Evidence for activation of the alternate complement pathway in patients with juvenile rheumatoid arthritis

OBJECTIVE: Complement activation has been shown to occur in patients with juvenile rheumatoid arthritis (JRA). Since the two pathways of complement are activated by different stimuli (the alternate pathway by microbial products and IgA, and the classical pathway by immune complexes), we decided to study the relative contribution of the two pathways of complement activation in patients with JRA. METHODS: In 56 patients with JRA, plasma levels of C3 and C4 were measured by turbidimetric assays, and those of C4d, factor Bb and sC5-9 complex by solid-phase enzyme immunoassays. Levels beyond the mean +/- 2 S.D. of normal were considered abnormal. RESULTS: Plasma C3 and C4 levels were decreased in one patient each. The C4d values were increased in 17 patients, whereas levels of factor Bb were elevated in 42 patients and levels of sC5-9 complex were elevated in 51 patients. The values of factor Bb and sC5-9 had a linear correlation (r = 0.75), but there was no significant correlation between C4d and sC5-9 levels (r = 0.36). CONCLUSION: Complement activation in JRA is initiated predominantly by the alternate pathway and culminates in the formation of terminal membrane attack complex.     

Myocardial inflammation and non-ischaemic heart failure: is there a role for C-reactive protein?

Whereas C-reactive protein (CRP) is acknowledged as a cardiovascular risk marker, there is ongoing discussion about its role as a risk factor. Previous studies focused on the effects of CRP on ischaemic heart failure and atherosclerosis. In this study we investigated distribution of CRP, the Terminal Complement Complex (C5b-9) and macrophages (CD68) in the myocardium of patients suffering from non-ischaemic heart failure and their implication on clinical parameters. Endomyocardial biopsies were taken from 66 patients suffering from dilated cardiomyopathy (DCM). Biopsies were analysed by immunohistochemical and immunofluorescent staining for CRP, C5b-9 and CD68. Viral DNA/RNA for adenovirus, enterovirus, parvovirus B19 and human herpes virus 6 was detected by PCR and Southern blot analysis. Myocardial biopsy findings were correlated with plasma level of hsCRP and NT-proBNP as well as echocardiography, exercise test and NYHA class. In 18 (27%) patients, a positive staining for CRP and in 57 (86%) patients a positive staining for C5b-9 was detected. All patients showed myocardial infiltration with macrophages with an average of 39 cells/mm². CRP, C5b-9 and CD68 co-localised within the myocardium. No correlation was observed for inflammatory proteins and plasma level of hsCRP, NT-proBNP and clinical parameters. CRP is frequently present in the myocardium of patients suffering from DCM and co-localises with C5b-9 and macrophages. CRP may contribute to myocardial damage in DCM via activation of the complement system and chemotaxis of macrophages. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

血浆氧化三甲胺水平对冠心病患者预后的预测作用:剂量-反应Meta分析

目的:探讨冠心病患者的血浆氧化三甲胺(TMAO)水平与主要不良心血管事件(MACE)以及全因死亡风险之间的关系.方法:计算机检索2020年7月前发表并收录在PubMed、EMBASE、中国知网、万方等数据库中评估冠心病患者血浆TMAO水平与MACE(心血管死亡、心肌梗死、脑卒中、血管重建、再入院)及全因死亡风险相关性的...     

Association of high sensitivity C-reactive protein with coronary heart disease prediction, but not with carotid atherosclerosis, in patients with hypertension.

BACKGROUND: Inflammation is believed to predict coronary heart disease (CHD) in healthy subjects and in patients with atherosclerosis. We investigated the association of high sensitivity C-reactive protein (HS-CRP) and other inflammatory markers on cardiovascular outcome, and carotid atherosclerosis in hypertensive patients. METHODS AND RESULTS: We conducted a cross-sectional study of 122 hypertensive patients and compared them with 64 normotensive volunteers. We measured circulating levels of HS-CRP, white blood cells (WBC), albumin, fibrinogen, erythrocyte sedimentation rate, and interleukin-6, and examined the associations with traditional risk factors of CHD, carotid atherosclerosis, and a 10-year risk of CHD, based on the risk prediction algorithm of the Framingham model. The mean of blood pressure (BP) of the hypertensive patients was 163/102 mmHg (normotensives; 118/79 mmHg). The 10-year risk of CHD was higher in the hypertensive patients (9.3 +/- 7.3%) compared with the normotensive volunteers (4.3 +/- 4.2%). Albumin and HS-CRP were significantly higher in the hypertensive patients. Multivariate analysis showed that among markers, only HS-CRP was associated with 10-year risk of CHD (beta=0.13, p=0.03). The BP, body mass index, high-density lipoprotein, WBC count, fibrinogen, and cardiac hypertrophy increased across quartiles of HS-CRP. There was no association between HS-CRP and carotid atherosclerosis in subjects with hypertension and normotension. CONCLUSION: A higher HS-CRP level was associated with a higher risk score of CHD, but not with carotid atherosclerosis, in patients with hypertension.     

The association of serum chemerin level with risk of coronary artery disease in Chinese adults

Chemerin is a newly discovered adipokine which has been found closely associated with obesity, metabolic syndrome (MetS), and inflammatory status. This study will investigate whether serum chemerin levels are associated with coronary artery disease (CAD) independently of other cardiovascular risk factors. This study included a total of 430 subjects (239 with CAD and 191 with non-CAD) who underwent coronary angiography. Anthropometric measurements were performed and chemerin, glucose, lipid profiles, and other biochemical characteristics were measured. The severity of coronary atherosclerosis was estimated by the total number of diseased vessels and Gensini score. Serum chemerin levels were significantly higher in the CAD group than in the non-CAD group (P?=?0.011). The odds ratios (95% CI) of CAD across increasing quartiles of serum chemerin were 1.04 (0.61-1.78), 1.08 (0.63-1.83), and 1.87 (1.07-3.24), (P?=?0.386, 0.508, and 0.012, respectively). Adjusting for age, sex, and other conventional risk factors for CAD did not appreciably alter the results. Serum chemerin levels were significantly increased with an increasing of number of diseased vessels (P?=?0.024). In conditional linear regression models, chemerin levels were positively related to Gensini score even after established cardiovascular risk factors (β?=?0.13, P?=?0.019). Correlation analysis showed serum chemerin levels were significantly associated with TG levels, TC levels, fasting serum insulin, HOMA-IR and MetS (all P?相似文献   

Serum complement C3/C4 ratio, a novel marker for recurrent cardiovascular events

Acute coronary syndrome is an inflammatory disease, during which the complement cascade is activated. We assessed the complement C3 and C4 concentration ratio (C3/C4 ratio) in serum as a potential measurement to predict cardiovascular attacks. Patients with acute coronary syndrome (n=148) were followed after an initial attack for subsequent ischemic cardiovascular events (composite end point of death, myocardial infarction, recurrent unstable angina, or stroke). During the follow-up period (average 555 days), 44 patients met an end point. Blood samples were taken at hospitalization, 1 week, 3 months, and 1 year after hospital admission. Serum complement C3 and C4 concentrations and the C3/C4 ratio were analyzed. Patients with an end point had, throughout the follow-up period, a higher C3/C4 ratio than patients without these end points (repeated measures analysis of variance, p=0.007). When all traditional cardiovascular risk factors and other potential confounding factors were included in a Cox multivariate logistic regression survival analysis, the C3/C4 ratio emerged as the novel risk factor for any new cardiovascular event (odds ratio 1.33, 95% confidence interval 1.08 to 1.63, p=0.007). When the C3/C4 ratio was divided into 4 quartiles, 24% in quartiles 1 and 2 (lowest) and 48% in quartile 4 (highest) had end points during follow-up (odds ratio 3.04, 95% confidence interval 1.27 to 7.29, p=0.01). In conclusion, increased serum C3/C4 ratio is a readily available and novel marker for recurrent cardiovascular events in acute coronary syndrome. The relative increase in serum C3 protein and decrease in C4 protein could explain changes in the C3/C4 ratio.     

The effects of metabolic syndrome versus infectious burden on inflammation, severity of coronary atherosclerosis, and major adverse cardiovascular events

BACKGROUND: The clinical predictors of inflammation in atherosclerosis remain controversial. The objective of this study was to compare the associations of metabolic factors vs. infectious burden (IB) with inflammation, the severity of coronary atherosclerosis, and major adverse cardiovascular events (MACEs). DESIGN, SETTING, AND PATIENTS: Coronary angiography with Gensini score was applied to assess the severity of coronary atherosclerosis in 568 patients with coronary artery disease. Metabolic syndrome (MS) score (0-5) was defined according to the modified criteria of National Cholesterol Education Program Adult Treatment Panel III. IB score (0-7) was defined as the number of seropositivities to several agents. RESULTS: IB score was not associated with plasma C-reactive protein (CRP) concentration, Gensini score, or the risk of MACE. In contrast, MS score significantly correlated with both plasma CRP concentration and Gensini score (P < 0.001 for both). MS score and plasma CRP concentration were also significantly associated with the risk of MACE (hazard ratios 1.51, P < 0.001; and 1.90, P = 0.002, respectively). CONCLUSION: Compared with IB, metabolic abnormalities have a more prominent association with the degree of inflammation, the severity of coronary atherosclerosis, and the risk of MACE in patients with coronary artery disease.     

Plasma homocysteine levels and late outcome after coronary angioplasty

OBJECTIVES: The aim of this study was to evaluate a possible relationship between homocysteine levels on admission and late outcome after successful percutaneous coronary intervention (PCI). BACKGROUND: Increasing evidence suggests that mild to moderate elevation of total plasma homocysteine is a graded and potentially modifiable risk factor for cardiovascular disease and death that appears to be largely independent of other traditional risk factors. METHODS: A total of 549 patients were included after successful PCI of at least one coronary stenosis (> or =50%). End points were cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and a composite of major adverse cardiac events (MACE). The relationship between homocysteine levels and study endpoints was assessed. RESULTS: After a median (+/- SD) follow-up of 58 +/- 20 weeks, 6 patients died of cardiac death, 14 were diagnosed with a new MI, and 71 underwent repeat TLR. A graded relationship between homocysteine levels (quartiles) and freedom from MACE was found (p = 0.01). Homocysteine levels (+/- SD) were associated with cardiac death (14.9 +/- 1.7 micromol/l vs. 9.6 +/- 4.3 micromol/l, p < 0.005), TLR (10.7 +/- 4.4 micromol/l vs. 9.5 +/- 4.3 micromol/l, p < 0.05), and overall MACE (11.0 +/- 4.4 micromol/l vs. 9.4 +/- 4.3 micromol/l, p < 0.005). These findings remained unchanged after adjustment for potential confounders. CONCLUSIONS: Plasma homocysteine is an independent predictor of mortality, nonfatal MI, TLR, and overall adverse late outcome after successful coronary angioplasty.     

Prognostic significance of reticulated platelet levels in diabetic patients with stable coronary artery disease

Abstract

Levels of reticulated platelets (RP) increase during high platelet turnover conditions, and have been shown to correlate with diabetes mellitus (DM) status. Little is known regarding the prognostic significance of levels of RP among patients with stable coronary artery disease (SCAD).

The study consisted of patients with SCAD and DM, who visited our cardiology outpatient clinic between June 2016 and February 2017. RP levels were measured at baseline as immature platelet fraction (IPF)%, using flow cytometry. Outcomes at 2 years consisted of bleeding events and major adverse cardiovascular events (MACE), which included death, myocardial infarction, cerebrovascular accident and urgent revascularization.

The study included 104 patients (mean age - 71.2 ± 9.5 years, 76.9% were male, and 83.7% had hypertension). IPF was significantly higher at baseline among patients who had suffered from a MACE (4.57% vs. 2.53%, p < .001), and lower in patients who had suffered from bleeding events, compared with those who had not (1.57% vs. 3.00%, p = .004). There were higher rates of MACE at higher IPF quartiles (p < .001, AUC-0.770), and higher rates of bleeding at the lowest quartiles (p = .007, AUC-0.781).

In SCAD patients with DM, levels of RP are associated with a higher risk of MACE, and inversely correlated with the risk of bleeding.     

Predictive value of complement activation fragments C3a and sC5b-9 for development of severe disease in patients with acute pancreatitis

BACKGROUND: Complement activation has been shown to occur in patients with acute pancreatitis. However, the diagnostic potential of complement activation products in plasma for predicting severe disease remains unclear to date. METHODS: The daily levels of the complement anaphylatoxin C3a and the soluble terminal complement complex sC5b-9 were determined by ELISA in plasma of patients with mild (n = 16) or severe (n = 14) acute pancreatitis during the first week after onset of symptoms, and in healthy control subjects (n = 14). RESULTS: Both C3a and sC5b-9 were significantly elevated during the first 7 days in plasma of patients with severe acute pancreatitis (C3a: 459.3 +/- 407.5 ng/mL (mean +/- s); sC5b-9: 617.9 +/- 297.7 ng/mL), as compared to patients with mild disease (C3a: 172 +/- 149.5 ng/mL; sC5b-9: 306.7 +/- 167.3 ng/mL) or controls (C3a: 102.3 +/- 19.7 ng/mL; sC5b-9: 40.64 +/- 19.7 ng/mL; P < 0.001, repeated measures ANOVA). The analysis of both parameters in combination during the first week after onset of symptoms revealed a high sensitivity (0.93) and specificity (0.88) as well as high negative and positive predictive values (0.93 and 0.87, respectively) with an odds ratio of 91.0 for the development of pancreatic necrosis (P < 0.0001, Fisher exact test). CONCLUSION: In patients with acute pancreatitis, the plasma levels of complement C3a and sC5b-9 measured daily during the first week after onset of symptoms represent highly specific and sensitive parameters for the prediction of severe acute pancreatitis.     

Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study.

BACKGROUND: Complement factor C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors. This study explored whether plasma levels of C3 and C4 are risk factors for the incidence of cardiovascular disease (CVD). DESIGN: A population-based prospective study of 5850 initially healthy men, 28-61 years old at baseline. METHODS: Plasma levels of C3 and C4 were analysed at the baseline examination. The incidence of coronary events (i.e. fatal or non-fatal myocardial infarction), ischaemic stroke and cardiovascular events (i.e. myocardial infarction, ischaemic stroke or cardiovascular death) was studied over 18 years of follow-up. RESULTS: Adjusted for age, C3 in the fourth quartile (versus the first quartile) was associated with an increased incidence of coronary events [relative risk (RR) 1.54, 95% confidence interval (CI) 1.2-1.9], cardiovascular events (RR 1.56, 95% CI 1.3-1.9), and non-significantly with the incidence of ischaemic stroke (RR 1.31, 95% CI 0.89-1.8). However, after adjustments for smoking, body mass index (BMI), cholesterol, diabetes and systolic blood pressure, these relationships were completely attenuated and non-significant. The relationships were similar for C4 concentrations within the normal range. However, for men with C4 in the top 10% of the distribution (>0.34 g/l), a significantly increased incidence of coronary events was found, which persisted after adjustments for risk factors. CONCLUSION: C3 and C4 show substantial correlations with cardiovascular risk factors, including blood pressure, BMI, and lipids. This relationship accounts for the increased incidence of CVD in men with high C3 levels. However, very high C4 levels may be associated with the incidence of CVD, independently of traditional cardiovascular risk factors.     

High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at greater risk of developing cardiovascular events compared with individuals without RA. Increased risk for cardiovascular disease in these patients is a consequence of atherosclerosis. Case-control studies have shown that increased intima-media thickness (IMT) of the common carotid artery is an indicator of generalized atherosclerosis. Some investigators have suggested that the development of atherosclerosis in RA may be related to the magnitude and chronicity of the systemic inflammation. We examined the relationship between carotid IMT to C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are the most commonly assessed markers of inflammatory response in patients with RA. METHODS: Retrospective review of CRP and ESR values in 47 patients with longterm actively treated (at least 5 years) RA without clinically evident atherosclerosis or its complications, who had been studied for carotid IMT with high resolution B-mode ultrasound. RESULTS: No correlation between ESR and carotid IMT was observed. However, a correlation was found between the maximum CRP values and the carotid IMT (p = 0.009). The distribution of patients in 4 quartiles according to the average CRP values showed significant differences in the carotid IMT (p = 0.03). Those exhibiting the highest mean CRP values (quartile 4) had greater carotid IMT. There was no correlation between CRP at the time of disease diagnosis or at the time of the ultrasound study and the carotid IMT. CONCLUSION: Our study confirms that the magnitude and chronicity of the inflammatory response measured by CRP correlates directly with the presence of atherosclerosis in patients with RA.     

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

Complement activation in patients with systemic lupus erythematosus without nephritis.

OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity.     

Long-term prognostic value of the hemorheological profile in transmural myocardial infarction survivors: 60-month clinical follow-up.

Previous reports have shown several hemorheological and hemostatic abnormalities in acute coronary syndrome survivors. Some of these abnormalities were related to cardiovascular events during a 24-month follow-up. The aim of the present work is to evaluate, in transmural myocardial infarction survivors, the long-term (60 months) prognostic value of the biohemorheological profile determined at hospital discharge. Sixty-four patients (59 men), mean age of 58 +/- 12.0 years, transmural myocardial infarction survivors, were prospectively studied for 60 months (32.0 +/- 17 months, median 33 months). The following cardiovascular events (CVE) were analyzed: death, non-fatal infarction, unstable angina, and stroke. Twenty-nine patients had a CVE (nine died). The following parameters were determined at hospital discharge: plasma viscosity, whole blood viscosity, erythrocyte membrane fluidity, erythrocyte aggregation, protein C, plasminogen inhibitor type I (PAI-1), leukocyte count and elastase. The quartiles were determined for each parameter, grouping patients according to these values. Statistics: Group-t-test, Kaplan-Meier survival curve (with log rank test), and Cox logistic regression. RESULTS: 1) Leukocyte count (p < 0.01), protein C activity (p < 0.05) and erythrocyte membrane fluidity (p < 0.05) were predictors of the CVE curve; 2) The higher the value of the leukocyte count quartile, the higher the risk for a CVE (p < 0.05). Patients with a leukocyte count above the median had 4 times more risk for a CVE; 3) The lower the protein C activity, the higher the risk for a CVE. Those with protein C activity lower than the lowest quartile had double the risk; 4) The higher the membrane polarization value (membrane rigidity), the higher the risk of a CVE; 5) By multivariate analysis the 3 parameters were independent predictors of a CVE. CONCLUSION: In the present group of transmural myocardial infarction survivors a close relationship was established between hemorheologic, hemostatic and inflammatory factors and the cardiovascular events curve during long-term follow-up.     

Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans

Objectives  Visfatin is a new cytokine that act as an insulin analogue on the insulin receptor and may link obesity and insulin resistance. It was recently shown that visfatin plays a role in plaque destabilization. However, the role of visfatin in atherosclerosis remains to be elucidated. We sought to assess whether plasma visfatin level is independently associated with inflammation, atherosclerosis and acute coronary syndromes (ACS).
Design and patients  Two hundred and fifty-three patients undergoing coronary angiography were divided into three subgroups: chronic coronary artery disease (CAD) ( n  = 102), ACS ( n  = 100) and control patients ( n  = 51). The plasma samples were thawed and analysed for circulating visfatin, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP). The association of visfatin with risk factors, inflammation, atherosclerosis, and ACS was determined.
Results  Plasma visfatin levels were significantly higher in chronic CAD and ACS compared with control patients. Multiple regression analysis demonstrated that plasma visfatin levels correlated with inflammatory factors and were associated with chronic CAD (odds ratio [OR][95% confidence interval], for second, third and fourth quartiles were 1·74 [0·96–2·69], 1·54 [0·85–2·28] and 1·84 [0·98–2·87], respectively) and ACS (ORs for second, third and fourth quartiles were 2·56 [1·57–3·34], 4·61 [1·94–10·96] and 6·52 [2·34–18·12], respectively) following adjustment for established risk factors and other inflammatory factors.
Conclusions  Plasma visfatin levels are significantly associated with CAD, particularly ACS, independent of well-known CAD risk factors.     

Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis

To elucidate the associations between Lp(a) levels and coronary and aortic atherosclerosis, we performed aortic MRI in 143 patients undergoing coronary angiography. Severity of aortic atherosclerosis was represented as plaque scores. Of the 143 patients, 104 had coronary artery disease (CAD). Thoracic and abdominal aortic plaques were found in 89 and 131 patients. Lp(a) levels increased stepwise with the number of stenotic coronary vessels: 15.7 (CAD(-)), 21.2 (1-vessel), 21.4 (2-vessel), and 22.9 mg/dl (3-vessel) (P<0.05). For aortic atherosclerosis, 143 patients were divided into quartiles by plaque scores. Lp(a) did not differ among quartiles of thoracic plaques: 17.1, 19.0, 23.5, and 21.2 mg/dl (P=NS), whereas Lp(a) increased stepwise with quartiles of abdominal plaques: 17.1, 19.2, 19.1, and 24.0 mg/dl (P<0.05). Lp(a) was an independent factor for CAD and abdominal aortic plaques, but not thoracic plaques. Thus, Lp(a) levels were associated with aortic atherosclerosis, especially in abdominal aorta, as well as coronary atherosclerosis.     

Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. OBJECTIVE: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors. METHODS: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age /=4 determinations multiplied by the disease duration (r = -0.40, p<0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol (beta = -0.40, p<0.05), average CRP levels multiplied by the disease duration (beta = -0.44, p<0.05), and brachial artery diameter (beta = -0.28, p<0.05). CONCLUSIONS: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.     

Complement activation in atherosclerosis: effect of angiography and surgery

Complement activation in the plasma of patients with severe atherosclerosis (arterial occlusive or aneurysmatic disease) was investigated in this study. The effects of angiography and reconstructive arterial surgery (RAS) were also assessed. Atherosclerosis was not found to be associated with systemic complement activation. Angiography resulted in high levels of C3 breakdown products. Surgery caused a significant degree of systemic complement activation in both patients with atherosclerosis and controls. Post-operative levels of C3 breakdown products were significantly higher in atheromatic patients than in controls, most likely due to the insertion of dacron arterial prostheses in the first group.     

Complement activation induced by purified Neisseria meningitidis lipopolysaccharide (LPS), outer membrane vesicles, whole bacteria, and an LPS-free mutant.

Complement activation is closely associated with plasma endotoxin levels in patients with meningococcal infections. This study assessed complement activation induced by purified Neisseria meningitidis lipopolysaccharide (Nm-LPS), native outer membrane vesicles (nOMVs), LPS-depleted outer membrane vesicles (dOMVs), wild-type meningococci, and an LPS-free mutant (lpxA(-)) from the same strain (44/76) in whole blood anticoagulated with the recombinant hirudin analogue. Complement activation products (C1rs-C1 inhibitor complexes, C4d, C3bBbP, and terminal SC5b-9 complex) were measured by double-antibody EIAs. Nm-LPS was a weak complement activator. Complement activation increased with preparations containing nOMVs, dOMVs, and wild-type bacteria at constant LPS concentrations. With the same protein concentration, complement activation induced by nOMVs, dOMVs, and the LPS-free mutant was equal. The massive complement activation observed in patients with fulminant meningococcal septicemia is, presumably, an indirect effect of the massive endotoxemia. Outer membrane proteins may be more potent complement activators than meningococcal LPSs.