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BACKGROUND/PURPOSE: We examined the association between hydroxychloroquine (HCQ) and plasma lipid and glucose levels in rheumatoid arthritis (RA) cohort. METHODS: This is a retrospective cohort analysis of 1261 RA patients comparing fasting lipid profiles and plasma glucose between patients who were and were not taking HCQ. We divided patients into 3 groups based on HCQ exposure during follow-up: those who had never taken HCQ, those who took it intermittently, and those who took it continuously. We used multivariable models and propensity scoring to compensate for the effect of nonrandom treatment assignment. RESULTS: We followed 1261 RA patients for a total of 4605 observations between 1996 and 2014. After adjusting for age, sex, ethnicity, other disease-modifying antirheumatic drugs (DMARDs), lipid-lowering medications, body mass index (BMI), and smoking, patients taking HCQ at baseline had significantly lower total cholesterol (TC) (P ≤ 0.001), low-density lipoprotein (LDL) (P ≤ 0.001), triglycerides (P = 0.013), and lipid profile ratios TC/high-density lipoprotein (HDL) (P ≤ 0.001) and LDL/HDL (P ≤ 0.001), as well as higher HDL (P ≤ 0.001).In longitudinal analyses, after adjusting for confounders, patients who continuously took HCQ showed significantly lower TC, LDL, TC/HDL, and LDL/HDL and higher HDL (P ≤ 0.01). Fasting plasma glucose levels were not significantly associated with HCQ exposure. CONCLUSIONS: Hydroxychloroquine use was associated with lower lipid levels but not with the plasma glucose in this RA cohort. These findings support the need for a randomized trial to establish the role of HCQ in cardiovascular disease prevention in RA patients.
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Artrite Reumatoide , Hidroxicloroquina/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Glicemia/análise , Índice de Massa Corporal , Colesterol/sangue , Feminino , Seguimentos , Humanos , Lipoproteínas LDL/sangue , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Triglicerídeos/sangue , Estados UnidosRESUMO
Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p-values (p < 1 × 10(-4) ). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (ß ± SE = -0.25 ± 0.05, p = 6.23 × 10(-6) ). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p-value < 1 × 10(-4) ). The best association was observed on chromosome 9 with rs59902911 (ß ± SE = 0.86 ± 0.17, p = 1.01 × 10(-6) ), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.
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Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Proteínas Adaptadoras de Sinalização CARD/genética , Articulações/patologia , Proteínas Serina-Treonina Quinases/genética , Artrite Reumatoide/etnologia , Feminino , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Americanos Mexicanos/genética , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos , População Branca/genética , Quinase Induzida por NF-kappaBRESUMO
OBJECTIVE: To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA). METHODS: We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3â years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use. RESULTS: Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571â mm (0.151). After a mean of 2.8â years, the IMT increased by 0.050â mm (0.055), p≤0.001, a progression rate of 0.018â mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10â mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression. CONCLUSIONS: Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT.
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Artrite Reumatoide/imunologia , Aterosclerose/imunologia , Espessura Intima-Media Carotídea , Peptídeos Cíclicos/imunologia , Fator Reumatoide/imunologia , Idoso , Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Sedimentação Sanguínea , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Progressão da Doença , Feminino , Cadeias HLA-DRB1/genética , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Inflamação/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco , Fumar/epidemiologiaRESUMO
BACKGROUND: Death certificates can be used to assess disease prevalence and incidence; however, rheumatoid arthritis (RA) often remains unreported in death certificates. We sought to determine to what extent RA is underreported and what demographic and clinical characteristics could predict mention of RA in the death certificate. METHODS: We recruited 1328 patients with RA from private, public and military rheumatology practices and followed them prospectively for yearly evaluations. A rheumatologist assessed clinical characteristics of RA and comorbidities at each evaluation. Deaths were identified through family members, other physicians, obituaries and public death databases. All were confirmed with state-issued death certificates. Patients with and without RA in death certificate were compared using bivariate and multivariate analyses. RESULTS: By December 2013, 326 deaths had occurred. We received and reviewed death certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the death certificate. Bivariate analysis revealed that younger age, a greater number of deformities, higher Sharp score and lower socioeconomic status were each associated with recording RA. Multivariable analyses revealed that comorbidity [OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with listing RA on the death certificate, while the number of deformities [OR (95 % CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased likelihood of reporting RA. CONCLUSION: In this cohort, RA was not listed in over 80 % of death certificates. Younger patients with fewer comorbidities and more joint deformities were more likely to have RA reported. DISCUSSION: RA is often not included in death certificates. The findings of this study suggest that older patients may have a greater number of comorbidities, thus decreasing the likelihood that RA be included when completing the death certificate.
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Artrite Reumatoide/mortalidade , Idoso , Idoso de 80 Anos ou mais , Atestado de Óbito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Texas/epidemiologiaRESUMO
Introduction: Endometrial stromal sarcoma (ESS) is a rare tumor that remains a diagnostic and therapeutic challenge to physicians worldwide. The metastatic setting implies a poor prognosis, with a 5-year survival rate below 40%. Patients with advanced-stage high-grade ESS (HG-ESS) have limited therapeutic options, often involving various chemotherapy regimens. Case Presentation: This report depicts the case of a 47-year-old female diagnosed with HG-ESS. She underwent several lines of treatment starting with radiotherapy and brachytherapy, followed by multiple lines of treatment including trabectedin over several months. After retreatment with trabectedin and achieving disease stabilization for 10 months, treatment was optimized by trabectedin combined with radiotherapy, leading to stable disease that is still ongoing and lasts for over 17 months. Conclusion: Our case underscores the challenging nature of treating patients with HG-ESS and highlights the safety of long-term retrial with trabectedin, coupled with radiotherapy administration. This approach maintained a durable stable disease response in the metastatic setting.
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OBJECTIVE: The role of atherosclerosis in the acute coronary syndromes (ACS) that occur in patients with rheumatoid arthritis (RA) has not been quantified in detail. We undertook this study to determine the extent to which ACS are associated with carotid atherosclerosis in RA. METHODS: We prospectively ascertained ACS, defined as myocardial infarction, unstable angina, cardiac arrest, or death due to ischemic heart disease, in an RA cohort. We measured carotid atherosclerosis using high-resolution ultrasound. We used Cox proportional hazards models to estimate the association between ACS and atherosclerosis, adjusting for demographic features, cardiovascular (CV) risk factors, and RA manifestations. RESULTS: We performed carotid ultrasound on 636 patients whom we followed up for 3,402 person-years. During this time, 84 patients experienced 121 new or recurrent ACS events, a rate of 3.5 ACS events per 100 patient-years (95% confidence interval [95% CI] 3.0-4.3). Among the 599 patients without a history of ACS, 66 incident ACS events occurred over 3,085 person-years, an incidence of 2.1 ACS events per 100 person-years (95% CI 1.7-2.7). The incidence of new ACS events per 100 patient-years was 1.1 (95% CI 0.6-1.7) among patients without plaque, 2.5 (95% CI 1.7-3.8) among patients with unilateral plaque, and 4.3 (95% CI 2.9-6.3) among patients with bilateral plaque. Covariates associated with incident ACS events independent of atherosclerosis included male sex, diabetes mellitus, and a cumulative glucocorticoid dose of ≥ 20 gm. CONCLUSION: Atherosclerosis is strongly associated with ACS in RA. RA patients with carotid plaque, multiple CV risk factors (particularly diabetes mellitus or hypertension), many swollen joints, and a high cumulative dose of glucocorticoids, as well as RA patients who are men, are at high risk of ACS.
Assuntos
Síndrome Coronariana Aguda/etiologia , Artrite Reumatoide/complicações , Aterosclerose/complicações , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/epidemiologia , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/epidemiologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , UltrassonografiaRESUMO
The authors noticed that content of "Conflicts of Interest" in the original version [...].
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Symptomatic control and tumoral shrinkage is an unmet need in advanced soft-tissue sarcoma (STS) patients beyond first-line. The combination of trabectedin and radiotherapy showed activity in a recently reported clinical trial in this setting. This retrospective series aims to analyze our experience with the same regimen in the real-life setting. We retrospectively reviewed advanced sarcoma patients treated with trabectedin concomitantly with radiotherapy with palliative intent. Growth-modulation index (GMI) was calculated as a surrogate of efficacy. Forty metastatic patients were analyzed. According to RECIST, there was one (2.5%) complete response, 12 (30%) partial responses, 18 (45%) disease stabilizations, and nine (22.5%) progressions. After a median follow-up of 15 months (range 2-38), median progression-free survival (PFS) and overall survival (OS) were 7.5 months (95% CI 2.8-12.2) and 23.5 months (95% CI 1.1-45.8), respectively. Median GMI was 1.42 (range 0.19-23.76), and in 16 (53%) patients, it was >1.33. In patients with GMI >1.33, median OS was significantly longer than in those with GMI 0-1.33 (median OS 52.1 months (95% CI not reached) vs. 8.9 months (95% CI 6.3-11.6), p = 0.028). The combination of trabectedin plus radiotherapy is an active therapeutic option in patients with advanced STS, especially when tumor shrinkage for symptomatic relief is needed.
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BACKGROUND: Myxoid liposarcoma (ML) exhibits a special sensitivity to trabectedin (T) and radiation therapy (RT). Preclinical data suggest a synergistic effect. We aimed to study safety, feasibility and activity of the administration of pre-operative concurrent T and RT in patients affected by localized resectable ML. METHODS: Patients received 3â¯cycles (C) of T in combination with RT (45â¯Gy) in 25 fractions (1.8â¯Gy/fraction). Dose Levels for T were: - 1 (1.1â¯mg/m2), 0 (1.3â¯mg/m2) and 1 (1.5â¯mg/m2). Primary endpoint was safety; antitumor activity was assessed by RECIST and Choi criteria. This study is registered at ClinicalTrials.gov, number NCT02275286. The phase 1 part of the study is complete and phase 2 is ongoing. FINDINGS: From February 2015 to May 2016, 14 patients (M/F 7/7), median age 36â¯years (range 24-70) and median tumor size 12.5â¯cm (range 7-17â¯cm), were enrolled. One dose limiting toxicity (G3 transaminitis) occurred at Level 0 and one (sepsis due to catheter infection) at Level 1. All patients completed RT. Five patients achieved PR (36%), 8 SD (57%), 1 distant PD (7%) by RECIST, while 12 achieved PR (86%), 1 SD (7%) and 1 distant PD (7%) by Choi criteria. Twelve patients underwent surgery. Median viable residual tumor was 5% (0-60). INTERPRETATION: T in combination with RT showed a favorable safety profile and antitumor activity in localized ML. T dose of 1.5â¯mg/m2 is the recommended dose for the phase 2 study, which is ongoing. FUNDING: This study was partially supported by Pharmamar.
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Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS) plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled "A Genetic Association Study of Carotid Intima-Media Thickness (CIMT) and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis" which is being published in Atherosclerosis (Arya et al., 2018) [1].(Arya et al., in press) Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations.
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BACKGROUND AND AIMS: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs). METHODS: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK. RESULTS: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p < 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (ß ± SE = -0.84 ± 0.18, p = 3.80 × 10-6). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, ß ± SE = -0.28 ± 0.06, p = 5.11 × 10-6). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10-6) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10-5) in EAs. CONCLUSIONS: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA.
Assuntos
Artrite Reumatoide/etnologia , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etnologia , Doenças das Artérias Carótidas/genética , Espessura Intima-Media Carotídea , Americanos Mexicanos/genética , Placa Aterosclerótica , Polimorfismo de Nucleotídeo Único , População Branca/genética , Idoso , Artrite Reumatoide/diagnóstico , Carboxiliases/genética , Doenças das Artérias Carótidas/diagnóstico por imagem , Feminino , Perfilação da Expressão Gênica/métodos , Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Proteínas Cotransportadoras de Sódio-Fosfato Tipo I/genética , Texas/epidemiologiaRESUMO
BACKGROUND: Despite high cardiovascular mortality in rheumatoid arthritis (RA), few studies of body mass index (BMI) and obesity as risk factors for death in RA have been published. METHODS: We estimated the effect of BMI on survival in a cohort of 779 patients with RA adjusting for comorbidity, RA disease severity, erythrocyte sedimentation rate (ESR), and other potential confounders. RESULTS: The cohort accrued 123 deaths in 3460 person-years (3.6 deaths per 100 person-years; 95% confidence interval [CI], 3.0-4.2). The BMI was inversely associated with mortality. Patients with BMIs of 30 or higher had the lowest mortality, 1.7 deaths per 100 person-years (95% CI, 1.1-2.5). Mortality was higher in each lower BMI category, reaching its highest rate among patients with BMIs lower than 20 with 15.0 deaths per 100 person-years (95% CI, 9.9-23.0). The survival advantage of high BMI was independent of RA onset age, RA duration, sex, ethnic group, socioeconomic status, smoking status, and use of methotrexate but was lost on adjusting for comorbidity and RA severity. We observed an interaction between BMI and ESR, where the BMI protective influence occurred only if the ESR was low. The BMI x ESR interaction was independent of all covariates, including comorbidity and RA severity. CONCLUSIONS: Body mass has a paradoxical effect on mortality in RA. Patients with high BMI have lower mortality than thinner patients. This effect is mediated in part by comorbidity. The effect of body mass on survival seems to be modified by the level of systemic inflammation.
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Artrite Reumatoide/mortalidade , Sedimentação Sanguínea , Índice de Massa Corporal , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: We have previously proposed a theoretical model for studying physical disability and other outcomes in rheumatoid arthritis (RA). The purpose of this paper is to test a model of impairment and functional limitation in (RA), using empirical data from a sample of RA patients. We based the model on the disablement process framework. METHODS: We posited two distinct types of impairment in RA: 1) Joint inflammation, measured by the tender, painful and swollen joint counts; and 2) Joint deformity, measured by the deformed joint count. We hypothesized direct paths from the two impairments to functional limitation, measured by the shirt-button speed, grip strength and walking velocity. We used structural equation modeling to test the hypothetical relationships, using empirical data from a sample of RA patients recruited from six rheumatology clinics. RESULTS: The RA sample was comprised of 779 RA patients. In the structural equation model, the joint inflammation impairment displayed a strong significant path toward the measured variables of joint pain, tenderness and swelling (standardized regression coefficients 0.758, 0.872 and 0.512, P Assuntos
Artrite Reumatoide/fisiopatologia
, Avaliação da Deficiência
, Modelos Biológicos
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Artrite Reumatoide/complicações
, Artrite Reumatoide/diagnóstico por imagem
, Estudos Transversais
, Edema/diagnóstico
, Edema/etiologia
, Feminino
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Medição da Dor
, Exame Físico
, Radiografia
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OBJECTIVE: To examine the association of socioeconomic status (SES) and delays in disease-modifying antirheumatic drug (DMARD) treatment with clinical measures in rheumatoid arthritis (RA) patients. METHODS: RA patients were recruited from rheumatology practices. We assessed SES based on education, occupation, and income, and divided patients into tertiles. The time from RA symptom onset to DMARD initiation (DMARD lag) was determined by self-report of the 2 dates, and distance to the rheumatologist (Distance) was obtained from Google Maps. We examined disease activity, determined by the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR); joint damage, determined from hand radiographs by Sharp scores; and physical disability, determined by the modified Health Assessment Questionnaire (M-HAQ). We used linear regression models to examine the relationship between clinical measures and SES, Distance, and DMARD lag. RESULTS: We recruited 1,209 RA patients, 1,159 of whom had received DMARD treatment. Mean ± SD DMARD lag was 6.9 ± 9.0 years. On average, patients with lower SES waited 8.5 ± 10.2 years after onset of RA symptoms to begin DMARD treatment, compared to those in the middle and upper SES tertiles who waited 6.1 ± 7.9 years (P = 0.002) and 6.1 ± 8.6 years (P = 0.009), respectively. Each year of delayed treatment was associated with a DAS28-ESR increase of 0.02 (P ≤ 0.001), a Sharp score increase of 1.33 (P ≤ 0.001), and an M-HAQ score increase of 0.01 (P ≤ 0.001). CONCLUSION: Low SES was associated with delay in DMARD initiation, and both were independently associated with worse clinical measures in RA. Strategies to reduce treatment delay in low-SES RA patients are needed.
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Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Pessoas com Deficiência , Acessibilidade aos Serviços de Saúde/economia , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico , Feminino , Humanos , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The objective of this study is to examine the clinical, genetic, and environmental factors associated with interstitial lung disease (ILD) in rheumatoid arthritis (RA). METHOD: We recruited patients with RA from rheumatology practices at the time of a scheduled visit. Each patient participated in a comprehensive assessment that included ascertainment of age, sex, joint tenderness and swelling, subcutaneous nodules, disease severity, use of methotrexate and prednisone, smoking status, rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP),erythrocyte sedimentation rate (ESR), the 28-joint Disease Activity Score (DAS28), and the presence of the HLA-DRB1 shared epitope (SE). As part of a thorough quantification of comorbidity, we identify all comorbid conditions, including ILD. We examined variables associated with ILD using logistic regression. We tested interaction terms between SE and other covariates. RESULTS: We studied 779 RA patients, among whom, ILD was recognized clinically in 69 (8.8 %). Variables significantly associated with ILD in a multivariable analysis included male sex, RA duration, the ESR, the DAS28, anti-CCP, and RF. There was a significant interaction between the HLA-DRB1 SE and smoking, ILD being associated with smoking only in the presence of SE. The association between ILD and anti-CCP, RF, and the ESR displayed a biological gradient, higher titers being more strongly associated with ILD. CONCLUSION: Anti-CCP antibodies and the RF may be pathogenically related to ILD. The association between ILD and smoking is dependent on the HLA-DRB1 SE, which may reflect gene-environment interaction.
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Artrite Reumatoide/complicações , Cadeias HLA-DRB1/genética , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/imunologia , Peptídeos Cíclicos/imunologia , Fumar/imunologia , Adulto , Idoso , Alelos , Artrite Reumatoide/tratamento farmacológico , Sedimentação Sanguínea , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Fator Reumatoide/imunologia , Fatores de Risco , TexasRESUMO
OBJECTIVE: Despite lower socioeconomic status (SES) and higher disease burden, Hispanics in the US paradoxically display equal or lower mortality on average than non-Hispanic whites. Our objective was to determine if the "Hispanic paradox" occurs among patients with rheumatoid arthritis (RA). METHODS: In a cohort of 706 RA patients, we compared differences in RA severity and comorbidity between Hispanic and non-Hispanic white ethnic groups at baseline. Cox proportional hazards models were used to estimate and compare mortality risk between Hispanics and non-Hispanic whites. RESULTS: We studied 706 patients with RA, of whom 434 were Hispanic and 272 were non-Hispanic white. Hispanics had significantly lower SES, greater inflammation, as well as higher tender and swollen joint counts. Patients were observed for 6,639 patient-years, during which time 229 deaths occurred by the censoring date (rate 3.4 per 100 person-years; 95% confidence interval 3.0, 3.9). Age- and sex-adjusted mortality was not significantly different between the 2 ethnic groups (hazard ratio [HR] 0.96). After adjustment for comorbidities, RA severity, and level of acculturation, mortality among Hispanics was lower (HR 0.56, P = 0.004). CONCLUSION: Despite greater severity in most clinical manifestations and lower SES among Hispanics, paradoxically, their mortality was not increased. Further research is needed to understand the mechanisms underlying this survival paradox.
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Artrite Reumatoide/etnologia , Artrite Reumatoide/mortalidade , Hispânico ou Latino/etnologia , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Texas/epidemiologiaRESUMO
OBJECTIVE: To delineate daily and cumulative glucocorticoid dose thresholds associated with increased mortality rates in rheumatoid arthritis (RA). METHODS: We studied RA patients recruited from rheumatology clinics. Annually, we assessed the glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status. We used Cox proportional hazards regression to assess associations between the daily or cumulative glucocorticoid dose and death, adjusting for potential confounders and for the propensity to receive glucocorticoids. We tested strata of the glucocorticoid dose to delineate the threshold associated with death. RESULTS: We studied 779 RA patients with a total of 7,203 person-years of observation, during which 237 of them died, yielding a mortality rate of 3.2 per 100 person-years (95% confidence interval [95% CI] 2.8-3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5-2.1). Exposure to glucocorticoids was associated with a dose-dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05-1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all-cause mortality was 8-15 mg, with an adjusted HR of 1.78 (95% CI 1.22-2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all-cause mortality was 40 gm (HR 1.74 [95% CI 1.25-2.44]). CONCLUSION: Glucocorticoid use in RA is associated with a dose-dependent increase in mortality rates, with a daily threshold dose of 8 mg, at which the number of deaths increased in a dose-dependent manner. These findings may assist clinicians in selecting the appropriate glucocorticoid dosage for RA patients who require these agents.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Dose Máxima Tolerável , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
While genetic and environmental factors and their interactions influence susceptibility to rheumatoid arthritis (RA), causative genetic variants have not been identified. The purpose of the present study was to assess the effects of covariates and genotype x sex interactions on the genome-wide association analysis (GWAA) of RA using Genetic Analysis Workshop 16 Problem 1 data and a logistic regression approach as implemented in PLINK. After accounting for the effects of population stratification, effects of covariates and genotype x sex interactions on the GWAA of RA were assessed by conducting association and interaction analyses. We found significant allelic associations, covariate, and genotype x sex interaction effects on RA. Several top single-nucleotide polymorphisms (SNPs) (~22 SNPs) showed significant associations with strong p-values (p < 1 x 10-4 - p < 1 x 10-24). Only three SNPs on chromosomes 4, 13, and 20 were significant after Bonferroni correction, and none of these three SNPs showed significant genotype x sex interactions. Of the 30 top SNPs with significant (p < 1 x 10-4 - p < 1 x 10-6) interactions, ~23 SNPs showed additive interactions and ~5 SNPs showed only dominance interactions. Those SNPs showing significant associations in the regular logistic regression failed to show significant interactions. In contrast, the SNPs that showed significant interactions failed to show significant associations in models that did not incorporate interactions. It is important to consider interactions of genotype x sex in addition to associations in a GWAA of RA. Furthermore, the association between SNPs and RA susceptibility varies significantly between men and women.
RESUMO
OBJECTIVE: To evaluate the association between peripheral arterial function and cortical bone thickness in rheumatoid arthritis (RA). METHODS: In a cross-sectional study, we measured the combined cortical thickness (CCT) of the second metacarpal bone from hand radiographs, and the ankle-to-arm systolic blood pressure ratio, also known as ankle-brachial index (ABI), in RA patients. We evaluated the association between the 2 using multinomial logistic regression. RESULTS: We obtained CCT and ABI measurements in 588 RA patients. The mean +/- SD CCT was 3.62 +/- 1.16 mm. The proportion of patients with > or =1 ABI value < or =0.9, indicating obstructed lower limb arteries, increased from 18 (9.2%) of 191 patients in the highest CCT tertile to 25 (12.5%) of 200 in the middle CCT tertile to 38 (19.2%) of 198 in the lowest CCT tertile (P for trend 0.005). We noted a similar pattern for ABI values >1.3, indicative of arterial incompressibility (frequencies in high, middle, and low CCT tertiles were 4.7%, 9.5%, and 19.9%, respectively; P for trend < or =0.001). These trends remained significant after multivariable adjustment for potential confounders. After adjustment for the manifestations of RA and cumulative glucocorticoid dose, the association between CCT and arterial obstruction remained significant, but that with arterial incompressibility weakened considerably. CONCLUSION: There is an association between metacarpal cortical bone thinning and obstruction or incompressibility of the peripheral arteries in RA. The association with incompressibility may be mediated by systemic inflammation and/or glucocorticoids, but that with obstruction is independent of a wide array of potential confounders. Clinicians should be alert to the possibility of impaired arterial function RA patients with thinned metacarpal cortical bone.
Assuntos
Artérias/fisiopatologia , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Osso e Ossos/patologia , Idoso , Pressão Sanguínea , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo RegionalRESUMO
Patients with rheumatoid arthritis (RA) are predisposed to atherosclerosis and cardiovascular disease. This is thought to be caused in part, by exposure to chronic systemic inflammation during the course of the disease. We hypothesized that RA disease duration augments the effect of age on atherosclerosis. We measured the carotid artery intima-media thickness (IMT) in 631 consecutive RA patients. We ascertained age, sex and disease duration, established CV risk factors, RA clinical manifestations and markers of inflammation. We used multivariable regression to model IMT, with age as the independent variable. We then added RA duration quartile x age interaction terms to estimate the IMT-age relationship within RA duration strata. We found that the rate at which the IMT increased per unit of age steepened in proportion to the RA duration, from 0.154 mm/10 years among patients with RA for 7 years or less, to 0.295 mm/10 years among patients with RA for 20 years or more (PAssuntos
Artrite Reumatoide/complicações
, Aterosclerose
, Doenças das Artérias Carótidas
, Artéria Carótida Interna/patologia
, Túnica Íntima/patologia
, Túnica Média/patologia
, Adulto
, Fatores Etários
, Idoso
, Aterosclerose/complicações
, Aterosclerose/patologia
, Doenças das Artérias Carótidas/complicações
, Doenças das Artérias Carótidas/patologia
, Artéria Carótida Interna/diagnóstico por imagem
, Feminino
, Humanos
, Estudos Longitudinais
, Masculino
, Pessoa de Meia-Idade
, Fatores de Risco
, Fatores de Tempo
, Túnica Íntima/diagnóstico por imagem
, Túnica Média/diagnóstico por imagem
, Ultrassonografia