypertension

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.     

Plasma apelin levels in subjects with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), one of the most common forms of chronic liver disease, is closely associated with obesity and insulin resistance. Recent studies suggest that apelin, a newly described adipokine, is associated with hyperinsulinemia and inflammation. The aim of the study was to investigate plasma apelin concentrations in biopsy-proven NAFLD patients who had no metabolic confounders and also to search for the association of apelin with adiponectin, body mass index (BMI), and insulin sensitivity. Fifty male patients with NAFLD and 30 healthy male controls were enrolled. Apelin was measured along with BMI, lipids, glucose, insulin, adiponectin, and homeostasis model assessment (HOMA) of insulin resistance indexes. Plasma apelin levels were significantly higher and adiponectin levels were lower in NAFLD patients when compared with the controls (P < .001 and P = .013, respectively). In multivariate analysis adjusted for BMI and HOMA indexes, the differences in apelin and adiponectin disappeared in the 2 groups (P = .3 and P = .1, respectively). In addition, apelin levels were positively correlated with BMI (r = 0.29, P = .05) and HOMA indexes (r = 0.4, P = .008) in subjects with NAFLD. The results of this preliminary study suggest that plasma apelin levels are not altered in nondiabetic and normotensive male subjects with NAFLD.     

Effect of continuous positive airway pressure on soluble CD40 ligand in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis. CD40-CD40 ligand interaction promotes several proinflammatory mediators and plays a pivotal role in the various stages of atherosclerotic diseases. The present study examines whether CD40 ligation contributes to outcomes in patients with OSAS. METHODS: The study population comprised OSAS patients with an apnea hypopnea index (AHI) > or = 30 (n = 35) and control subjects (AHI < 5; n = 16). We measured serum levels of soluble CD40 ligand (sCD40L), tumor necrosis factor (TNF)-alpha, and hypersensitive C-reactive protein (hsCRP) before and after nasal continuous positive airway pressure (nCPAP) therapy for 3 months. RESULTS: Baseline levels of sCD40L were significantly higher in patients with OSAS (6.93 +/- 4.64 ng/mL) [mean +/- SD] than in control subjects (3.43 +/- 2.11 ng/mL, p < 0.01). Baseline levels of sCD40L positively correlated with TNF-alpha but not with hsCRP. The elevation of sCD40L was improved for 1 night after nCPAP therapy (3.83 +/- 2.78 ng/mL, p < 0.001). Even though patients with severe OSAS did not receive any other medication to control atherosclerotic risk factors for 3 months, nCPAP was continued to reduce the levels of sCD40L. CONCLUSION: The present study suggested that sCD40L is a key factor that links OSAS and atherosclerotic progression.     

Enhanced P-selectin expression and increased soluble CD40 Ligand in patients with Type 1 diabetes mellitus and microangiopathy: evidence for platelet hyperactivity and chronic inflammation

Aims/hypothesis Platelet activation, endothelial dysfunction and inflammation may be involved in early stages of diabetic microangiopathy. We therefore investigated patients with Type 1 diabetes mellitus, without (n=19) and with (n=20) microangiopathy, matched for glycaemic control and duration of disease, and matched with healthy control subjects (n=27).Methods Platelet activation was measured as platelet P-selectin expression using whole blood flow cytometry and as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma, serum soluble E-selectin, CD40 ligand (sCD40L) and C-reactive protein (CRP) served as markers for endothelial function and inflammation.Results Thrombin-induced platelet P-selectin expression was enhanced, and soluble P-selectin and sCD40L concentrations were increased in patients with microangiopathy compared with the control subjects (p<0.01 for both) and with patients without microangiopathy (p<0.05 for P-selectin expression and sP-selectin), whereas all three parameters were similar in patients without microangiopathy and in the control subjects. CRP and soluble E-selectin were increased in patients with microangiopathy, compared with the control subjects (p<0.01 and p<0.05), whereas von Willebrand factor did not differ between the groups.Conclusions/interpretation Microangiopathy in Type 1 diabetes is associated with platelet hyperactivity, endothelial dysfunction and low-grade inflammation, indicating an increased risk for cardiovascular disease.Abbreviations sP-selectin Soluble P-selectin - sCD40L soluble CD40 Ligand - CRP C-reactive protein     

阿司匹林对2型糖尿病患者血清可溶性CD40配体水平的影响

目的观察2型糖尿病（T2DM）患者血清可溶性CD40配体（sCD40L）水平的变化，以及阿司匹林（ASP）对其水平的影响。方法T2DM患者55例按是否服用阿司匹林（ASP）分为DM不服用ASP（DMwithoutASP）组24例和DM服用ASP组（DMwithASP）31例，设对照组33例。采用ELISA法测定血清sCD40L水平。结果DM-ASP组较对照组的sCD40L水平升高（2．14±0．74VS1．89±1．07，P〉0．05），DM＋ASP组CD40L较DM组下降（1．19±0．76，P〈0．01），较对照组下降（P〈0．01）。结论DM患者血清sCD40L升高；服用ASP可降低DM患者sCD40L水平。     

CD40配体高表达与不稳定型心绞痛之间的关系

为了探讨不稳定型心绞痛患者外周血单核细胞表达CD40配体及血清可溶性CD40配体变化的临床意义。应用间接免疫荧光流式细胞术和双抗夹心酶联免疫测定法分别对正常对照组 16例、稳定型心绞痛 2 0例、不稳定型心绞痛 2 0例患者血单核细胞表达CD40配体及血清可溶性CD40配体水平进行检测。并观察血清可溶性CD40配体与冠状动脉病变程度的关系。结果发现 ,(1)不稳定型心绞痛组血单核细胞表达CD40配体明显较稳定型心绞痛组和对照组高 (P <0 .0 1) ,稳定型心绞痛组与对照组相比无差异 (P >0 .0 5 )。 (2 )不稳定型心绞痛组血清可溶性CD40配体水平明显较稳定型心绞痛组和对照组高 (P <0 .0 1) ,而稳定型心绞痛组与对照组相比亦有明显差异 (P <0 .0 5 )。 (3)经皮冠状动脉腔内成形术后血清可溶性CD40配体明显高于术前 (P <0 .0 1) ,但血单核细胞表达CD40配体无差异 (P >0 .0 5 )。 (4 )血清可溶性CD40配体水平与冠状动脉病变的复杂狭窄数相关 (r=0 .5 4,P <0 .0 1) ,而与狭窄的程度和范围无关。此结果提示 ,血清可溶性CD40配体升高对冠状动脉斑块的不稳定或破裂起重要作用 ,且可能是冠状动脉病变的活动性标志物。     

Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura

We investigated the levels of various chemokines and soluble CD40L (sCD40L) in ITP patients, in order to determine the influence of CD40-CD40L interaction on the pathogenesis of ITP. We found increases in MCP-1 and RANTES levels in ITP patients compared with those in healthy individuals. Thirty-eight of the 65 ITP patients (58.5%) had elevated levels of sCD40L. We found significant decreases in platelet counts in sCD40L-positive ITP patients. Although the sCD40L level did not differ significantly between the control and nonimmune thrombocytopenia groups, but among ITP patients. sCD40L level was significantly higher in those with untreated ITP than in those with treated ITP. In addition, significant increases in RANTES, MCP-1, sCD14, and sP-selectin levels were observed in sCD40L-positive ITP patients, although sE-selectin levels were not increased in such patients. For other factors examined, however, there were no differences in level between sCD40L-positive and -negative ITP patients. These findings suggests that there are two groups of ITP patients, one with elevated and one with normal of sCD40L. ITP cases in which sCD40L was increased appeared to involve changes in platelet counts and monocyte activation. The pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway.     

No Significant Association Between Vitamin D and Nonalcoholic Fatty Liver Disease in a Chinese Population

Background

Some research evidence from Western populations suggests that lower vitamin D is associated with the prevalence and histologically assessed severity of nonalcoholic fatty liver disease (NAFLD).

Aims

To investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and vitamin D status (deficiency <20 ng/ml; insufficiency 20–30 ng/ml; sufficiency >30 ng/ml) with the prevalence of NAFLD in study population of Chinese.

Methods

Serum 25(OH)D, parathyroid hormone, lipids, liver enzymes, and anthropometric characteristics were measured in 1,248 subjects aged ≥20 years. NAFLD was diagnosed using abdominal ultrasound examination.

Results

The prevalence of NAFLD was 30.3 % in the total study population, 37.9 % in the male subjects, and 20.8 % in the female subjects (P < 0.0001). Subjects with NAFLD had a significantly higher body mass index, higher levels of fasting blood glucose and liver enzymes, and a more atherogenic lipid profile. However, serum 25(OH)D concentrations were not significantly different between subjects with and without NAFLD (22.1 vs. 22.8 ng/ml, respectively; P = 0.21). In addition, a 10 ng/ml higher serum 25(OH)D concentrations [odds ratio (OR) 1.02, 95 % confidence interval (CI) 0.84–1.25, P = 0.82] or vitamin D status (vs. sufficiency: deficiency OR 0.86, 95 % CI 0.54–1.37, P = 0.52; insufficiency OR 0.96, 95 % CI 0.61–1.52, P = 0.87) were not significantly associated with the presence of NAFLD in the multivariate logistic regression analyses.

Conclusions

Serum 25(OH)D concentrations or vitamin D status were not significantly associated with the presence of NAFLD. More studies are needed to elucidate the relationship between vitamin D and the occurrence of NAFLD in Chinese.     

Incremento en las concentraciones de ligando CD40 soluble plaquetario en pacientes con síndrome antifosfolipídico primario

ObjectiveTo determine the concentrations of sCD40L in patients with PAPS, and establish its association with the number of thrombosis.Patients and methodsWe included patients with PAPS and healthy controls of the same age and sex. For analysis, patients with PAPS were divided into 2 groups: 1) patients with 1 thrombosis, and 2) patients with >1 thrombosis. Soluble CD40L concentrations were determined by ELISA method.ResultssCD40L concentrations were significantly higher in patients with PAPS compared with the controls (9.72 ng ± 11.23 ng/ml vs. 4.69 ± 4.04 ng/ml) (P=.04) There was no association between serum levels of sCD40L and the number of thrombosis (1 thrombosis: 9.81 ± 9.87 ng/ml vs 9.63 ± 12.75 ng/ml in ≥ 1 thrombosis (P=.13). In women with pregnancy and abortions, (13 patients) concentrations of sCD40L were higher than in those patients without a history of abortion (26 patients) but without statically significant difference (12.11 ± 16.46 ng/ml vs. 8.80 ± 8.61 ng/ml) (P=.33). There was no correlation between levels of sCD40L and the total number of thrombosis.ConclusionsPatients with PAPS have higher concentrations of sCD40L compared with healthy subjects, although this is not associated with a greater number of thrombosis. Among patients with PAPS, there is a tendency to higher concentrations of sCD40L in women with pregnancy and history of abortion. Since the platelet is the main cellular source of sCD40L, is possible that this pathway plays a pathogenic role in patients with PAPS.     

Plasma levels of asymmetric dimethylarginine in patients with biopsy-proven nonalcoholic fatty liver disease

Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are produced by breakdown of proteins that have been methylated posttranslationally at an arginine residue. Plasma levels of ADMA are elevated in insulin resistance states. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and varying degrees of hepatic dysfunction. Because ADMA is metabolized in the liver, we hypothesized that ADMA levels will be high in patients with NAFLD as a consequence of hepatic dysfunction and insulin resistance. Plasma levels of ADMA, SDMA, total homocysteine, glucose, and insulin were measured in nondiabetic patients with biopsy-proven NAFLD (11 steatosis and 24 nonalcoholic steatohepatitis) and 25 healthy subjects. Plasma ADMA levels were significantly higher (P = .029) in patients with biopsy-proven NAFLD (0.43 ± 0.21 μmol/L) compared with controls (0.34 ± 0.10 μmol/L). However, when adjusted for insulin resistance (homeostasis model assessment), the difference between 2 groups was not evident. Plasma SDMA levels were similar in all 3 groups. Plasma levels of ADMA were positively correlated with plasma total homocysteine levels (P = .003). Plasma levels of SDMA were negatively correlated with estimated glomerular filtration rate (P = .016) and positively correlated with plasma total homocysteine levels (P = .003). The ratio of ADMA/SDMA was positively correlated with body mass index (P = .027). Elevated plasma concentrations of ADMA in biopsy-proven NAFLD were primarily related to insulin resistance. Hepatic dysfunction in NAFLD does not appear to make significant contribution to changes in plasma methylarginine levels.     

Variations in inflammatory markers in acute myocardial infarction: a longitudinal study

Inflammation is now considered a key component of atherosclerosis, from fatty streak formation to plaque rupture, subsequent thrombosis, and progressive mechanical and dynamic obstruction. Rupture of the arterial plaque's fibrous cap exposes tissue factors present in the necrotic core, triggering inflammatory signaling, cell adhesion, and the coagulation cascade that eventually leads to thrombus. Cytokines and adhesion molecules are key components of these events that contribute to the development of an atherosclerotic plaque. The cytokine TNF-alpha and intercellular adhesion molecule-1 (ICAM-1) are indicators of basal inflammation, while the soluble forms of adhesion molecules such as CD40L and P-selectin indicate the extent of platelet activation. This study reports on the follow-up of 17 patients with confirmed acute myocardial infarction (AMI group) undergoing angioplasty and a matched control group of 16 patients without coronary artery disease as verified by coronary angiography. Patients from the AMI group were assessed at the onset of the acute coronary syndrome, within 24 h, before the administration of glycoprotein IIb/IIIa inhibitors and coronary angioplasty, and during the recovery period, two and 40 days after intervention. For both groups, clinical characteristics were documented and serum concentrations of soluble CD40L, P-selectin, ICAM-1, TNF-alpha, and conventional biochemical indicators were analyzed. For AMI patients, these indicators were recorded at study entry and during follow-up. Concentrations of cytokines and adhesion molecules were measured using commercial immunoassay (ELISA) kits. Significant variations in sP-selectin were observed relative to the control group. Immediately after myocardial infarction, sP-selectin levels rose markedly, followed by a sharp decrease two days later. After 40 days of recovery, sP-selectin levels rose again, returning to the initial values. Variations in sCD40L levels were not significant relative to controls. However, sCD40L concentrations tended to fall until the second day after infarction, followed by a rise, and by the 40th day of recovery levels were slightly higher than controls. Unlike sCD40L and sP-selectin, consistently higher levels of TNF-alpha relative to controls were observed, which were only significant after 40 days of recovery. No significant variations were observed for ICAM-1 serum concentrations in the AMI group. The variations observed demonstrate the role of inflammatory markers in AMI progression and highlight the importance of systemic inflammation in disease evolution. The increased concentration of sP-selectin at infarction onset is evidence of thrombosis and platelet activation. Later, during the recovery period when hemodynamic variables are returning to stability in part due to medication, rises in circulating levels of sCD40L and cytokines such as TNF-alpha may reflect the role of these molecules in the recovery of endothelial and myocardial tissues.     

Comparison of diverse platelet activation markers as indicators for left atrial thrombus in atrial fibrillation

Atrial fibrillation (AF) is well known for being a major risk factor of thromboembolic stroke. We could recently demonstrate an association of monocyte–platelet aggregates (MPAs) with the degree of thrombogenicity in patients with AF. This study investigated platelet activation markers, as potential biomarkers for the presence of left atrial (LA) thrombus in patients with AF. One hundred and eight patients with symptomatic AF underwent transesophageal echocardiography (TEE) before scheduled cardioversion or pulmonary vein isolation. In order to determine the content of MPAs by flow-cytometric quantification analyses, blood was drawn on the day of TEE. The soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were obtained by Cytometric Bead Arrays (CBA). D-dimer levels were detected by quantitative immunological determination of fibrin degradation products. Clinical, laboratory, and echocardiographic standard parameters were obtained from all patients, including the determination of the flow in the left atrial appendage (LAA). Patients with detected LA thrombus (n = 28) compared with patients without thrombus (n = 80) showed an increased number of common risk factors, such as age, diabetes, heart failure, and coronary artery disease (CAD). The presence of LA thrombus was associated with significantly increased levels of MPAs (147 ± 12 vs. 304 ± 29 per µl; p < 0.00), sCD40L (106.3 ± 31.0 vs. 33.5 ± 2.1 pg/ml, p = 0.027), and D-dimer (0.13 ± 0.02 vs. 0.69 ± 0.21 mg FEU/l, p = 0.015). In contrast, sP-selectin showed no association with LA thrombus. A multivariate regression analysis showed that MPAs, sCD40L as well as D-dimers were independent indicators for the existence of LA thrombus. MPAs above 170 cells/µl indicated LA thrombus with a high sensitivity of 93% and a specificity of 73% (OR 62, 95% CI. 6.9–557.2, p < 0.001) in patients with AF, whereas the D-dimer lost their quality as independent indicator by using the conventional cut-off of 0.5 mg/l within the regression analysis. MPAs, as well as the D-dimer, correlated significantly negatively with the flow in the LAA measured during TEE. The content of MPAs, sCD40L, and D-dimer, but not sP-selectin showed an increased dependence on LA thrombus in patients with AF. In our study group, MPAs showed the best diagnostic test accuracy of the compared platelet markers. The different results of the examined platelet activation markers could be an indication of diverse mechanisms of LA thrombus in AF. Further studies should evaluate whether determination of MPAs in clinical routine may suffice to indicate the presence of LA thrombus in patients with AF.     

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB–IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 ± 8.2 years), and the rest to the control group (n = 18, aged 63.4 ± 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = −0.72, P = 0.0007), but was absent in the UA group (r = −0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.     

Elevated levels of platelet-monocyte aggregates and related circulating biomarkers in patients with acute coronary syndrome

AimsTo investigate whether patients with acute coronary syndrome (ACS) possessed high levels of platelet–monocyte aggregates (PMAs) and related circulating biomarkers.Methods74 ACS patients, 58 stable angina pectoris (SAP) patients and 46 control patients without coronary artery disease were selected and their PMAs were measured by flow cytometry. Their plasma IL-6, IL-8, MCP-1, soluble CD40L and soluble P-selectin were also measured simultaneously by flow cytometry.ResultsPatients with ACS exhibited higher level of PMAs compared with SAP patients and the control. Furthermore, the levels of IL-6, IL-8, MCP-1, soluble CD40L, soluble P-selectin and CRP were also significantly higher in ACS patients than in SAP patients and the control group. However, there were no significant difference in the levels of IL-8, sCD40L, sP-selectin and CRP between SAP patients and the control group. Correlation analysis showed that high levels of IL-6 and sP-selectin were significantly correlated with PMAs. Logistic analysis further demonstrated that the presence of elevated CRP, IL-6 and PMAs level each confers an increased risk of ACS.ConclusionElevated levels of PMAs and related circulating biomarkers might indicate the unstable coronary syndrome in ACS patients, and the levels of PMAs, CRP and IL-6 could be used for monitoring and guiding the early intervention of ACS patients.     

Serum levels of soluble CD26 and CD30 and their clinical significance in patients with rheumatoid arthritis

The aim of this study was to assess serum levels and clinical significance of soluble CD26 (sCD26) and soluble CD30 (sCD30) in patients with rheumatoid arthritis (RA). Forty-eight patients with RA and 30 healthy controls were enrolled. Serum sCD26 and sCD30 levels were measured using ELISA. Serum sCD26 levels were significantly lower (P?=?0.011), whereas sCD30 levels were higher (P?=?0.008) in patients with RA than controls. Serum levels of sCD30 correlated significantly with clinical and laboratory parameters of disease activity like erythrocyte sedimentation rate, C-reactive protein, disease activity scores-28 and health assessment questionnaire score; however, sCD26 levels did not correlate any of these activity parameters. These results suggest that serum sCD30 levels increased and correlated significantly with disease activity, indicating a novel follow-up parameter in RA. Serum levels of sCD26 may be lessen but not related to disease activity in RA.