The association between functional and morphological assessments of endothelial function in patients with rheumatoid arthritis: a cross-sectional study

Introduction

Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). One of the earliest manifestations of CVD is endothelial dysfunction (ED), which can lead to functional and morphological vascular abnormalities. Several non-invasive assessments of vascular function and morphology can be utilised to assess vascular health, but little is known about the association between each of these assessments in patients with RA, and they tend to be used interchangeably in the literature. The objective of the present study was to examine associations between measures of vascular function and morphology in patients with RA.

Methods

A total of 201 RA patients (155 females, median (25^th to 75^th percentile) age: 67 (59 to 73)) underwent assessments of microvascular endothelium-dependent and endothelium-independent function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside respectively), macrovascular endothelium-dependent and endothelium-independent function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilation respectively), and vascular morphology (pulse wave analysis, carotid intima-media thickness (cIMT), and carotid plaque).

Results

Spearman''s correlations revealed that from the functional parameters, only macrovascular endothelium-independent function was inversely associated with cIMT (-0.294 (P < 0.001)) after applying the Bonferroni correction for multiple comparisons. For carotid plaque, t tests showed that macrovascular endothelium-independent function was lower in patients with plaque than without (15.5 ± 8.3 vs. 23.1 ± 9.1%, P = 0.002, respectively).

Conclusions

With the exception of macrovascular endothelium-independent function, all other measures of vascular function were not associated with vascular morphology. This suggests that different assessments of vascular function and morphology in patients with RA reflect quite distinct mechanisms and phases of the atherosclerotic process and should not be used interchangeably.     

The role of inflammation and cardiovascular disease risk on microvascular and macrovascular endothelial function in patients with rheumatoid arthritis: a cross-sectional and longitudinal study

Introduction

Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular disease (CVD), and it has been postulated that RA disease-related inflammation contributes to endothelial dysfunction. The aim of the present work was to examine predictors (RA-related and CVD risk factors) and anti-tumor necrosis factor-alpha (anti-TNF-α) treatment effects on endothelial function in different vascular beds.

Methods

Microvascular endothelial function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) were analyzed in parallel with disease activity. Individual CVD risk factors and global CVD risk were assessed cross-sectionally in 99 unselected RA patients and longitudinally (baseline, 2 weeks, and 3 months) in 23 RA patients commencing anti-TNF-α therapy.

Results

In this cross-sectional study, regression analyses revealed that markers of RA disease-related inflammation were not associated with microvascular or macrovascular endothelium-dependent function (P > 0.05); global CVD risk inversely correlated with microvascular endothelium-dependent function (P < 0.01) and with macrovascular endothelium-independent function (P < 0.01). In the longitudinal study, only microvascular endothelium-dependent function showed an improvement after 2 weeks of anti-TNF-α treatment when compared with baseline (437% ± 247% versus 319% ± 217%; P = 0.001), but no association was evident between change in endothelial function and change in inflammatory markers.

Conclusions

Classical CVD risk may influence endothelial function more than disease-related markers of inflammation in RA. Classical CVD risk factors and anti-TNF-α medication have different effects on microvascular and macrovascular endothelial function, suggesting that combined CVD-prevention approaches may be necessary. Prospective studies examining whether assessments of vascular function are predictive of long-term CV outcomes in RA are required.     

Lack of association between glucocorticoid use and presence of the metabolic syndrome in patients with rheumatoid arthritis: a cross-sectional study

Lupus nephritis is a major contributor to morbidity and mortality in systemic lupus erythematosus, but little is known about the pathogenic processes that underlie the progressive decay in renal function. A common finding in lupus nephritis is thickening of glomerular basement membranes associated with immune complex deposition. It has been speculated that alterations in the synthesis or degradation of membrane components might contribute to such changes, and thereby to initiation and progression of nephritis through facilitation of immune complex deposition. Matrix metalloproteinases (MMPs) are enzymes that are intimately involved in the turnover of major glomerular basement membrane constituents, including collagen IV and laminins. Alterations in the expression and activity of MMPs have been described in a number of renal diseases, suggesting their relevance to the pathogenesis of various glomerulopathies. The same is true for their natural inhibitors, the tissue inhibitor of metalloproteinase family. Recent data from our group have identified an increase in proteolytic activity within the glomerulus coinciding with the development of proteinuria in the mouse model of systemic lupus erythematosus. (NXB × NZW)F₁ Here we review current understanding of MMP/tissue inhibitor of metalloproteinase function within the kidney, and discuss their possible involvement in the development and progression of lupus nephritis.     

Correlation between endothelial function and carotid atherosclerosis in rheumatoid arthritis patients with long-standing disease

Introduction  

In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident cardiovascular (CV) disease.     

The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study

Introduction  

Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable).     

Shiga toxin glycosphingolipid receptors in microvascular and macrovascular endothelial cells: differential association with membrane lipid raft microdomains

Vascular damage caused by Shiga toxin (Stx)-producing Escherichia coli is largely mediated by Stxs, which in particular, injure microvascular endothelial cells in the kidneys and brain. The majority of Stxs preferentially bind to the glycosphingolipid (GSL) globotriaosylceramide (Gb3Cer) and, to a lesser extent, to globotetraosylceramide (Gb4Cer). As clustering of receptor GSLs in lipid rafts is a functional requirement for Stxs, we analyzed the distribution of Gb3Cer and Gb4Cer to membrane microdomains of human brain microvascular endothelial cells (HBMECs) and macrovascular EA.hy 926 endothelial cells by means of anti-Gb3Cer and anti-Gb4Cer antibodies. TLC immunostaining coupled with infrared matrix-assisted laser desorption/ionization (IR-MALDI) mass spectrometry revealed structural details of various lipoforms of Stx receptors and demonstrated their major distribution in detergent-resistant membranes (DRMs) compared with nonDRM fractions of HBMECs and EA.hy 926 cells. A significant preferential partition of different receptor lipoforms carrying C24:0/C24:1 or C16:0 fatty acid and sphingosine to DRMs was not detected in either cell type. Methyl-β-cyclodextrin (MβCD)-mediated cholesterol depletion resulted in only partial destruction of lipid rafts, accompanied by minor loss of GSLs in HBMECs. In contrast, almost entire disintegration of lipid rafts accompanied by roughly complete loss of GSLs was detected in EA.hy 926 cells after removal of cholesterol, indicating more stable microdomains in HBMECs. Our findings provide first evidence for differently stable microdomains in human endothelial cells from different vascular beds and should serve as the basis for further exploring the functional role of lipid raft-associated Stx receptors in different cell types.     

The association between rheumatoid arthritis and periodontal disease

Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody.     

The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study

Introduction  

Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sleep, psychiatric distress and pain sensitivity in RA.     

The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study

Introduction

Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

We measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA.

Results

Patients with pSS showed increased plasma level of total MPs (mean ± SEM 8.49 ± 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 ± 1.05 n PS Eq, P = 0.004) and SLE (7.3 ± 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 ± 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum β2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P ≤ 0.006).

Conclusions

Plasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.     

Cigarette smoking associates with body weight and muscle mass of patients with rheumatoid arthritis: a cross-sectional,observational study

Introduction  

Rheumatoid arthritis (RA) is associated with altered metabolism leading to muscle wasting. In the general population, cigarette smoking is known to affect body composition by reducing fat and inhibiting muscle synthesis. Even though smoking has been implicated in the pathophysiology and progression of RA, its possible effects on body composition of such patients have not been studied. This cross-sectional study aimed to identify potential associations of smoking with body weight and composition of RA patients.     

Inflammation,endothelial function and atherosclerosis in rheumatoid arthritis

Different techniques have proven to be useful in determining the presence of subclinical cardiovascular disease in patients with rheumatoid arthritis (RA). Doppler imaging with iontophoresis of acetylcholine and flow-mediated, endothelium-dependent vasodilation give information on endothelial dysfunction, an early step in the atherogenesis process. However, there is no good correlation between these two surrogate markers of cardiovascular disease in RA. A single determination of routine laboratory markers of inflammation does not seem to relate to endothelial function in RA. Further research is needed to determine whether microvascular endothelial function is a better predictor of cardiovascular outcome than macrovascular endothelial function in patients with RA.Endothelial dysfunction is an early step in the atherogenesis process of rheumatoid arthritis (RA). In the previous issue of Arthritis Research & Therapy, Sandoo and colleagues [1] reported a cross-sectional study performed on 99 unselected patients with RA to determine the presence of microvascular and macrovascular endothelial function in parallel with disease activity, individual cardiovascular (CV) disease risk factors, and global CV disease. The authors also longitudinally studied 23 patients who had RA and who started on anti-tumor necrosis factor-alpha (anti-TNFα) therapy [1]. In the cross-sectional study, markers of RA-related inflammation were not associated with microvascular or macrovascular endothelium-dependent function, and global CV disease risk inversely correlated with microvascular endothelium dependent function. In the longitudinal study, only microvascular endothelium-dependent function showed an improvement following 2 weeks of anti-TNFα treatment in comparison with baseline, but no association between change in endothelial function and change in inflammatory markers was evident. Considering these results, the authors concluded that classic CV disease risk may influence endothelial function more than disease-related markers of inflammation in RA. They stated that classic CV disease risk factors and anti-TNFα medication have different effects on microvascular and macrovascular endothelial function [1].This interesting study raises a series of points that deserve to be addressed. First, endothelial dysfunction in RA is the result of a complex effect mediated by classic CV risk factors, genetic predisposition, chronic inflammation, pro-oxidative stress, a prothrombotic status, and metabolic abnormalities (such as insulin resistance or dyslipidemia) that to a greater or lesser extent may influence the development of this systemic pathological state [2]. The results reported by Sandoo and colleagues suggest that systemic markers of inflammation - erythrocyte sedimentation rate, C-reactive protein (CRP), and disease activity score using 28 joint counts (DAS28) - and disease duration do not relate to endothelial function in microvascular and macrovascular vascular beds [1]. With respect to this, we feel that a single determination of routine laboratory markers of inflammation may not be useful to provide accurate information on the whole atherosclerotic burden associated with this chronic disease. In this regard, when we conducted a study to assess the association between inflammation measured by CRP values and carotid intima-media thickness (IMT)(another surrogate marker of CV disease) [3], we could not find a correlation between CRP at the time of disease diagnosis or at the time of the ultrasound study and the carotid IMT [4]. Nevertheless, the magnitude and chronicity of the inflammatory response measured by the average CRP values in patients with at least 5 years'' disease duration correlated directly with the presence of atherosclerosis determined by carotid IMT [4]. Therefore, considering the results observed using carotid IMT, we think that an overall assessment of the values of biomarkers of inflammation over a prolonged period of time (that is, the mean value of CRP over at least 5 years'' time), rather than a single determination of these biomarkers, might yield more useful information on the implication of these biomarkers of inflammation in the assessment of endothelial dysfunction of patients with RA.Another important result derived from the study [1] was the poor correlation between different surrogate markers of atherosclerosis. This result is expected given that, in a study we conducted to determine whether a correlation between flow-mediated, endothelium-dependent macrovascular vasodilation and carotid IMT values exists, a correlation between these two surrogate markers of atherosclerosis was observed only in RA patients with a long disease duration (more than 7 years) [5]. Therefore, different techniques may provide information on different stages of the atherosclerotic disease [3]. Unlike laser Doppler imaging with iontophoresis of acetylcholine or flow-mediated, endothelium-dependent vasodilation (which give functional information on endothelial function), carotid ultrasound allows the identification of structural morphological damage that was reported to predict CV events in RA [6,7].An unexpected result from the study by Sandoo and colleagues [1] was the absence of change of flow-mediated, macrovascular, endothelial-dependent function in response to 3 months of anti-TNFα treatment. This finding is in contrast to that of previous reports [8-10]. The authors'' explanation of a better baseline macrovascular endothelial-dependent function in their cohort compared with previous series of RA patients undergoing anti-TNFα therapy may be plausible, as treatment with anti-TNFα may have less impact in RA patients who have an endothelial function similar to that of healthy individuals.Finally, the authors highlight the importance of assessing endothelial function in more than one vascular bed. This conclusion is based on the observations that micro-vascular, but not macrovascular, endothelium-dependent function was associated with global CV disease risk algorithms and that only microvascular endothelium dependent function changed following treatment with anti-TNFα [1]. At this point, replication of these observations by other investigators would be of great help to shed light on this matter.Whether classic CV risk factors are more important than chronic inflammation to establish endothelial dysfunction in RA is, at this point, rather speculative. We feel that, as previously pointed out by Kitas and Gabriel [11], classic CV risk factors are important but not sufficient to explain all of the CV excess risk found in RA. We feel that additional research is needed to determine whether microvascular endothelial function is a better predictor of CV outcome than macrovascular endothelial function in patients with RA.     

Obesity and carotid atherosclerosis in African black and Caucasian women with established rheumatoid arthritis: a cross-sectional study

Introduction

Reported findings on the relationship between adiposity and atherosclerotic cardiovascular disease (ACVD) risk in rheumatoid arthritis (RA) are contradictory and originate in developed populations. Approximately 80% of ACVD now occurs in developing countries. We aimed to ascertain the associations of clinical obesity measures with metabolic cardiovascular risk and atherosclerosis in African women with RA from a developing black and developed Caucasian population.

Methods

The associations of body mass index (BMI) as an indicator of overall adiposity and waist circumference and waist-to-height and waist-to-hip ratios as abdominal obesity indices with metabolic risk factors and high resolution B-mode ultrasound-determined carotid artery atherosclerosis were assessed in multivariate regression models in 203 African women with established RA; 108 were black and 95 Caucasian.

Results

BMI and waist-to-height ratio were higher in African black compared to Caucasian women (29.9 (6.6) versus 25.3 (4.9) kg/m², P = 0.002 and 0.59 (0.09) versus 0.53 (0.08), P = 0.01, respectively). Interactions between population origin and anthropometric measures were not related to metabolic risk factors but were associated with atherosclerosis, independent of confounders and individual terms. In all patients, BMI was related to systolic and diastolic blood pressure but not with serum lipid concentrations whereas abdominal obesity indices were associated with serum lipid concentrations but not with blood pressure values; obesity measures that were associated with plasma glucose concentrations comprised BMI, waist circumference and waist-to-height ratio (P < 0.05 in multiple confounder adjusted analysis). In African Caucasian women, BMI was associated with common carotid artery intima-media thickness (standardized β (95% confidence interval (CI)) = 0.21 (0.03 to 0.38)) and waist-to-hip ratio with plaque (odds ratio (OR) (95% CI) = 1.83 (1.03 to 3.25) for one standard deviation (SD) increase). These relationships were independent of multiple non-metabolic risk factors and explained by metabolic risk factors. In African black women with RA, none of the obesity measures was related to atherosclerosis.

Conclusions

Obesity in women with RA from developing groups of black African descent does not as yet translate into atheroma. In Caucasian women with RA that belong to developed populations, BMI and waist-to-hip ratio should be considered in ACVD risk assessment.     

Monitoring diabetes in patients with and without rheumatoid arthritis: a Medicare study

Introduction

Diabetes mellitus is a key predictor of mortality in rheumatoid arthritis (RA) patients. Both RA and diabetes increase the risk of cardiovascular disease (CVD), yet understanding of how comorbid RA impacts the receipt of guideline-based diabetes care is limited. The purpose of this study was to examine how the presence of RA affected hemoglobin A1C (A1c) and lipid measurement in older adults with diabetes.

Methods

Using a retrospective cohort approach, we identified beneficiaries ≥65 years old with diabetes from a 5% random national sample of 2004 to 2005 Medicare patients (N = 256,331), then examined whether these patients had comorbid RA and whether they received guideline recommended A1c and lipid testing in 2006. Multivariate logistic regression was used to examine the effect of RA on receiving guideline recommended testing, adjusting for baseline sociodemographics, comorbidities and health care utilization.

Results

Two percent of diabetes patients had comorbid RA (N = 5,572). Diabetes patients with comorbid RA were more likely than those without RA to have baseline cardiovascular disease (such as 17% more congestive heart failure), diabetes-related complications including kidney disease (19% higher), lower extremity ulcers (77% higher) and peripheral vascular disease (32% higher). In adjusted models, diabetes patients with RA were less likely to receive recommended A1c testing (odds ratio (OR) 0.84, CI 0.80 to 0.89) than those without RA, but were slightly more likely to receive lipid testing (OR 1.08, CI 1.01 to 1.16).

Conclusions

In older adults with diabetes, the presence of comorbid RA predicted lower rates of A1c testing but slightly improved lipid testing. Future research should examine strategies to improve A1c testing in patients with diabetes and RA, in light of increased CVD and microvascular risks in patients with both conditions.     

The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses

Introduction  

Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA.     

Carotid artery plaque in women with rheumatoid arthritis and low estimated cardiovascular disease risk: a cross-sectional study

IntroductionWe previously reported that most patients with rheumatoid arthritis (RA) and moderate cardiovascular disease (CVD) risk according to the Systematic COronary Evaluation score (SCORE) experience carotid artery plaque. In this study, we aimed to identify patient characteristics that can potentially predict carotid plaque presence in women with RA and a concurrent low CVD risk according to the SCORE.MethodsA cohort of 144 women with an evaluated low risk of CVD (SCORE value of zero) was assembled amongst 550 consecutive patients with RA that underwent CVD risk factor recording and carotid artery ultrasound. Participants had no established CVD, moderate or severe chronic kidney disease, or diabetes. We assessed carotid plaque(s) presence and its associated patient characteristics.ResultsCarotid artery plaque was present in 35 (24.3%) of women with RA. Age, the number of synthetic disease-modifying agents (DMARDs) and total cholesterol concentrations were independently associated with plaque in multivariable stepwise backward regression analysis (odds ratio (95% confidence interval) = 1.15 (1.07 to 1.24), P <0.0001, 1.51 (1.05 to 2.17), P = 0.03 and 1.66 (1.00 to 2.73) P = 0.04), respectively). The area under the curve (AUC) of the receiver operating curve (ROC) for the association with plaque was 0.807 (P <0.0001), 0.679 (P = 0.001) and 0.599 (P = 0.08) for age, total cholesterol concentrations and number of synthetic DMARDs used, respectively. The optimal cutoff value in predicting plaque presence for age was 49.5 years with a sensitivity and specificity of 74% and 75%, respectively, and for total cholesterol concentration, it was 5.4 mmol/l with a sensitivity and specificity of 63% and 70%, respectively. The plaque prevalence was 37.5% in patients (n = 80; 55.6%) with age >49.5 years or/and total cholesterol concentration of >5.4 mmol/l, respectively, compared to only 7.8% in those (n = 64; 44.4%) with age ≤49.5 years or/and total cholesterol concentration of ≤5.4 mmol/l, respectively.ConclusionsApproximately one-third of women with RA who experience a low SCORE value and are aged >49.5 years or/and have a total cholesterol concentration of >5.4 mmol/l, experience high-risk atherosclerosis, which requires intensive CVD risk management.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0576-7) contains supplementary material, which is available to authorized users.     

Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and specifically cardiovascular (CVM) mortality in SLE, and to evaluate systematic coronary risk evaluation (SCORE).

Methods

208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.

Results

During follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking among traditional risk factors, and high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.

Conclusion

With the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.     

Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study

Introduction

Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that plays important roles in immunity and inflammation. Some studies have suggested that polymorphism in the TGFB1 gene is associated with heart disease in the general population. The purpose of the present study was to determine whether common single-nucleotide polymorphisms (SNP) in the TGFB1 gene are associated with ischaemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and to investigate the influence of smoking on any association.

Methods

PCR-based assays were used to determine the genotypes of TGFB1 SNPs including TGFB1-509 C/T (rs1800469, in the promoter region), +868 T/C (rs1800470, in exon 1) and +913 G/C (rs1800471, in exon 1) in 414 subjects with established RA. Genotyping for the +868 SNP was also carried out on a second study population of RA patients (n = 259) with early disease. Serum levels of TGF-beta1 were measured using a commercial ELISA kit. Smoking history and IHD/MI status were obtained on each patient. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses.

Results

The heterozygous genotype of TGFB+868 was associated with an increased risk of IHD (OR 2.14, 95% CI 1.30 - 3.55) and MI (OR 2.42, 95% CI 1.30-4.50), compared to the homozygous genotypes combined. Smoking was an independent risk for IHD and MI, and evidence of interaction between smoking and TGFB+868 was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the TGFB1+868 TC genotype and smoking (OR 2.75, 95% CI 1.59-4.75; and OR 2.58 95% CI 1.33-4.99, respectively), independent of other cardiovascular risk factors. The association of the +868 TC genotype and evidence of +868 TC-smoking interaction with IHD were replicated in a second population of RA patients with early disease. Serum TGF-beta1 levels were not associated with TGFB1 genetic variations, smoking or IHD/MI status.

Conclusions

Interaction between smoking and polymorphism in the TGFB1 gene may influence the risk of IHD and MI in patients with RA.     

Increased frequency of metabolic syndrome among Vietnamese women with early rheumatoid arthritis: a cross-sectional study

Introduction  

Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease, and this occurs early in the disease process. The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in RA; however, little information is available regarding MetS in early RA. We aimed to identify the prevalence of MetS and to determine the potential factors associated with the presence of MetS in Vietnamese women with early RA.     

Associations between cerebral and systemic endothelial function in migraine patients: a post-hoc study

Background  

There is a growing interest in the role of the endothelium in migraine. Recently, our group showed differences in endothelial function between the anterior and posterior cerebral circulation in healthy subjects, reduced vasodilatatory capacity of the posterior cerebral circulation and unimpaired systemic endothelial function in migraine patients without comorbidities. However, the relationship between cerebral and systemic endothelial function and the anterior and posterior cerebral endothelial function in migraine patients is still not clear.