RESUMO
OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.
Assuntos
Clínicos Gerais , Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Reumatologistas , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: RA associates with an increased rate of sudden cardiac death (SCD). A prolonged QTc interval has been associated with arrhythmogenic and SCD in patients with long QT syndrome. Despite the previously reported contemporary association of CRP with SCD, thus far no studies have examined the association of QTc with mortality in RA, a condition characterized by high inflammatory burden. The aim of this study was to examine the role of electrocardiography (QT corrected interval) in predicting all-cause mortality in patients with RA who have an increased rate of SCD and a high inflammatory burden. METHODS: Three hundred and fifty-seven RA patients with detailed baseline clinical characterization and 12-lead ECGs were followed up for a mean of 73.0 (S.D. 18.3) months. Linear and Cox regression analyses were used to identify variables that associate with QTc and examine its association with all-cause mortality. RESULTS: The patients' mean age was 60.6 (S.D. 12.0) years, 267 (74.8%) were females and 54 (15.1%) died during the follow-up period. Age (ß = 0.231, P < 0.001), gender (ß = 0.137, P = 0.008) and CRP (ß = 0.144, P = 0.006) associated independently with QTc in RA patients. The crude hazard ratio (HR) for total mortality per 50-ms increase in QTc was 2.17 (95% CI 1.21, 3.90). This association remained significant [HR = 2.18 (95% CI 1.09, 4.35)] after adjustment for identified confounders (cardiovascular and RA specific), but was lost [HR = 1.73 (95% CI 0.83, 3.62)] when CRP was included in the model. CONCLUSION: A 50-ms increase in QTc interval associates with a doubling of the hazard for all-cause mortality in patients with RA. The observed contemporary association of QTc with CRP levels indicates a potentially hazardous interplay between inflammation and arrhythmogenesis. Future studies are needed to confirm the above findings and explore underlying mechanisms.
Assuntos
Artrite Reumatoide/mortalidade , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Inflamação/complicações , Síndrome do QT Longo/complicações , Artrite Reumatoide/complicações , Causas de Morte/tendências , Morte Súbita Cardíaca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Inflamação/mortalidade , Síndrome do QT Longo/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Reino Unido/epidemiologiaRESUMO
Disturbance of fibrinolysis is common in rheumatoid arthritis (RA), and it may be associated with the increased cardiovascular risk observed in this population. We aimed to assess coagulation derangement and investigate whether abnormalities are influenced by demographic, inflammatory or metabolic factors in patients with RA. Levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), fibrinogen, prothrombin fragment 1 + 2 (PF1 + 2), thrombomodulin (TM), protein C and Von Willebrand factor (vWF) were compared between 141 RA patients and 50 healthy hospital controls. Within RA, coagulation factors were assessed alongside several demographic, inflammation and metabolic indicators. RA patients had higher levels of coagulation factors than controls. After correction for age and sex, having RA predicted increased tPA (B = 0.15, P < 0.001), PAI-1 (B = 0.21, P < 0.001), fibrinogen (B = 0.86, P < 0.001), PF1 + 2 (B = 0.20, P < 0.001), and TM (B = 0.01, P = 0.03) levels. CRP correlated positively with tPA (P < 0.05), fibrinogen (P < 0.001), TM (P < 0.05), PF1 + 2 (P < 0.001) and vWF (P < 0.001). Metabolic factors linked with coagulation factors were hypertriglyceridaemia (tPA, P < 0.05; PAI-1, P < 0.05; protein C, P < 0.05) and insulin resistance (tPA, P < 0.01; PAI-1, P < 0.01; vWF, P < 0.05). Imbalance of coagulation and fibrinolytic mechanisms is common in RA and associates with age, inflammation, and metabolic factors. Further studies may determine whether these abnormalities are the consequence of acute inflammation or markers of vascular dysfunction.
Assuntos
Artrite Reumatoide/sangue , Transtornos da Coagulação Sanguínea/sangue , Fibrinólise , Hemostasia , Idoso , Artrite Reumatoide/fisiopatologia , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/complicações , Estudos Transversais , Feminino , Fibrinogênio/metabolismo , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteína C/metabolismo , Protrombina , Análise de Regressão , Fatores de Risco , Trombomodulina/sangue , Ativador de Plasminogênio Tecidual/sangue , Fator de von Willebrand/metabolismoRESUMO
Rheumatoid arthritis (RA) is associated with increased mortality due to cardiovascular disease (CVD). Abnormalities in coagulation have been linked with CVD in general and RA population. The aim of our study is to determine whether particular single nucleotide polymorphisms thought to be involved in the regulation of coagulation are over-represented in patients with RA compared to controls. We compared the frequency of atherothrombotic polymorphisms (Factor V Leiden, fibrinogen G455A, prothrombin G20210A and plasminogen activator inhibitor 4G5G) in 322 RA patients [231 females, mean age 61.5 ± 12, median disease duration 10 years (IQR = 14)] with 441 local controls. No significant differences were observed in genotype or allele frequencies either between RA and controls or between the disease subgroups studied. Whereas these polymorphisms may be of importance at the level of individual patients, they are unlikely to be clinically important on a population basis.
Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Fator V/genética , Feminino , Fibrinogênio/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Inativadores de Plasminogênio/genética , Protrombina/genéticaRESUMO
OBJECTIVE: Rheumatoid arthritis (RA), a condition with a strong genetic etiology, is associated with excess cardiovascular disease (CVD). Dyslipidemia in RA may be driven by inflammation and genetic factors. Apolipoprotein E (ApoE) is important for the regulation of lipid levels and CVD risk and immune function in the general population. We compared the frequency of 2 ApoE single-nucleotide polymorphisms (SNP) in patients with RA and controls, and studied the relationship of ApoE genotypes with lipids and inflammation in RA. METHODS: A total of 387 patients with well-characterized RA and 420 non-RA controls were studied. Two ApoE SNP, rs7412 (ApoE2) and rs429358 (ApoE4), were identified. RESULTS: Genotypic (p = 0.908) and allelic (p = 0.894) frequencies did not differ between RA and controls. Within RA, the E2 allele was associated with the lowest and E4 allele with the highest levels of total cholesterol (p = 0.007), low-density lipoproteins (p = 0.004), and apolipoprotein B (p = 0.009). The E4 allele was also associated with lower C-reactive protein (p = 0.007), erythrocyte sedimentation rate (p = 0.001), and Disease Activity Score (p = 0.015) compared to the E3 allele. E2 or E4 alleles were not associated with CVD in RA, although a trend was observed (p = 0.074). CONCLUSION: The frequency of ApoE polymorphisms did not differ between patients with RA and controls. ApoE genotypes are strongly linked to inflammation and lipid levels in RA, raising interest in the prognostic implications of ApoE genotypes.
Assuntos
Apolipoproteína E2/genética , Apolipoproteína E4/sangue , Apolipoproteína E4/genética , Artrite Reumatoide/genética , Dislipidemias/genética , Inflamação/genética , Polimorfismo Genético , Adulto , Idoso , Apolipoproteína E2/sangue , Apolipoproteínas B/sangue , Artrite Reumatoide/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Colesterol/sangue , Dislipidemias/sangue , Feminino , Frequência do Gene , Humanos , Inflamação/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Rheumatoid arthritis (RA), a systemic inflammatory disease with complex genetic aetiology, associates with excess cardiovascular morbidity and mortality. Dyslipidaemia, a major cardiovascular risk factor has been reported to predate the onset of RA, thus suggesting a potential genetic link between the two conditions. The authors assessed whether RA susceptibility genes associate with the presence of dyslipidaemia in RA patients. METHODS: 400 well-characterised RA patients were included in this cross-sectional study. Fasting lipid profile (total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, apolipoproteins (ApoA and ApoB) and lipoprotein (a)) and four RA susceptibility genes (PTPN22, TRAF1/C5, STAT4 and human leucocyte antigen shared epitope (HLA-SE)) were assessed and associations were sought in both univariate and multivariate analyses. RESULTS: Following adjustment for age, sex and erythrocyte sedimentation rate, the G allele of TRAF1/C5 associated with lower total cholesterol (p=0.010), LDL (p=0.022) and ApoB (p=0.014); one or more copies of the shared epitope associated with lower ApoA (p=0.035) and higher ApoB:ApoA ratio (p=0.047); while STAT4 TT homozygotes had higher lipoprotein (a) (p=0.004). CONCLUSIONS: RA susceptibility genes (TRAF1/C5, STAT4 and HLA-DRB1-SE) may be involved in the regulation of lipid metabolism in RA patients, thus contributing to cardiovascular disease (CVD) risk and adverse outcome. If these findings are replicated, such genotyping could be used to identify and target for prevention those RA patients most at risk of CVD. It will also be interesting to study the association of these genes with lipid levels in the general population and identify mechanisms to explain the link.
Assuntos
Artrite Reumatoide/genética , Dislipidemias/genética , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Fator de Transcrição STAT4/genética , Fator 1 Associado a Receptor de TNF/genéticaRESUMO
Patients with rheumatoid arthritis (RA) are at high risk of cardiovascular events. Platelet biomarkers are involved in inflammation, atherosclerosis and thrombosis. Cardiovascular and RA-associated factors can alter the structure and function of platelets, starting from megakaryocytopoiesis. Reactive megakaryocytopoiesis increases circulating platelets count and triggers hyperactivity. Hyperactive platelets target synovial membranes with subsequent local rheumatoid inflammation. Hyperactive platelets interact with other cells, and target the vascular wall. Accumulating evidence suggests that disease modifying anti-rheumatic drugs (DMARD) decrease platelet activity.
Assuntos
Artrite Reumatoide/metabolismo , Plaquetas/metabolismo , Doenças Cardiovasculares/metabolismo , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Antígenos CD40/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Micropartículas Derivadas de Células/metabolismo , Humanos , Selectina-P/sangue , Trombose/metabolismoRESUMO
Rheumatoid arthritis (RA) associates with excess cardiovascular (CV) morbidity and mortality. New screening tools are needed to better identify patients at increased CV risk. Microalbuminuria (MA) has been shown to associate with inflammation and future cardiovascular disease (CVD). In the present study, we assessed the prevalence of MA in a secondary care cohort of RA patients, aimed to identify factors associated with its presence and addressed its relationship to CVD and the metabolic syndrome (MetS). A total of 342 RA patients were studied. MA was defined as an albumin-creatinine ratio ≥22 (males) or ≥31 (females) milligrams per gram creatinine. The independence of the associations of MA was evaluated using binary logistic regression analysis. Prevalence of MA was 11.9%. Subjects with MA had increased prevalence of hypertension (HT), insulin resistance and type 2 diabetes. In binary logistic regression, only HT (OR = 5.22, 95%CI: 1.51-18.07, p = 0.009) was significantly associated with MA. There was no association between prevalent CVD and MA, but patients with MA had twofold increased odds of having the MetS. MA is relatively common in RA patients and is independently associated with the presence of HT. Given the association of MA with MetS, future prospective studies are needed to establish the use of MA as a screening tool for RA patients at increased CVD risk.
Assuntos
Albuminúria/complicações , Artrite Reumatoide/complicações , Compostos de Ouro/uso terapêutico , Hipertensão/complicações , Penicilamina/uso terapêutico , Idoso , Albuminúria/epidemiologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Inflamação/complicações , Inflamação/epidemiologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Rheumatoid arthritis (RA) associates with excess cardiovascular risk and there is a need to assess that risk. However, individual lipid levels may be influenced by disease activity and drug use, whereas lipid ratios may be more robust. A cross-sectional cohort of 400 consecutive patients was used to establish factors that influenced individual lipid levels and lipid ratios in RA, using multiple regression models. A further longitudinal cohort of 550 patients with RA was used to confirm these findings, using generalized estimating equations. Cross-sectionally, higher C-reactive protein (CRP) levels correlated with lower levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol ([HDL-C] P ≤ .015), whereas lipid ratios did not correlate with CRP. The findings were broadly replicated in the longitudinal data. In summary, the effects of inflammation on individual lipid levels may underestimate lipid-associated cardiovascular disease (CVD) risk in RA, thus lipid ratios may be more appropriate for CVD risk stratification in RA.
Assuntos
Artrite Reumatoide/sangue , Dislipidemias/sangue , Lipídeos/sangue , Idoso , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/metabolismo , Estudos de Coortes , Estudos Transversais , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
The inflammatory pathogenesis of atherosclerosis is now well-established, owing to in vitro and in vivo studies and the application of high sensitivity assays for C-reactive protein (CRP) in the general population and specific groups at risk for cardiovascular disease (CVD). In view of the complexity of inflammation-induced atherosclerosis, the rationale for comparative studies of atherogenesis in rheumatic diseases with diverse inflammatory pathogenesis seems obvious; they are human in vivo models to study inflammatory mechanisms involved in atherosclerosis and the impact of treatment. Factors implicated in atherogenesis in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), familial Mediterranean fever (FMF) and Behçet's disease (BD) are discussed in this review. Evidence suggests that enhanced atherosclerosis causes premature cardiovascular events in the autoimmune disease, SLE, and the "high-grade" inflammatory rheumatic disease, RA. Preliminary data suggest that enhanced atherogenesis may accompany FMF in the absence of sufficient suppression of inflammation by colchicine. In the setting of BD, the role of atherosclerosis in the premature manifestation of coronary pathology has not been confirmed; coronary vasculitis and aneurysms appear to constitute the basis of myocardial infarction (MI) in BD. A variety of established and novel risk factors are believed to influence enhanced atherogenesis in rheumatic diseases. Antiphospholipid antibodies are thought to be intimately involved in atherogenesis in SLE and to a lesser extend in RA. CRP may play a more universal role in all rheumatic diseases. The application of high resolution ultrasound of peripheral arteries and other non-invasive techniques may allow targeted use of statins, ACE inhibitors, antiplatelet agents and other cardioprotective drugs in patients with rheumatic diseases, but this needs to be evaluated specifically in prospective studies.
Assuntos
Aterosclerose/prevenção & controle , Aterosclerose/fisiopatologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/fisiopatologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Biomarcadores/sangue , Progressão da Doença , Humanos , Mediadores da Inflamação/sangue , Projetos de Pesquisa , Doenças Reumáticas/complicações , Doenças Reumáticas/metabolismo , Fatores de RiscoRESUMO
OBJECTIVES: Statins are widely prescribed in patients with rheumatoid arthritis (RA). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced myopathy. Several factors increase the risk of developing statin-induced myopathy, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (SLCO1B1). We aimed to identify the frequency of risk factors for statin-induced myopathy and establish whether the rs4149056 genotype is more prevalent in RA. METHODS: A total of 396 RA patients and 438 non-RA controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. RESULTS: Almost 80% of RA patients had one or more risk factor (range 1-5) for the development of statin-induced myopathy. Of the 74 RA patients treated with statins, 90% had one or more (range 1-4) risk factors. No differences in genotype or allelic frequencies were observed between RA patients and controls. CONCLUSIONS: RA patients harbour multiple risk factors for statin-induced myopathy. However, the frequency of the rs4149056 genotypes does not differ according to the presence of RA. Despite this, no cases of statin-induced myopathy were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among RA patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record myopathy risk factors in these patients.
Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/induzido quimicamente , Transportadores de Ânions Orgânicos/genética , Polimorfismo de Nucleotídeo Único , Artrite Reumatoide/induzido quimicamente , DNA/genética , Frequência do Gene , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Transportador 1 de Ânion Orgânico Específico do Fígado , Proteínas de Membrana , Doenças Musculares/complicações , Doenças Musculares/genética , Prevalência , Risco , Fatores de RiscoRESUMO
Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders associated with enhanced cardiovascular morbidity and mortality. Established high prevalence of classical cardiovascular risk factors may only partly explain cardiovascular phenomenon in this disease. Emerging risk factors, markers of inflammation and prothrombotic state such as platelet size are believed to reflect activity of RA. We aimed to study mean platelet volume (MPV) in a cohort of patients with RA and to clarify possible effects of classical cardiovascular and RA-associated risk factors on MPV. Demographic, clinical and a wide range of laboratory parameters, including MPV and platelet count, were obtained for 400 RA patients. Platelet size and count were also assessed in 360 non-RA controls from the local population. We found significantly increased MPV in RA patients compared with controls (P=0.001). The difference retained significant after adjustment for age and sex. High values of MPV (>or=10.7 femtoliter [fL]) were more frequent in RA patients than in controls (21% vs. 9.2%; P<0.0001). In RA patients, blood pressure greater than 140/90 mmHg was associated with high levels of MPV (Odds Ratio [OR] 2.2, 95% Confidence Interval [CI] 1.3-3.7; P=0.003). It is possible that MPV as a surrogate marker of platelet function reflects enhanced vascular risk. To further explore the role of MPV as a marker for cardiovascular risk in RA, prospective studies are warranted.
Assuntos
Artrite Reumatoide/sangue , Plaquetas/patologia , Tamanho Celular , Hipertensão/epidemiologia , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/sangue , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Contagem de Plaquetas , Fatores de RiscoRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is characterised by increased cardiovascular morbidity and mortality. Even though hypertension (HT) is highly prevalent in RA, the extent of target organ damage (TOD) caused by it remains unknown. Inflammation and sympathetic overdrive may also associate with TOD. We investigated the prevalence and associations of TOD in RA. METHODS: In this cross-sectional, observational study, 251 RA patients with no overt cardiovascular or renal disease had extensive clinical and laboratory evaluations, including a 12-lead electrocardiogram and urine albumin:creatinine ratio. Pulse pressure (PP) was used as a proxy of arterial stiffness and heart rate (HR) of autonomic activity. TOD was defined as described in the European guidelines for the management of arterial hypertension. Binary logistic regression analysis was used to evaluate the independence of the variables that associated with the presence of TOD. RESULTS: TOD prevalence was 23.5% (59/251). Of the 59 patients with TOD, 45.8% had suboptimally controlled HT, whereas 32.3% had undiagnosed HT. In univariable analysis, TOD was significantly associated with higher age (64.2+/-11.7 years vs. 58.0+/-12.4 years, p=0.001), HT prevalence (89.8% vs. 60.4%, p<0.001), systolic blood pressure (SBP) (150.3+/-18.8mmHg vs. 139.7+/-20.7mmHg, p=0.001), PP (70.6+/-16.6mmHg vs. 60.3+/-17.3mmHg, p<0.001), HR (77.1+/-15.4bpm vs. 72.2+/-12.2bpm, p<0.001), serum uric acid (320.6+/-88.8mumol/l vs. 285.0+/-74.9mumol/l, p=0.03) and type 2 diabetes mellitus prevalence (13.6% vs. 4.7%, p=0.019). Binary logistic regression analysis revealed that only hypertension indices and HR associated independently with TOD. CONCLUSIONS: TOD is highly prevalent in patients with RA and associates independently with hypertension, arterial stiffness and heart rate. Further prospective studies are needed to confirm these findings and examine the role of beta-blockers in this particular population.
Assuntos
Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Pressão Sanguínea , Frequência Cardíaca , Índice de Gravidade de Doença , Idoso , Estudos Transversais , Feminino , Humanos , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cardiovascular disease (CVD) is partially attributed to traditional cardiovascular risk factors, which can be identified and managed based on risk stratification algorithms (Framingham Risk Score, National Cholesterol Education Program, Systematic Cardiovascular Risk Evaluation and Reynolds Risk Score). We aimed to (a) identify the proportion of at risk patients with rheumatoid arthritis (RA) requiring statin therapy identified by conventional risk calculators, and (b) assess whether patients at risk were receiving statins. METHODS: Patients at high CVD risk (excluding patients with established CVD or diabetes) were identified from a cohort of 400 well characterised patients with RA, by applying risk calculators with or without a x1.5 multiplier in specific patient subgroups. Actual statin use versus numbers eligible for statins was also calculated. RESULTS: The percentage of patients identified as being at risk ranged significantly depending on the method, from 1.6% (for 20% threshold global CVD risk) to 15.5% (for CVD and cerebrovascular morbidity and mortality) to 21.8% (for 10% global CVD risk) and 25.9% (for 5% CVD mortality), with the majority of them (58.1% to 94.8%) not receiving statins. The application of a 1.5 multiplier identified 17% to 78% more at risk patients. CONCLUSIONS: Depending on the risk stratification method, 2% to 26% of patients with RA without CVD have sufficiently high risk to require statin therapy, yet most of them remain untreated. To address this issue, we would recommend annual systematic screening using the nationally applicable risk calculator, combined with regular audit of whether treatment targets have been achieved.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Distribuição por Idade , Fatores Etários , Idoso , Algoritmos , Doenças Cardiovasculares/etiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/etiologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de PacientesRESUMO
G-protein beta 3 subunit (GNB3) C825T (rs5443) single nucleotide polymorphism (SNP) has been implicated as a risk factor for essential hypertension in the general population. The effects of this SNP may be more prominent in subjects with endothelial dysfunction (ED). Rheumatoid arthritis (RA) is associated with ED and has a high prevalence of hypertension. Thus far, this SNP has not been studied in RA patients. We genotyped 383 RA patients and 432 controls. GNB3 C825T was identified using real-time polymerase chain reaction (PCR) and melting curve analysis. There were no differences in the frequencies of the GNB3 C825T genotype and alleles between RA and controls. Within RA patients, prevalence of hypertension did not differ across genotypes. The TT versus CC+CT contrast yielded an adjusted odds ratio (OR) of 0.92 (95% CI: 0.49 to 1.76, p = 0.813), the contrast of TT+CT versus CC an adjusted OR of 2.17 (95% CI: 0.885 to 5.30, p = 0.091), whereas that of the T allele versus C allele an adjusted OR of 1.11 (95% CI: 0.76 to 1.61, p = 0.604). Systolic and diastolic blood pressure levels were not significantly different across the three genotypic groups. No significant interaction was observed between GNB3 825C/T polymorphism and serum endothelin levels. Data from the present study suggest that the T825 variant of the G protein beta 3 subunit gene is unlikely to constitute major susceptibility loci for essential hypertension in Caucasian RA patients. Further larger studies are required to confirm our findings and assess the interaction of rs5443 with environmental factors.
Assuntos
Artrite Reumatoide/complicações , Pressão Sanguínea/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética , Hipertensão/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Artrite Reumatoide/fisiopatologia , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Endotelina-1/metabolismo , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , População Branca/genéticaRESUMO
INTRODUCTION: Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment. METHODS: Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA. RESULTS: Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results. CONCLUSIONS: UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.
Assuntos
Artrite Reumatoide/complicações , Nefropatias/complicações , Ácido Úrico/sangue , Artrite Reumatoide/sangue , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/sangue , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
INTRODUCTION: The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX. METHODS: MetS prevalence was assessed cross-sectionally in 400 RA patients, using five MetS definitions (National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of the MetS. Further analysis established the nature of the association between MTX and the MetS. RESULTS: MetS prevalence rates varied from 12.1% to 45.3% in RA according to the definition used. Older age and higher HAQ scores associated with the presence of the MetS. MTX use, but not other disease modifying anti-rheumatic drugs (DMARDs) or glucocorticoids, associated with significantly reduced chance of having the MetS in RA (OR = 0.517, CI 0.33-0.81, P = 0.004). CONCLUSIONS: The prevalence of the MetS in RA varies according to the definition used. MTX therapy, unlike other DMARDs or glucocorticoids, independently associates with a reduced propensity to MetS, suggesting a drug-specific mechanism, and makes MTX a good first-line DMARD in RA patients at high risk of developing the MetS, particularly those aged over 60 years.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Síndrome Metabólica/epidemiologia , Metotrexato/uso terapêutico , Adulto , Fatores Etários , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , PrevalênciaRESUMO
The galectin-2 (LGALS2) 3279 C/T single nucleotide polymorphism (SNP) has recently been associated with myocardial infarction (MI). Although hypertension, a very prevalent entity in rheumatoid arthritis (RA), is one of the greatest risk factors for MI, the possible association of LGALS2 3279 C/T and hypertension has not been investigated. We genotyped 386 RA patients, 272 hypertensives and 114 normotensives. Diastolic blood pressure (DBP) was significantly lower in TT compared to CC homozygotes (-4.11 mmHg, p = 0.044) even when adjusted for multiple confounders (-4.28 mmHg, p = 033). Further studies are required to replicate the potential association of LGALS2 3279 C/T with DBP, and examine whether this SNP could be used as a marker of increased risk for future cardiovascular events in RA populations.
Assuntos
Artrite Reumatoide/genética , Galectina 2/genética , Hipertensão/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Idoso , Artrite Reumatoide/complicações , Pressão Sanguínea , Feminino , Genótipo , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Cardiovascular morbidity and mortality are increased in rheumatoid arthritis (RA). Interleukin-6 (IL-6) is high in RA and, together with smoking and obesity, an important contributor to the development of cardiovascular disease (CVD). The present study examined the potential association of IL-6-174 G/C polymorphism, together with obesity and smoking, with the presence of CVD in RA patients. METHODS AND RESULTS: DNA samples were collected from 383 RA patients (who also had extensive clinical and laboratory evaluations). IL-6-174 G/C was identified using real time PCR and melting curve analysis. Serum IL-6 levels were measured in a subgroup of 135 RA patients to examine the functionality of the polymorphism. Carriers of the IL6-174C-allele demonstrated increased prevalence of CVD (26.2% vs. 17.0%, p=0.041). There was a significant association with CVD, even after adjustment for traditional CVD risk factors (OR=1.92, 95%CI: 1.03 to 3.58, p=0.041). IL-6 levels were significantly increased in C-allele carriers [14.02 (3.21-38.81) vs. 4.48 (2.25-16.5), p=0.028]. No significant interactions were observed between adiposity and IL6-174G/C genotypes. There was only a trend for an interaction between ever smoking and IL6 C-allele carriers on CVD. CONCLUSION: The IL-6-174C-allele may associate with CVD in RA patients and possibly exerts its effect via increased inflammation. This finding, if confirmed in future studies, may be used as a part of a genetic screening tool for RA patients at high CVD risk.
Assuntos
Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Interleucina-6/genética , Obesidade/complicações , Polimorfismo Genético , Fumar/efeitos adversos , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Razão de Chances , Prevalência , Medição de Risco , Fatores de Risco , Fumar/epidemiologiaRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality, attributed to both traditional and novel cardiovascular risk factors. The metabolic syndrome, a cluster of classical cardiovascular risk factors, including hypertension, obesity, glucose intolerance, and dyslipidaemia, is highly prevalent in RA. Reports suggest that long-term glucocorticoid (GC) use may exacerbate individual cardiovascular risk factors, but there have been no studies in RA to assess whether it associates with the metabolic syndrome. We examined whether GC exposure associates with the presence of metabolic syndrome in patients with RA. METHODS: RA patients (n = 398) with detailed clinical and laboratory assessments were categorised into three groups according to GC exposure: no/limited (<3 months) exposure (NE), low-dose (<7.5 mg/day) long-term exposure (LE), and medium-dose (greater than or equal to 7.5 mg to 30 mg/day) long-term exposure (ME). The metabolic syndrome was defined using the National Cholesterol Education Programme III guidelines. The association of GC exposure with the metabolic syndrome was evaluated using binary logistic regression. RESULTS: The metabolic syndrome was present in 40.1% of this population and its prevalence did not differ significantly between the GC exposure groups (NE 37.9% versus LE 40.7% versus ME 50%, P = 0.241). Binary logistic regression did not demonstrate any increased odds for the metabolic syndrome when comparing ME with LE (odds ratio = 1.64, 95% confidence interval 0.92 to 2.92, P = 0.094) and remained non significant after adjusting for multiple potential confounders. CONCLUSIONS: Long-term GC exposure does not appear to associate with a higher prevalence of the metabolic syndrome in patients with RA. The components of the metabolic syndrome may already be extensively modified by other processes in RA (including chronic inflammation and treatments other than GCs), leaving little scope for additive effects of GCs.