RESUMO
OBJECTIVES: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. METHODS: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. RESULTS: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. CONCLUSION: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.
Assuntos
Artrite Reumatoide/diagnóstico , Doenças Cardiovasculares/etiologia , Abandono do Hábito de Fumar , Fumar/efeitos adversos , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento de Redução do Risco , Índice de Gravidade de Doença , Fumar/sangue , Fumar/fisiopatologiaRESUMO
OBJECTIVES: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. METHODS: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. RESULTS: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). CONCLUSIONS: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Adulto , Idoso , Colesterol/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
OBJECTIVES: Atherosclerotic cardiovascular disease risk is increased in rheumatoid arthritis (RA). Wave reflection occurs at arterial branching points, which are particularly prone to atherosclerosis. We explored the relationship of wave reflection with atherosclerosis in RA. METHODS: One hundred and sixty three RA patients (110 white, 31 Asian, 17 black and 5 of mixed ancestry) without cardiovascular disease participated. Arterial stiffness, wave reflection, pressure pulsatility, plaque in the extracranial carotid artery tree and the mean of the left and right common carotid arteries intima-thickness were determined. Associations were identified in multivariable regression models. RESULTS: One SD increase in reflected wave pressure (OR (95% CI) = 2.54 (1.41-4.44), p=0.001), reflection magnitude (OR (95% CI) = 1.84 (1.17-2.89), p=0.008), central pulse pressure (OR (95% CI) = 1.89 (1.12-3.22), p=0.02) and peripheral pulse pressure (OR (95% CI) = 2.09 (1.23-3.57), p=0.007) were associated with plaque. The association of wave reflection with plaque was independent of arterial stiffness and pressure pulsatility, and was present in both hypertensive and normotensive RA patients. In receiver operator characteristic curve analysis, the optimal cutoff value for reflected wave pressure in predicting plaque presence was 25 mmHg with a sensitivity, specificity, positive predictive value and negative predictive value of 45.2%, 89.3%, 78.6% and 66.2%, respectively; a reflected wave pressure of >25 mmHg was associated with plaque in univariate and adjusted analysis (p<0.0001 for both). Arterial function was not independently related to carotid intima-media thickness. CONCLUSIONS: Consideration and therapeutic targeting of wave reflection may improve cardiovascular disease prevention in RA.
Assuntos
Artrite Reumatoide/epidemiologia , Doenças Assintomáticas , Aterosclerose/diagnóstico , Placa Aterosclerótica/diagnóstico , Idoso , Aterosclerose/epidemiologia , Aterosclerose/fisiopatologia , Pressão Sanguínea/fisiologia , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/fisiopatologia , Fluxo Pulsátil/fisiologia , Análise de Onda de Pulso , Análise de Regressão , Rigidez Vascular/fisiologiaRESUMO
Omentin is an adipokine that reportedly protects against cardiometabolic risk. We investigated the relationships between omentin concentrations and subclinical cardiovascular disease in rheumatoid arthritis (RA). Omentin concentrations were measured in 213 (104 black; 109 white) RA patients. Relationships of omentin levels with those of endothelial activation markers, ultrasound determined carotid intima-media thickness and plaque, and matrix metalloproteinase (MMP)-2, -3 and -9 that mediate altered plaque stability, were identified in confounder adjusted multivariate regression models. Omentin concentrations were inversely associated with MMP-3 levels [ß = -364 (0.113), p = 0.002]. This relationship was influenced by population origin, RA activity and the erythrocyte sedimentation rate and joint deformity count (interaction p value = 0.009, 0.04, 0.04 and 0.007, respectively). Accordingly, the omentin-MMP-3 concentration relationship was reproduced in white [ß (SE) = -0.450 (0.153), p = 0.0004)] but not black patients [ß (SE) = -0.099 (0.195), p = 0.6)], in participants with disease remission or mild disease activity [ß (SE) = -0.411 (0.139), p = 0.004] but not with moderate or severe RA activity [ß (SE) = -0.286 (0.202), p = 0.2], and in those with a small [ß (SE) = -0.534 (0.161), p = 0.001] but not large erythrocyte sedimentation rate [-0.212 (0.168), p = 0.2] and without [ß (SE) = -0.554 (0.165), p = 0.0001] but not with large joint deformity counts [-0.110 (0.173), p = 0.5]. Omentin levels were unrelated to endothelial activation and atherosclerosis. Among patients with RA, a lack of plaque stabilizing effects by omentin may contribute to the reported link between severe disease and increased cardiovascular risk. The association between concentrations of omentin and MMP-3 is population specific in RA.
Assuntos
Artrite Reumatoide/sangue , Citocinas/sangue , Lectinas/sangue , Metaloproteinase 3 da Matriz/sangue , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Aterosclerose/sangue , Aterosclerose/complicações , Biomarcadores/sangue , População Negra , Sedimentação Sanguínea , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Índice de Gravidade de Doença , População BrancaRESUMO
OBJECTIVES: Our objective was to examine associations of traditional and non-traditional cardiovascular risk factors with relative leukocyte telomere length and confounder adjusted relationships of relative telomere length with endothelial activation and carotid atherosclerosis in black and white African patients with rheumatoid arthritis (RA). METHODS: Relative telomere length of leukocyte DNA in whole blood was determined using quantitative RT-PCR in 205 (101 black) African patients with RA. RESULTS: In demographic characteristic adjusted analysis, relative telomere length tended to be larger in black compared to white patients (median (IQR)=0.54 (0.42-0.54) and 0.48 (0.37-0.60) (p=0.07), respectively). In black patients, waist circumference, systolic, diastolic and mean blood pressure were associated with relative telomere length (ß (SE)=-0.00270 (0.00114) (p=0.02), -0.00185 (0.00060) (p=0.003), -0.00243 (0.00112) (p=0.03) and -0.00225 (0.00075) (p=0.003), respectively); in white patients, age, anti-cyclic citrullinated antibody positivity, biologic agent use, a cholesterol-HDL cholesterol ratio of >4 and the number of major traditional risk factors were related to relative telomere length (ß (SE) =-0.00242 (0.00113) (p=0.03), 0.06629 (0.03374) (p=0.05), -0.09321 (0.04310) (p=0.03), 0.08225 (0.03420) (p=0.02) and 0.04046 (0.01719) (p=0.02), respectively). One SD increase in relative telomere length was associated with carotid plaque (OR (95% CI)=1.65 (0.99-2.75) (p=0.05)) and vascular cell adhesion molecule-1 concentrations (ß (SE)=-0.05031 (0.02480) (p=0.04)) in black and white patients, respectively. CONCLUSIONS: This study disclosed paradoxically direct relationships between relative telomere length and cardiovascular risk factors in white and atherosclerosis in black African RA patients. The role of relative telomere length in cardiovascular risk and its stratification in RA requires longitudinal investigation.
Assuntos
Artrite Reumatoide/etnologia , População Negra , Doenças das Artérias Carótidas/etnologia , Endotélio Vascular/metabolismo , Homeostase do Telômero , Telômero/metabolismo , População Branca , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Biomarcadores/sangue , População Negra/genética , Fármacos Cardiovasculares/uso terapêutico , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/genética , Comorbidade , Fatores de Confusão Epidemiológicos , Estudos Transversais , Endotélio Vascular/efeitos dos fármacos , Feminino , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , África do Sul/epidemiologia , Telômero/efeitos dos fármacos , Telômero/genética , Homeostase do Telômero/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/sangue , População Branca/genéticaRESUMO
OBJECTIVES: We examined the association of TNF-related apoptosis-inducing ligand (TRAIL) concentrations with cardiovascular disease (CVD) in rheumatoid arthritis (RA) and, since osteoprotegerin (OPG) can act as a decoy receptor for TRAIL, whether TRAIL concentrations impact on the OPG level-atherosclerotic CVD relation that was recently documented in the present cohort. METHODS: TRAIL concentrations were assessed by ELISA in 151 RA patients of which 75 (49.7%) had CVD comprising ischaemic heart disease (n=27), cerebrovascular accident (n=26), peripheral artery disease (n=9) or/and heart failure (HF) (n=27), and 62 controls. RESULTS: Mean RA duration was 12 years. In RA patients, C-reactive protein (CRP) levels and cholesterol-HDL cholesterol ratio related to TRAIL concentrations [partial R=-0.222 (p=0.006) and 0.174 (p=0.04), respectively]. TRAIL concentrations were smaller in RA patients compared to controls (median (interquartile range) = 80.2 (60.9-120.4) versus 130.4 (89.4-167.7) pg/ml, p<0.0001)). TRAIL levels were larger in RA patients with compared to those without HF (105.5 (66.5-143.4) versus 79.9 (57.8-110.6), p=0.02); this difference was independent of demographic characteristics and traditional cardiovascular risk factors (p=0.04) but not CRP concentrations (p=0.1). TRAIL levels were consistently unrelated to atherosclerotic CVD. Our previously reported OPG-atherosclerotic CVD relation in RA survived adjustment for TRAIL concentrations in a mixed regression model (p=0.04). CONCLUSIONS: TRAIL concentrations are markedly reduced and associated with HF in established RA, this relationship being explained by CRP levels. OPG may directly enhance CVD risk in RA.
Assuntos
Artrite Reumatoide/metabolismo , Insuficiência Cardíaca , Isquemia Miocárdica , Osteoprotegerina/sangue , Doença Arterial Periférica , Acidente Vascular Cerebral , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Idoso , Aterosclerose/metabolismo , Proteína C-Reativa/análise , HDL-Colesterol/sangue , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/metabolismo , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/metabolismo , Análise de Regressão , Fatores de Risco , Espanha , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismoRESUMO
We examined the potential impact of demographic characteristics on the independent leptin-metabolic cardiovascular risk factor and leptin-endothelial activation relationships in black and white patients with RA. Leptin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 were measured in 217 RA patients (51.6% black). We determined associations in potential confounder and mediator-adjusted mixed regression models. No independent associations between leptin concentrations and cardiovascular risk were present in all patients and either women and men or black and white patients. However, age impacted on several leptin-cardiovascular risk relations (interaction P < 0.05). In patients aged <50 years (lower quartile), after but not before adjustment for waist circumference and body mass index in addition to other confounders, leptin concentrations associated with overall endothelial activation as estimated by an SD (z) score of endothelial activation molecule concentrations (partial R = 0.341, P = 0.04). In patients aged 50-58 years (second quartile), leptin concentrations related to those of HDL cholesterol (partial R = -0.365, P = 0.01) and total cholesterol-HDL cholesterol ratio (partial R = 0.299, P = 0.04), and in those aged 59-63 years (third quartile), paradoxically related to low systolic and mean blood pressure (partial R = -0.438, P = 0.005 and partial R = -0.370, P = 0.02, respectively). Patients with RA aged <50 years experience an independent adiposity-driven leptin-endothelial activation relationship in the absence of leptin-metabolic risk factor associations. Young but not older patients with RA may sustain obesity-induced endothelial activation that is directly mediated by leptin.
Assuntos
Envelhecimento/sangue , Artrite Reumatoide/sangue , Aterosclerose/sangue , Cardiopatias/epidemiologia , Leptina/sangue , Doenças Metabólicas/epidemiologia , Adulto , Fatores Etários , Idoso , Artrite Reumatoide/etnologia , Aterosclerose/etnologia , Biomarcadores/sangue , População Negra , Quimiocina CCL2/sangue , HDL-Colesterol/sangue , Comorbidade , Estudos Transversais , Selectina E/sangue , Feminino , Cardiopatias/etnologia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Doenças Metabólicas/etnologia , Pessoa de Meia-Idade , Fatores de Risco , Molécula 1 de Adesão de Célula Vascular/sangue , População BrancaRESUMO
In the present study, we examined the potential impact of adiponectin on carotid ultrasound determined atherosclerosis in 210 (119 black and 91 white) RA patients in mixed regression models. Total adiponectin concentrations were smaller in patients with compared to those without the metabolic syndrome (MetS) defined waist criterion (median (range) = 6.47 (1.23-34.54) versus 8.38 (0.82-85.30) ng/mL, P = 0.02, resp.); both total and high molecular weight (HMW) adiponectin concentrations were larger in patients with compared to those without joint deformities (7.97 (0.82-85.30) and 3.51 (0.01-35.40) versus 5.36 (1.29-19.49) and 2.34 (0.01-19.49) ng/mL, P = 0.003 and 0.02, resp.). Total and HMW adiponectin concentrations were associated with carotid artery plaque in patients with MetS waist (odds ratio (95% CI) = 0.87 (0.76-0.99) and 0.92 (0.85-0.99) per 1-standard deviation increment, P = 0.02 for both) and those without joint deformities (odds ratio (95% CI) = 0.94 (0.88-0.99) and 0.94 (0.89-0.99), P = 0.03 for both). Plaque prevalence was lower in patients without compared to those with joint deformities (23.4% versus 42.6, P = 0.004 in multivariable analysis). In RA patients with abdominal obesity or no clinically evident joint damage, adiponectin concentrations are reduced but nevertheless associated with decreased carotid atherosclerosis.
Assuntos
Adiponectina/metabolismo , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/patologia , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.
Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Cardiovasculares , Inflamação , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Idoso , Biomarcadores , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
We examined the potential impact of conventional compared with nonconventional cardiovascular risk factors including interleukin-6 levels on endothelial activation in RA. Circulating soluble E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 concentrations were measured in 217 African patients (112 black and 105 white) with RA. In comprehensive confounder adjusted mixed regression models, 5 conventional and 4 nonconventional cardiovascular risk factors were associated (P = 0.05 to <0.0001) with endothelial activation. Interleukin-6 was the only risk factor related to each endothelial activation molecule and independently contributed by 18% and significantly more than other risk factors to the variation in overall endothelial activation as estimated by an SD (z) score of endothelial activation molecule concentrations. The independent interleukin-6-overall endothelial activation relationships were reproduced in various subgroups. Interleukin-6 concentrations relate consistently, markedly, and to a larger extent than other cardiovascular risk factors to endothelial activation in RA. Assessment of interleukin-6 concentrations may enhance cardiovascular risk stratification in RA.
Assuntos
Artrite Reumatoide/complicações , Endotélio Vascular/fisiologia , Interleucina-6/sangue , Adulto , Idoso , Artrite Reumatoide/sangue , Sedimentação Sanguínea , Doenças Cardiovasculares/etiologia , Quimiocina CCL2/sangue , Receptores ErbB/fisiologia , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Resistina/sangue , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
BACKGROUND: In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics. METHODS: RA patients aged 30-70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up. RESULTS: A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15-32% of patients. C-statistics ranged 0.68-0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results. CONCLUSIONS: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de RiscoAssuntos
Artrite Reumatoide/sangue , Doenças das Artérias Carótidas/sangue , Contagem de Leucócitos , Resistina/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etnologia , Artrite Reumatoide/imunologia , Biomarcadores/sangue , População Negra , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/etnologia , Doenças das Artérias Carótidas/imunologia , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , África do Sul/epidemiologia , Regulação para Cima , População BrancaRESUMO
Rheumatoid arthritis (RA) impacts arterial and diastolic function. This study examined whether arterial properties can determine diastolic function in RA. In 173 RA patients, arterial function measures including carotid femoral pulse wave velocity (PWV), central systolic and pulse pressure, pulse pressure amplification, and the magnitude and timing of the forward and reflected waves were measured using applanation tonometry. Diastolic function parameters including the ratio of early-to-late transmitral velocity (E/A) and ratio of E to the mean of the lateral and septal wall myocardial tissue lengthening (e') were measured using echocardiography. The timing of the reflected wave was associated with E/A; PWV was related to E/e'. The timing of the reflected wave, forward wave magnitude, and pulse pressure amplification were associated with impaired relaxation; PWV was related to increased left ventricular (LV) filling pressure. Early wave reflection and PWV are associated with LV-impaired relaxation and increased filling pressure, respectively, in RA.
Assuntos
Artrite Reumatoide/complicações , Velocidade da Onda de Pulso Carótido-Femoral , Ecocardiografia Doppler , Doença Arterial Periférica/diagnóstico , Rigidez Vascular , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Diástole , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic pressure (CSP), central pulse pressure (CPP), peripheral pulse pressure (PPP), pulse pressure amplification (PPamp), and forward wave pressure (Pf)) among 170 RA patients without cardiovascular disease. In multivariable regression models, apelin concentrations were not independently associated with arterial function measures (p ≥ 0.15) in all patients. Inflammation markers were not consistently associated with apelin levels but joint deformity counts, Disease Activity Score in 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) impacted apelin-pressure pulsatility relations (interaction p ≤ 0.05). In stratified analysis, apelin was associated with CSP (partial r = - 0.33, p = 0.01), CPP (partial r = - 0.26, p = 0.04), PPamp (partial r = 0.27, p = 0.03), and Pf (partial r = - 0.33, p = 0.01) in patients without but not with joint deformities; apelin was related to CSP (partial r = - 0.24, p = 0.05) in those with a DAS28 joint < 2.8 (median value) (partial r = - 0.24, p = 0.05) but not ≥ 2.8, and to CSP (partial r = - 0.36, p = 0.003) in those with an erythrocyte sedimentation rate < 13 mm/h (median value) but not ≥ 13 mm/h. Apelin is associated with reduced pressure pulsatility in RA patients without but not with a high inflammatory burden. A loss of apelin protective effects on arterial function may contribute to the link between RA severity and cardiovascular risk.
Assuntos
Apelina/sangue , Artrite Reumatoide/fisiopatologia , Rigidez Vascular , Idoso , Artrite Reumatoide/sangue , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Índice de Gravidade de Doença , Função Ventricular EsquerdaRESUMO
Nesfatin is an anti-inflammatory molecule that reduces atherosclerotic cardiovascular risk. By contrast, visfatin has pro-inflammatory properties and is pro-atherogenic. We examined the potential impact of nesfatin and visfatin on atherosclerotic disease in 232 (113 black and 119 white) consecutive rheumatoid arthritis (RA) patients from 2 centers. Independent relationships of nesfatin and visfatin concentrations with metabolic risk factors, endothelial activation, carotid atherosclerosis and altered plaque stability were determined in multivariable regression models. Rheumatoid factor (RF) positivity was associated with both nesfatin (ßâ¯=â¯0.650, pâ¯<â¯0.0001) and visfatin levels (ßâ¯=â¯0.157, pâ¯=â¯0.03). Visfatin concentrations were related to increased diastolic blood pressure (ßâ¯=â¯4.536, pâ¯=â¯0.01) and diabetes prevalence (ßâ¯=â¯0.092, pâ¯=â¯0.04). Nesfatin levels were associated with reduced carotid intima-media thickness (ßâ¯=â¯-0.017, pâ¯=â¯0.008). Nesfatin (ßâ¯=â¯0.116, pâ¯=â¯0.001) and visfatin concentrations (ßâ¯=â¯0.234, pâ¯=â¯0.001) were related to those of matrix metalloproteinase-2 (MMP-2), a plaque stability mediator. Nesfatin and visfatin concentrations were directly correlated (Spearman's rhoâ¯=â¯0.516). The nesfatin-MMP-2 and visfatin-MMP-2 relations were both stronger in RF negative compared to RF positive patients (interaction pâ¯=â¯0.01 and pâ¯=â¯0.04, respectively). Nesfatin is associated with reduced atherosclerosis and increased plaque stability mediator levels in RA. Visfatin is related to adverse cardio-metabolic risk in RA. Increased MMP-2 expression in relation to visfatin may represent a compensatory mechanism aimed at reducing cardiovascular risk in RA.
Assuntos
Artrite Reumatoide/sangue , Aterosclerose/sangue , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a DNA/sangue , Proteínas do Tecido Nervoso/sangue , Nicotinamida Fosforribosiltransferase/sangue , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Índice de Massa Corporal , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Feminino , Regulação da Expressão Gênica/genética , Taxa de Filtração Glomerular , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Nucleobindinas , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Fator Reumatoide/sangue , Fatores de RiscoRESUMO
OBJECTIVE: Arterial properties influence cardiovascular disease (CVD) risk. We identified potential determinants of arterial function in patients with rheumatoid arthritis (RA). METHODS: Relationships of traditional cardiovascular risk factors and RA characteristics with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic and pulse pressure, peripheral pulse pressure, pulse pressure amplification, and forward wave pressure) were identified in multivariable backward regression models among 177 patients without established CVD (118 white, 32 Asian, 22 black, 5 mixed ancestry). RESULTS: Recorded characteristics explained 37% (pulse wave velocity) to 71% (reflected wave pressure) of the variability in arterial function. These factors were particularly associated with wave reflection and pressure pulsatility: RA duration (p = 0.04), rheumatoid factor status (p = 0.01 to 0.03), leukocyte counts (p = 0.02 to 0.05), and total cholesterol (p < 0.01 to 0.03). Body mass index (p < 0.01 to 0.02) and insulin resistance (p < 0.01 to 0.01) were related to reduced wave reflection and peripheral pulse pressure. Exercise (p = 0.02) and alcohol consumption (p < 0.01) were associated with increased pulse pressure amplification and decreased peripheral pulse pressure, respectively. Tumor necrosis factor-α inhibition (p < 0.01) was related to reduced pulse wave velocity, and tetracycline use (p = 0.02) to decreased peripheral pulse pressure. CONCLUSION: Traditional cardiovascular risk factors and disease characteristics are consistently associated with vascular hemodynamic alterations in RA. The relative effect of arterial stiffness, wave reflection, and pressure pulsatility on CVD risk in RA needs further study.
Assuntos
Artérias/fisiopatologia , Artrite Reumatoide/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Hemodinâmica/fisiologia , Rigidez Vascular/fisiologia , Adulto , Idoso , Artrite Reumatoide/complicações , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA. METHODS: Apelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis. RESULTS: In all patients, apelin concentrations were directly associated with those of MMP-2 (ß (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (ß (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (ß (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (ß (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (ß (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (ß (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (ß (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (ß (SE) = 0.015 (0.112), p = 0.7). CONCLUSIONS: Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.
Assuntos
Artrite Reumatoide/sangue , Doenças das Artérias Carótidas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Placa Aterosclerótica , Idoso , Apelina , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etnologia , Doenças Assintomáticas , Biomarcadores/sangue , População Negra , Sedimentação Sanguínea , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etnologia , Doenças das Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Modelos Lineares , Modelos Logísticos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Ruptura Espontânea , África do Sul/epidemiologia , População BrancaRESUMO
This study compared the estimated prevalence and potential determinants of left ventricular (LV) diastolic dysfunction upon applying different classification criteria in rheumatoid arthritis (RA). LV diastolic function was assessed echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e', lateral and septal e'), and left atrial volume index in 176 RA patients. Relationships of traditional cardiovascular risk factors and RA characteristics with LV diastolic function and dysfunction according to previous and current criteria were determined in multivariate regression models. Waist-hip ratio was associated with E/A (standardised ß (SE) = -0.28 ± 0.09, p = 0.0002) and lateral e' (standardised ß (SE) = 0.26 ± 0.09, p = 0.01); low diastolic blood pressure was related to E/e' (standardised ß (SE) = -0.16 ± 0.08, p = 0.04). Diastolic dysfunction prevalence differed upon applying previous (59%) compared to current (22%) criteria (p < 0.0001). One SD increase in waist-hip ratio was associated with diastolic dysfunction when applying current criteria (OR = 2.61 (95% CI = 1.51-4.52), p = 0.0006), whereas one SD increase in diastolic blood pressure was inversely related to diastolic dysfunction upon using previous criteria (OR = 0.57 (95% CI = 0.40-0.81), p = 0.002). In conclusion, application of current and previous diastolic dysfunction criteria markedly alters the prevalence and risk factors associated with diastolic dysfunction in RA.
RESUMO
OBJECTIVE: We determined the performance of the Framingham score and the Systematic COronary Risk Evaluation (SCORE) in assessing high-risk atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: We assembled 330 cases without established cardiovascular disease (CVD), diabetes, and moderate or severe chronic kidney disease among 451 consecutive Spanish patients who underwent CVD risk screening and carotid ultrasound-determined plaque assessment. The findings were validated in 90 black and 97 white African patients. RESULTS: When sensitivity for the Framingham score was set at 80% in receiver-operator curve analysis [area under the curve (AUC) = 0.799], the corresponding cutoff value and specificity were 7.3% and 63%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 10.8% and 65%, respectively. When sensitivity for SCORE (AUC = 0.747) was set at 80%, the cutoff value and specificity were 0.5% and 58%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 1.5% and 50%, respectively. Upon applying a cutoff value of 7.3% for the Framingham and 0.5% for SCORE in African white patients with RA, the corresponding sensitivities and specificities were 67% and 72%, and 67% and 55%, respectively. CVD risk equations did not discriminate between black African patients with and without plaque (AUC = 0.544 and 0.549 for Framingham score and SCORE, respectively). CONCLUSION: The Framingham score and SCORE at markedly low cutoff values of 7.3% to 10.8% and 0.5% to 1.5%, respectively, can usefully estimate plaque presence in RA. Effective population-specific CVD risk assessment strategies are needed in black African patients with RA.
Assuntos
Artrite Reumatoide/complicações , Aterosclerose/diagnóstico , Placa Aterosclerótica/diagnóstico , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , População Negra , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade , População BrancaRESUMO
OBJECTIVE: To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA). METHODS: We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients. RESULTS: The CKD-EPI eGFR was <90 ml/min/1.73m2 in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28-3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold. CONCLUSION: Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients.