Cardiovascular death in rheumatoid arthritis: a population-based study

OBJECTIVE: To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities. METHODS: Using the population-based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death. RESULTS: This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of >or=60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45-2.83), RA vasculitis (HR 2.41, 95% CI 1.00-5.81), and RA lung disease (HR 2.32, 95% CI 1.11-4.84). CONCLUSION: These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.     

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。     

类风湿关节炎相关性间质性肺疾病的临床研究

目的 探讨类风湿关节炎相关性间质性肺疾病(rheumatoid arthritis-associated interstitial lung disease,RA-ILD)的临床特点和相关因素.方法 回顾性分析我院2009年住院的135例RA病例.以患者首次出现RA症状为研究起点,以肺高分辨率CT检查发现ILD为研究终点.研究因素包括:性别、年龄、病程、临床表现(包括关节炎、类风湿结节、发热、口干及眼干、雷诺现象、皮疹等)、生化指标、免疫指标、治疗措施等40个变量.经后退法建立Logestic回归分析模型,计算OR值及95%CI.结果 ①135例RA患者中48例发生ILD,占35.6%.其中40例(83.3%)诊断RA平均(85±75)个月后确诊合并ILD;其中29例(60.4%)在检出ILD时无呼吸系统症状.②单因素分析显示RA-ILD组年龄、病程、咳嗽、呼吸困难、Velcro音、类风湿因子(rheumatoid factor,RF)、C3、γ-球蛋白高于RA无ILD组(P＜0.05或P＜0.01).③经后退法建立Logestic回归分析模型,多因素分析显示咳嗽(OR=4.387,95%CI:1.143～16.831,P＜0.05)、Velcro音(OR=6.727,95%CI:2.220～20.378,P ＜0.01)、RF(OR=3.522,95%CI:1.304～9.512,P ＜0.05)是RA-ILD的危险因素.④多因素分析发现的3个危险因素中,RF预测RA-ILD的敏感性最高(79.2%),咳嗽的阳性预测值最高(73.3%).结论 大多数患者RA的诊断先于ILD.部分RA患者的肺问质病变为亚临床型.咳嗽、Velcro音及RF阳性是RA患者发生肺间质病变的相关因素,当患者出现以上症状、体征或实验室检查异常时应该高度警惕发生肺间质病变可能,及时完善相关检查,给予合理治疗,改善预后.

Abstract：

Objective To analyse the clinical feature and risk factors of rheumatoid arthritisassociated interstitial lung disease (RA-ILD). Methods The data of 135 patients with rheumatoid arthritis (RA) hospitalized in the hospital in 2009 were retrospectively analyzed. The study factors included gender, age, disease duration, clinical manifestations (including arthritis, rheumatoid nodules, fever, dry mouth and dry eyes, Raynaud's phenomenon, skin rash), biochemical and immunological indexes, and treatment measures. The date were analyzed with Logistic regression analysis. Results In 135 RA patients, 48 cases (35.6%) had interstitial lung disease (ILD), in which 40 cases (83.3%) were diagnosed combined ILD (85±75) months after the diagnosis of RA, and 29 cases (60.4%) had no respiratory symptoms in the detection of ILD. Univariate analysis showed that age, duration, incidence of cough, dyspnea and Velcro tone, positive rate of rheumatoid factor (RF), C3 and γ-globulin in RA-ILD group were higher than those in RA without ILD group ( P ＜0.05 or P ＜0.01). Multivariate analysis showed that cough (OR =4.387,95%CI :1.143-16.831, P ＜0.05), Velcro tone (OR =6.727,95% CI :2. 220-20. 378, P ＜0.01),and RF ( OR =3. 522,95% CI :1. 304-9. 512, P ＜0.05) were risk factors of RA-ILD. Multivariate analysis identified that the sensitivity of RF was highest (79.2%), and the positive predictive value of cough was highest (73.3%) in three risk factors. Conclusions RA is diagnosed before ILD in most of patients. The interstitial pulmonary damages of some RA patients are subclinical. Cough,Velcro tone and RF are interrelated factors of interstitial pulmonary damages in RA patients. When patients have these symptoms, signs or abnormal laboratory examination, interstitial lung disease should be highly alerted, the relevant checks should be consummated in time, and rational treatment should be carried out to improve prognosis.     

Association of cardiovascular disease and traditional cardiovascular risk factors with the incidence of dementia among patients with rheumatoid arthritis

ObjectiveTo determine the incidence of dementia in patients with rheumatoid arthritis (RA) 65 years and older, and compare the incidence of dementia in patients with RA with prevalent cardiovascular (CV) disease (CVD), CV risk factors but no prevalent CVD and neither (referent group).MethodsWe analyzed claims data from the Center for Medicare & Medicaid Services (CMS) from 2006–2014. Eligibility criteria included continuous medical and pharmacy coverage for ≥ 12 months (baseline period 2006), > 2 RA diagnoses by a rheumatologist and at least 1 medication for RA. CVD and CV risk factors were identified using codes from the Chronic Condition Data Warehouse. Incident dementia was defined by 1 inpatient or 2 outpatient claims, or one dementia specific medication. Age-adjusted incident rates were calculated within each age strata. Univariate and multivariate Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals.ResultsAmong 56,567 patients with RA, 11,789 (20.1%) incident cases of dementia were included in the main analysis. Age adjusted incident rates were high among all groups and increased with age. After adjustment for age, sex, comorbidities and baseline CV and RA medications, patients with CVD and CV risk factors between 65 and 74 years had an increased risk for incident dementia compared to those without CVD and without CV risk factors (HR 1.18 (95% CI 1.04–1.33) and HR 1.03 (95% CI 1.00–1.11), respectively). We observed a trend towards increased risk in patients between 75 and 84 years with CVD at baseline.ConclusionPatients with RA with both CVD and CV risk factors alone are at an increased risk for dementia compared to those with neither CVD nor CV risk factors; however, this risk is attenuated with increasing age. The impact of RA treatment and CV primary prevention strategies in the prevention of dementia in patients with RA warrants further studies.     

Usefulness of risk scores to estimate the risk of cardiovascular disease in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have an excess burden of cardiovascular (CV) disease (CVD). CV risk scores for the general population may not accurately predict CV risk for patients with RA. A population-based inception cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA from 1988 to 2007 was followed until death, migration, or December 31, 2008. CV risk factors and CVD (myocardial infarction, CV death, angina, stroke, intermittent claudication, and heart failure) were ascertained by medical record review. Ten-year predicted CVD risk was calculated using the general Framingham and the Reynolds risk scores. Standardized incidence ratios were calculated to compare observed and predicted CVD risks. The study included 525 patients with RA aged ≥30 years without previous CVD. The mean follow-up period was 8.4 years, during which 84 patients developed CVD. The observed CVD risk was 2-fold higher than the Framingham risk score predicted in women and 65% higher in men, and the Reynolds risk score revealed similar deficits. Patients aged ≥75 years had observed CVD risk >3 times the Framingham-predicted risk. Patients with positive rheumatoid factor or persistently elevated erythrocyte sedimentation rates also experienced more CVD events than predicted. In conclusion, the Framingham and Reynolds risk scores substantially underestimated CVD risk in patients with RA of both genders, especially in older ages and in patients with positive rheumatoid factor. These data underscore the need for more accurate tools to predict CVD risk in patients with RA.     

Predictors of infection in rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of infections. The exact causes of this increased risk are unknown, but may relate to immunologic disturbances associated with the disease or to the immunosuppressive effects of agents used in its treatment. This study was undertaken to identify predictors of serious infections among patients with RA. Identification of such factors is the necessary first step in reducing the excess risk of infection in RA. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota residents ages >or=18 years, who had been diagnosed with RA between 1955 and 1994, were followed up longitudinally through their complete medical records until January 1, 2000. We examined potential risk factors for the development of all objectively confirmed (by microbiology or radiology) infections and for infections requiring hospitalization. Potential risk factors included RA severity measures (rheumatoid factor positivity, elevated erythrocyte sedimentation rate, extraarticular manifestations of RA, and functional status), comorbidities (diabetes mellitus, alcoholism, and chronic lung disease), and other risk factors for infection (presence of leukopenia, smoking). Predictors were identified using multivariate time-dependent Cox proportional hazards modeling. RESULTS: The 609 RA patients in the cohort had a total followup time of 7,729.7 person-years (mean 12.7 years per patient). A total of 389 patients (64%) had at least 1 infection with objective confirmation, and 290 (48%) had at least 1 infection requiring hospitalization. Increasing age, presence of extraarticular manifestations of RA, leukopenia, and comorbidities (chronic lung disease, alcoholism, organic brain disease, and diabetes mellitus), as well as use of corticosteroids, were strong predictors of infection (P < 0.004) in both univariate and multivariate analyses. Notably, use of disease-modifying antirheumatic drugs was not associated with increased risk of infection in multivariate analyses, after adjustment for demographic characteristics, comorbidities, and disease-related variables. CONCLUSION: We identified a number of strong predictors of infections in a population-based cohort of patients with RA. These results can be used to prospectively identify high-risk patients, who may benefit from closer followup and implementation of preventive strategies.     

Cardiovascular death in rheumatoid arthritis: A population‐based study

Objective

To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities.

Methods

Using the population‐based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages ≥18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death.

Results

This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of ≥60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45–2.83), RA vasculitis (HR 2.41, 95% CI 1.00–5.81), and RA lung disease (HR 2.32, 95% CI 1.11–4.84).

Conclusion

These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.

     

Cardiovascular disease and psychological morbidity among rheumatoid arthritis patients

OBJECTIVES: To examine whether patients with rheumatoid arthritis (RA) with co-morbid cardiovascular disease (CVD) have different psychological morbidity (and psychosocial risk factors for it) compared with RA patients without co-morbid CVD. METHODS: Patients with RA and co-morbid CVD (n = 44; hypertension alone for n = 27) were compared with RA patients without CVD (n = 110). Differences in psychological morbidity (depression and anxiety) and psychosocial risk factors for this (arthritis self-efficacy, acceptance, social support and optimism) were examined while controlling statistically for medical and demographic covariates. RESULTS: Groups did not differ on RA duration, RA activity, marital status or socioeconomic status, but RA patients with co-morbid CVD were older, less likely to be female and less likely to be in employment than those without CVD. RA patients with co-morbid CVD had significantly higher depression and were more likely to score above cut-offs for depression than RA patients without CVD. No differences existed in anxiety, although anxiety appeared to be more common than depression. Low optimism was identified as a possible psychosocial risk factor for depression. CONCLUSIONS: RA patients with co-morbid CVD have higher depression than RA patients without CVD; low optimism is a potentially modifiable risk factor that may mediate this difference. RA patients with co-morbid CVD may benefit from systematic screening for depression and targeted intervention if necessary.     

中老年人群类风湿关节炎合并心血管疾病的相关因素分析

目的 探讨类风湿关节炎患者合并心血管疾病可能的危险因素.方法 回顾性分析唐山市工人医院179例均符合美国风湿学会标准的类风湿关节炎患者的患病情况和心血管疾病危险因素,探讨类风湿关节炎合并心血管疾病的危险因素.结果 单因素分析提示类风湿关节炎合并心血管疾病发生的风险与年龄、类风湿关节炎病程、内膜中膜厚度、DAS28评分、关节外脏器受累数、类风湿因子、血小板计数、C反应蛋白和总胆固醇水平有关(P＜0.05);多因素分析提示类风湿关节炎合并心血管疾病发生的风险与DAS28病情活动性评分(OR=2.403)、关节外脏器受累数(OR=1.197)、类风湿因子(OR =2.510)、血小板计数(OR=1.166)、C反应蛋白(OR=1.700)和总胆固醇(OR=1.351)有关,与其他传统心血管疾病危险因素无关.结论 类风湿关节炎增加了心血管疾病发生的风险,为治疗和预防心血管疾病方面提供部分依据.     

Consensus recommendations on managing the selected comorbidities including cardiovascular disease,osteoporosis, and interstitial lung disease in rheumatoid arthritis

Background:Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities.Methods:The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities.Results:Based on experts’ consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities.Conclusions:These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.     

Chronic lung disease in U.S. Veterans with rheumatoid arthritis and the impact on survival

Assess the impact of chronic lung diseases (CLD) on survival in rheumatoid arthritis (RA). Among participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a prospective cohort of U.S. Veterans with RA, we identified CLD and cardiovascular disease (CVD) using administrative and registry data. Demographics, smoking status, RA characteristics including Disease Activity Score in 28 joints (DAS28), and disease-modifying anti-rheumatic drug (DMARD) use were obtained from registry data, which were linked to the National Death Index to obtain vital status. We evaluated associations of CLD with survival using the multivariable Cox regression models. Among a large (n?=?2053), male-predominant (91%) RA cohort, 554 (27%) had CLD at enrollment. Mortality risk was increased 1.51-fold (95% CI 1.26–1.81) in RA patients with CLD after multivariable adjustment, a risk that was similar to that observed with CVD (HR CLD alone 1.46 [1.03–2.06]; CVD alone 1.62 [1.35–1.94]). Survival was significantly reduced in those with interstitial lung disease (ILD) as well as other forms of CLD. Mortality risk with methotrexate and biologic use was not different in those with CLD compared to those without (p interaction ≥?0.15) using multiple exposure definitions and propensity score adjustment. Mortality risk is significantly increased in RA patients with CLD. This risk is attributable not only to ILD but also to other chronic lung conditions and does not appear to be substantially greater in those receiving methotrexate or biologic therapies. Comorbid lung disease should be targeted as a means of improving long-term outcomes in RA.     

A study of the conventional cardiovascular disease (CVD) risk factors in rheumatoid arthritis (RA) among Indians

ObjectiveTo compare traditional cardiovascular disease (CVD) risk factors and acute phase reactants between subjects with rheumatoid arthritis (RA) and subjects without rheumatoid arthritis (RA).MethodsA pre-designed proforma was completed on each patient with RA and normal controls. It included the demographic details, standard Framingham cardiovascular disease (CVD) risk factors and quantitative C-reactive protein (CRP). The values were statistically compared between the 2 groups.ResultsA total of 56 RA subjects and 31 non-RA subjects (mean age 50 vs. 45 years, women to men ratio 2.1 vs 1.2, both differences insignificant) were included in the study. Among traditional standard Framingham CVD risk factors, moderately significant elevation of low-density lipoprotein-cholesterol (LDL-C) and body mass index (BMI) were observed in subjects with RA as compared to subjects without RA. CRP, a non-traditional CVD risk factor, was significantly elevated in subjects with RA. Presence of hypothyroidism, diabetes, hypertension and smoking showed no significant different difference between RA and the control group.ConclusionAn increase in some of the standard Framingham CVD risk factors and CRP was observed in subjects with RA. Whether intervention for correcting these abnormalities would reduce CVD risk, would be a separate research agenda.     

类风湿关节炎并发心血管损害的临床特点与相关因素

目的 分析类风湿关节炎(rheumatoid arthritis,RA)患者并发心血管损害（CVD）的临床特点及相关因素。方法 回顾性分析RA患者临床资料122例,分为并发CVD的RA (并发CVD组)62例和未并发CVD的RA (单纯RA组)60例为对照组,进行单因素分析和多因素分析,多因素分析采用Logistic回归。结果 并发CVD组中患者发病年龄较小、病程较长,两组差异有统计学意义（P<0.05）,在性别比例、年龄、体质量指数（BMI）差异无统计学意义;并发CVD组中常见损害依次为高血压病、高脂血症和冠心病;心脏超声异常以瓣膜返流(61%)最多见;Logistic回归分析提示28个关节疾病活动度（DAS-28）评分、C反应蛋白（CRP）、总胆固醇（TC）和D二聚体水平升高与并发CVD密切相关。结论 CVD为RA患者常见的关节外表现,且表现多样。DAS-28 评分、CRP、TC和D二聚体水平升高与RA并发CVD密切相关。     

CD13/aminopeptidase N in collagen vascular diseases

To determine the significance of CD13/aminopeptidase N in collagen vascular diseases (CVD), we examined its activity and expression in sera and disease sites of patients with CVD. Significantly higher aminopeptidase activity was detected in bronchoalveolar lavage fluid from patients with interstitial lung diseases due to rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), and Sjögren's syndrome than from control subjects. Increased aminopeptidase activity and increased expression of CD13/aminopeptidase N protein were found in alveolar macrophages from CVD patients with interstitial lung diseases. Significantly higher aminopeptidase activity was detected in pleural effusions from patients with systemic lupus erythematosus (SLE) than in transudate effusions. The mean aminopeptidase activity in synovial fluids from RA patients was significantly higher than from patients with osteoarthritis. The mean value of serum aminopeptidase activity was significantly higher in patients with SLE, RA, SSc, and PM/DM than in normal subjects. This study suggests that the activity of CD13/aminopeptidase N, locally produced in the disease site, is a useful marker for CVD and that CD13/aminopeptidase N may have an important role in the pathogenesis of CVD.     

Poor prognosis in patients with rheumatoid arthritis hospitalized for interstitial lung fibrosis

Fifty-seven patients with rheumatoid arthritis (RA) were treated in hospital for diffuse interstitial lung fibrosis. Although interstitial fibrosis (either on the basis of lung function tests or chest roentgenograms or both) is fairly common among patients with RA, according to this study interstitial fibrosis of sufficient extent or severity to warrant hospitalization was rare: incidence of hospitalization due to the lung disease in RA patients was one case per 3,500 patient-years. Eight patients had a largely reversible lung disease associated with drug treatment (gold, D-penicillamine or nitrofurantoin.) The remaining 49 had interstitial fibrosis of unknown cause. Causes for hospitalization were respiratory and general symptoms in 38, but infiltrations on routine chest roentgenographic examinations alone in eleven patients. Forty-five out of the 49 patients had crackles on auscultation. The most typical findings in lung function tests were restriction and a decreased diffusion capacity. These 49 patients showed a poor prognosis, with a median survival of 3.5 years and a five-year survival rate of 39 percent.     

Bronchoalveolar lavage (BAL) in newly diagnosed patients with collagen vascular diseases

Collagen vascular diseases (CVD) are commonly associated with interstitial lung diseases. Bronchoalveolar lavage (BAL) fluid analysis has important diagnostic value when considered in conjunction with other information. The present study was undertaken in newly diagnosed patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) at presentation to characterise BAL cellular constituents and elucidate the cellular picture in patients with and without pulmonary symptoms and in those with and without radiological (high resolution computed tomography) features of interstitial lung disease. All the patients were non-smokers and had not received any form of treatment for their diseases. The means of percentages of lymphocytes, neutrophils, and macrophages were 23.3%, 6.2%, 70.5% respectively. There was a significant BAL lymphocyte predominance in patients with pulmonary symptoms, and a lymphocyte and neutrophil predominance in those having radiological evidence of interstitial lung disease.     

Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRA

Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case–control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.     

Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthritis patients

Objective

Cardiovascular disease (CVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Disease‐modifying therapies that improve risk factors for CVD, such as dyslipidemia, are desired. This study used an electronic health record to determine if hydroxychloroquine (HCQ) use was associated with an improvement in lipid levels in an inception RA cohort.

Methods

All adult individuals with the initial diagnosis of RA between January 1, 2001, and March 31, 2008, were identified (n = 1,539). Only patients with at least one lipid level post–RA diagnosis were included (n = 706). Information on demographics, medical history, body mass index (BMI), laboratory measures, and medications were collected at office visits. Potential risk and protective factors for dyslipidemia were controlled for in linear mixed‐effects regression models for low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), total cholesterol, triglycerides, LDL/HDL, and total cholesterol/HDL.

Results

Patients were 69% women and 98% white, with a median age of 65 years and a median BMI of 29.8 kg/m². In the adjusted regression models, HCQ use was associated with the following average differences in lipids: LDL decrease of 7.55 mg/dl (P < 0.001), HDL increase of 1.02 mg/dl (P = 0.20), total cholesterol decrease of 7.70 mg/dl (P = 0.002), triglycerides decrease of 10.91 mg/dl (P = 0.06), LDL/HDL decrease of 0.136 (P = 0.008), and total cholesterol/HDL decrease of 0.191 (P = 0.006), which were stable over time.

Conclusion

Use of HCQ in this RA cohort was independently associated with a significant decrease in LDL, total cholesterol, LDL/HDL, and total cholesterol/HDL. Considering these results, its safety profile, and low cost, HCQ remains a valuable initial or adjunct therapy in this patient population at high risk for CVD.     

Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort,IORRA

Abstract

Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case–control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.     

Fibrinopeptide A reactive peptides and procoagulant activity in bronchoalveolar lavage: relationship to rheumatoid interstitial lung disease

Extravascular, primarily, alveolar fibrin deposition is commonly associated with the alveolitis of many interstitial lung diseases including the interstitial lung disease associated with rheumatoid arthritis (RA). We therefore hypothesized that coagulation pathways, which promote fibrin formation, would be activated in the alveolar lining fluids of patients with rheumatoid interstitial lung disease. To test this hypothesis, we studied the bronchoalveolar lavage (BAL) fluids from patients with rheumatoid interstitial lung disease (n = 7) and patients with RA unassociated with interstitial lung disease (n = 10) to characterize and quantitatively compare the BAL procoagulant material and levels of fibrinopeptide A (FPA), which is cleaved from fibrinogen by thrombin. FPA reactive peptide concentrations were significantly greater in rheumatoid interstitial lung disease than RA when normalized per ml of concentrated BAL fluid (p = 0.02), per mg BAL total protein (p = 0.01) or BAL albumin content (p = 0.03) and correlated with BAL antigenic neutrophil elastase concentrations (r = 0.87). Procoagulant activity was present in similar concentration of BAL of patients with RA and rheumatoid interstitial lung disease and was mainly attributable to tissue factor associated with factor VII (or VIIa). Our results demonstrate that tissue factor and factor VII are endogenous in the alveoli of subjects with RA and interstitial lung disease and could interact with distal coagulation substrates which may enter the alveoli in interstitial lung disease to locally promote fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)