类风湿关节炎相关动脉粥样硬化研究进展

类风湿关节炎心血管事件发生率较正常人增高已日益受到重视 ,研究认为它可能是动脉粥样硬化新的危险因素 ,甚至可能像糖尿病一样 ,成为动脉粥样硬化新的等危症。     

类风湿关节炎与动脉粥样硬化

类风湿关节炎（RA）与动脉粥样硬化关系密切,而传统的心血管危险因素并不能完全解释类风湿关节炎心血管事件增加的原因.类风湿关节炎与动脉粥样硬化有共同的发病机制,其中炎症起着关键作用,如肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6等促炎细胞因子不仅参与类风湿关节炎的发病机制,而且能独立预测类风湿关节炎心血管病（CVD）.一方面,炎症能改变类风湿关节炎患者高密度脂蛋白结构以及低密度脂蛋白和高密度脂蛋白浓度,从而促进动脉粥样硬化和心血管事件.     

中西医治疗类风湿关节炎的研究进展

<正>类风湿关节炎(RA)是一种慢性进行性关节病变为主的自身免疫疾病〔1〕。RA发病率全球为0.5%¹%,我国为0.32%1%,我国为0.32%⁰.36%,有近千万RA患者〔2〕。因诊断与治疗的不当,本病有较高的致残率,严重是危及生命。RA典型的症状为周围性、对称性的多关节炎,病情和病程在临床表现上有个体差异。1现代医学对RA认识、治疗的现状和新进展1.1现代医学对RA病因病理发病机制的研究     

类风湿关节炎蛋白质组学研究进展

蛋白质组学技术通过在蛋白质水平上对机体进行研究以阐述疾病的发生、发展及转归。将蛋白质组学技术应用于类风湿关节炎(RA)的研究,多项研究均证实钙连蛋白A(MRP-8)等蛋白质与RA滑膜局部炎性反应有关,可能参与RA发病。应用表面增强激光解析电离飞行时间质谱技术结合决策树统计方法可建立RA的疾病诊断预测模型。     

生物制剂治疗类风湿关节炎的研究进展

类风湿关节炎(RA)是一类常见致残性自身免疫性疾病,传统的治疗药物主要有非甾体抗炎药、糖皮质激素等,但仍有部分病人病情无法控制,最终导致关节进行性破坏。近年来,多种生物制剂的出现为难治性RA的治疗带来了希望,可以有效控制风湿病活动和改善患者生活质量。该文就生物制剂在RA中的治疗进展作一综述。     

微生物与类风湿关节炎发病的相关性研究进展

<正>类风湿关节炎(rheumatoid arthritis,RA)为自身免疫性疾病,以滑膜炎为病理基础,遗传和环境因素均发挥重要作用。与RA相关的基因被不断发现和验证[1],但并不能完全解释疾病发病,例如有研究发现同卵双胞胎RA的发病一致率仅为15%~30%,部分流行病学家认为个体需具备RA遗传背景并且暴露于某些特定环境下,最终才能导致RA发病[2]。微生物广泛存在于皮肤、阴道、口腔和胃肠道黏     

类风湿关节炎心血管病变的研究进展

类风湿关节炎(RA)是临床中常见的自身免疫性疾病,其病因和发病机制复杂多样,具有较高的致残率和死亡率。除了经常引起关节肿胀、压痛外,心脏受累是RA常见的关节外表现,且与RA患者的预后密切相关。与普通人群相比,RA患者发生心血管疾病(CVD)的风险明显升高,从而会进一步增加患者的死亡风险。除了传统的心血管危险因素,如高血压、高脂血症、吸烟、肥胖、糖尿病、慢性肾脏病等外,一些非传统心血管危险因素如炎症、免疫、抗风湿药物的使用等被发现在RA患者的CVD发病中起重要作用。本文对RA患者合并心脏损害的相关临床表现及危险因素等展开综述,旨在为此类患者的诊断和治疗提供一定理论帮助。     

类风湿关节炎与动脉粥样硬化的关系

类风湿关节炎患者早期死亡风险增高,心血管疾病是其主要的死亡因为.与一般人群相比,类风湿关节炎患者心血管疾病发病风险明显增加.类风湿关节炎伴随的全身炎症反应逐渐被认为在动脉粥样硬化进展中起到非常重要的作用,可导致脂质异常、氧化应激增加、内皮功能障碍、动脉僵硬度增加、胰岛素抵抗加重等促进粥样斑块进展.此外,类风湿关节炎的异...     

Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid arthritis

Increased mortality due to cardiovascular disease in rheumatoid arthritis (RA) patients was reported. Using B-mode ultrasonography we compared intima-media thickness (IMT) and plaque occurrence (indicators of asymptomatic atherosclerosis) in the carotid arteries in 70 pre-menopausal, female RA patients and 40 controls. Correlations with different risk factors were evaluated. The IMT values were higher in RA patients (0.59 mm vs. 0.47 mm, P < 0.0001) and they had more plaques (P = 0.023). In RA patients higher levels of sensitive CRP (P < 0.0001), ICAM (P < 0.0001), VCAM (P < 0.0001), IL-2 (P < 0.001), IL-6 (P = 0.009) and TNF-alfa (P < 0.01) were found. A correlation between IMT and triglycerides (P = 0.018) and a negative correlation between IMT and HDL cholesterol (P = 0.037) were found. With multiple regression analysis the association between IMT and sensitive CRP (P = 0.027) and presence of plaques and apolipoprotein B (P = 0.028) was established. The results indicate that even pre-menopausal, female RA patients had accelerated atherosclerosis. Chronic systemic inflammation may play an important role in atherogenesis.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

Subclinical atherosclerosis among rheumatoid arthritis patients without overt cardiovascular risk factors

Abstract

Objective. To determine the associated factors of subclinical atherosclerosis measured with carotid intima media thickness (CIMT) among rheumatoid arthritis (RA) patients without any overt traditional cardiovascular (CV) risk factors.

Methods. Forty RA patients with matched age and gender healthy controls were recruited. Carotid ultrasound was performed to all subjects. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex reference values. Univariate and multivariate analyses were performed to determine the association between the sociodemographics and disease characteristics of RA with thickened CIMT.

Results. Abnormally thickened CIMT were observed in 11 RA patients (27.5%) and in 4 control subjects (10%), p = 0.04. It was highly prevalent among RA patients with active disease (54.5% vs 17.2%), p = 0.02. Patients with thickened CIMT also tend to have erosive disease, p = 0.06. Seropositive rheumatoid factor (RF) patients also had significantly higher CIMT values as compared with sero-negative patients, p = 0.03. Multivariable logistic regression analysis revealed that active disease was independently associated with thickened CIMT.

Conclusions. RA patients are at risk for subclinical atherosclerosis despite absence of traditional CV risk co morbidities and active disease was the independent factor associated with it.     

Atherosclerosis and inflammation: insights from rheumatoid arthritis

Cardiovascular disease is a major health care problem and the most common cause of death among individuals from developed nations. Our understanding of atherosclerosis has evolved from a passive process resulting in narrowing of the lumen and consequent myocardial ischemia to a dynamic process that involves inflammation. The study of atherosclerosis in patients with chronic inflammation, such as rheumatoid arthritis (RA), will provide insights into the relationship between inflammation and atherosclerosis. We review the relationship between atherosclerosis and inflammation within the context of RA, providing evidence that patients with RA have increased cardiovascular morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis. In addition, traditional and novel cardiovascular risk factors are discussed. Finally, actions that a rheumatologist can take to better control this cardiovascular morbidity are suggested. These can be summarized as follows: (1) careful assessment and treatment of cardiovascular risk, (2) better control of inflammation, and (3) individual risk–benefit evaluation of need for cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and high doses of corticosteroids. Presented as Medicine Grand Rounds at the University of Alberta. This review was supported by grants (HL04012 and HL67964) from the National Institutes of Health.     

Increased prevalence of subclinical atherosclerosis in rheumatoid arthritis patients of Indian descent

BACKGROUND:

Studies have shown that rheumatoid arthritis (RA) patients are two to five times more likely to develop premature cardiovascular disease, thus shortening their life expectancy by five to 10 years. This risk has risen to approximately 12.6% in the urban population and 7.4% in the rural population of India. The Framingham risk score (FRS) identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. An investigation of the patients’ coronary arteries and coronary artery calcification (CAC) – a measure of atherosclerotic plaque – has been found to be a strong predictor of cardiovascular disease.

OBJECTIVE:

To identify important biological markers for easy and non-invasive identification of cardiovascular disease in RA patients, and to investigate whether there is a relationship between the FRS and coronary artery atherosclerosis in RA patients.

METHODS:

The present study included 43 established RA patients and 50 healthy individuals (controls). Traditional and nontraditional risk factors were studied and compared with the control group. Insulin resistance was assessed using the homeostasis model of assessment of insulin resistance (HOMA-IR) and the homeostasis model of assessment of beta cell function. The FRS and the 10-year cardiovascular risk were compared between RA patients and controls. The presence of CAC was determined using electron-beam computed tomography, and the association between the FRS and CAC was examined.

RESULTS:

Significant differences in body mass index, waist circumference, rheumatoid factors (immunoglobulin [Ig]G, IgM and IgA) and inflammatory markers – C-reactive protein and erythrocyte sedimentation rate – were noted. There was significant correlation between HOMA-IR and body mass index, hypertension and C-reactive protein, but no correlation was seen with the homeostasis model of assessment of beta cell function. Significant differences were observed in the nontraditional biomarkers in RA patients, thus supporting their importance. Calcium deposition was observed in only seven RA patients.

CONCLUSIONS:

RA patients with increased C-reactive protein levels and erythrocyte sedimentation rates showed an increase in serum insulin levels and significant differences in HOMA-IR, thus indicating insulin resistance, which could lead to underlying progression of artherosclerosis. Significant differences were observed in the nontraditional risk factors, which could be chosen as biomarkers for endothelial dysfunction. There was a significant correlation between calcium score and the FRS in seven patients, suggestive of an underlying risk of atherosclerosis.     

Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis

Background

Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA).

Methods

Clinical variables, serum FFAs and inflammatory cytokines, homeostasis model assessment for insulin resistance (HOMA-IR), and coronary artery calcium were measured in 166 patients with RA and 92 controls. We compared serum FFAs in RA and controls using Wilcoxon rank sum tests and further tested for multivariable association by adjusting for age, race, sex and BMI. Among patients with RA, we assessed the relationship between serum FFAs and inflammatory cytokines, HOMA-IR, and coronary artery calcium scores using Spearman correlation and multivariable regression analyses.

Results

Serum FFAs did not differ significantly in patients with RA and controls (0.56 mmol/L [0.38–0.75] and 0.56 mmol/L [0.45–0.70] respectively, p = 0.75). Presence of metabolic syndrome was associated with significantly increased serum FFAs in both RA and controls (p = 0.035 and p = 0.025). In multivariable regression analysis that adjusted for age, race, sex and BMI, serum FFAs were associated with HOMA-IR (p = 0.011), CRP (p = 0.01), triglycerides (p = 0.005) and Framingham risk score (p = 0.048) in RA, but not with IL-6 (p = 0.48) or coronary artery calcium score (p = 0.62).

Conclusions

Serum FFAs do not differ significantly in patients with RA and controls. FFAs may contribute to insulin resistance, but are not associated with IL-6 and coronary atherosclerosis in RA.     

Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients

Objectives

Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA.

Methods

Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses.

Results

WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44–271.77), obesity (OR 4.09, 95%CI 1.00–16.68) and WBV (OR 3.98; 95%CI 1.23–12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78–0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05–0.52) are negatively associated with cIMT.

Conclusion

Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis.     

类风湿关节炎患者NGAL、Lp-PLA2及血脂异常对动脉粥样硬化的预测及在转归中的价值

目的探讨类风湿关节炎(RA)患者中性粒细胞明胶酶相关载脂蛋白(NGAL)、脂蛋白相关磷脂酶(Lp-PLA)2及血脂异常对动脉粥样硬化(AS)的预测及转归中的价值分析。方法选择RA患者100例(缓解期48例和活动期52例)、健康人50例作为对照组。采用动脉彩色多普勒超声诊断仪进行AS检查,比较两组AS患病率及总动脉内中膜厚度(IMT)值;计算血浆致动脉粥样硬化指数(AIP);日立7600全自动生化分析仪测定各组总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);采用半自动免疫比浊法检测血清NGAL、Lp-PLA2水平差异;采用Spearman相关分析指标的关系,采用Logistic回归分析RA合并AS的危险因素。结果与对照组相比,RA患者体内TC、TG、LDL-C、NGAL、Lp-PLA2含量显著升高,斑块面积、斑块厚度和IMT数值显著升高,HDL-C含量显著降低(P<0.05)。与RA缓解期患者相比,RA活动期患者体内NGAL、Lp-PLA2含量,斑块面积、斑块厚度和IMT数值显著升高(P<0.05)。RA组中合并AS患者为41例(死亡组15例,非死亡组26例),RA无AS患者59例。与对照组和RA无AS组相比,RA合并AS组TC、TG、LDL-C含量显著升高,斑块面积、斑块厚度和IMT数值显著升高,HDL-C含量显著降低(P<0.05)。与AS非死亡组相比,AS死亡组TC、TG、LDL-C含量显著升高,斑块面积、斑块厚度和IMT数值显著升高,HDL-C含量显著降低(P<0.05)。RA患者体内TC、TG和LDL-C含量、NGAL、Lp-PLA2含量与患者的疾病程度(活动期、缓解期)、是否合并AS、疾病结局(生存、死亡)、斑块面积、斑块厚度和IMT数值呈明显正相关(P<0.05)。RA患者HDL-C含量与患者的疾病程度(活动期、缓解期)、是否合并AS、疾病结局(生存、死亡)、斑块面积、斑块厚度和IMT数值呈明显负相关(P<0.05)。Logistic回归分析结果显示,RA患者体内TC、TG和LDL-C含量、NGAL、Lp-PLA2含量与患者是否合并AS及生存结局密切相关,是其主要的独立危险因素(P<0.05)。结论RA患者血清NGAL、Lp-PLA2水平升高且血脂异常,对RA患者并发AS的病理过程起到预判作用,利于早期发现RA患者出现AS。     

Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis

Objective

Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients.

Methods

Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined.

Results

Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA (P = 0.038).

Conclusion

RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque.     

Unusual CD4+CD28− T lymphocyte subset is implicated in the pathogenesis of early atherosclerosis in patients with rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis which is not fully explained by traditional risk factors. Such excess risk appears to be driven by systemic inflammation.