RESUMO
AIM: We hypothesized that arterial function and N-terminal natriuretic peptide (NT-proBNP) levels as a marker of volume overload, relate differently to E/e' as an index of diastolic function in dialysis compared with non-dialysis patients with chronic kidney disease. We further examined whether cardiovascular risk factors attenuated these relationships. METHODS: We assessed cardiovascular risk factors and determined arterial function indices by applanation tonometry using SphygmoCor software and E/e' by echocardiography in 103 (62 non-dialysis and 41 dialysis) patients. RESULTS: In established confounder adjusted analysis, dialysis status impacted the pulse wave velocity-E/e' relationship (interaction p = .01) but not the NT-proBNP level-E/e' association (interaction p = .1). Upon entering arterial function measures and NT-proBNP levels simultaneously in regression models, arterial function measures were associated with E/e' (p = .008 to .04) in non-dialysis patients whereas NT-proBNP levels were related to E/e' in dialysis patients (p = .009 to .04). Bivariate associations were found between diabetes (p < .0001) and E/e' in non-dialysis patients, and haemoglobin concentrations and E/e' (p = .02) in those on dialysis. Upon adjustment for diabetes in non-dialysis patients, only central pulse pressure remained associated with E/e' (p = .02); when haemoglobin concentrations were adjusted for in dialysis patients, NT-proBNP levels were no longer associated with E/e' (p = .2). In separate models, haemoglobin levels were associated with E/e' independent of left ventricular mass index and preload and afterload measures (p = .02 to .03). CONCLUSION: The main determinants of E/e' may differ in non-dialysis compared with dialysis patients. These include arterial function and diabetes in non-dialysis patients, and volume overload and anaemia in dialysis patients.
Assuntos
Doenças Cardiovasculares/sangue , Diálise , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Diálise Renal , Insuficiência Renal Crônica/complicações , Função Ventricular Esquerda/fisiologia , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Diástole , Ecocardiografia/métodos , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Precursores de Proteínas , Análise de Onda de Pulso/métodos , Curva ROC , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapiaRESUMO
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
Objectives: Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2. Methods: Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index. Results: Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP). Conclusion: The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population.
Assuntos
Algoritmos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Adulto , Distribuição por Idade , Idoso , Canadá , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Internacionalidade , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Noruega/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , África do Sul/epidemiologia , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
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: The impact of metabolic risk factors on atherosclerotic cardiovascular disease (ACVD) in patients with rheumatoid arthritis (RA) from developing populations is currently unknown. We examined the relationships of the metabolic syndrome (MetS) and its components with carotid artery atherosclerosis in African women with rheumatoid arthritis (RA) from a developing black and developed Caucasian population. METHODS: We assessed the associations of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) defined MetS and its criteria with high resolution B-mode ultrasound determined common carotid artery intima-media thickness (cIMT) and carotid artery plaque in multivariable regression models in 104 black and 93 Caucasian women with RA. RESULTS: The MetS prevalence was 30.8% in black compared to 9.7% in Caucasian women with RA (adjusted odds ratio [95% confidence interval]=10.11 [1.76-58.03] [p=0.009]). Population origin impacted on the relationships of metabolic risk factors with atherosclerosis. In Caucasian women, the MetS was associated with cIMT (p=0.036) and MetS triglycerides and the number of MetS criteria were each associated with both cIMT (p=0.01 and p=0.028, respectively) and plaque (p=0.049 and p=0.02, respectively); by contrast, in black women, MetS blood pressure was related to cIMT (p=0.04). CONCLUSIONS: A high overall metabolic cardiovascular risk burden as disclosed by markedly prevalent MetS in women with RA from developing groups of black African descent was not associated with atherosclerosis. This calls for systematic rigorous cardiovascular risk management irrespective of metabolic risk factor profiles in African black women with RA.
Assuntos
Artrite Reumatoide/etnologia , População Negra/estatística & dados numéricos , Doenças das Artérias Carótidas/etnologia , Síndrome Metabólica/etnologia , População Branca/estatística & dados numéricos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Pressão Sanguínea , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Estudos Transversais , Países em Desenvolvimento , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , África do Sul/epidemiologiaRESUMO
Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.
Assuntos
Adipocinas/sangue , Artrite Reumatoide/sangue , Doenças Cardiovasculares/sangue , Adiponectina , Idoso , Pressão Arterial/fisiologia , Aterosclerose/sangue , Doenças das Artérias Carótidas/sangue , Espessura Intima-Media Carotídea , HDL-Colesterol/sangue , Feminino , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
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: Whether differential effects of volume load on left ventricular mass (LVM) and function occur in sustained volume-dependent primary hypertension, and the impact of atrial natriuretic peptide (ANP) on these effects, is unknown. Methods: From aortic pressure, velocity and diameter measurements and echocardiography, we determined in an African community (n = 772), the impact of systemic flow-induced increases in central pulse pressure (PPc) and circulating ANP (ELISA) on LVM and indexes of function. Results: Stroke volume (SV), but not aortic flow (Q), was associated with LVM and mean wall thickness (MWT) beyond stroke work and confounders (p < 0.0001). Adjustments for SV markedly decreased the relationships between PPc and LVMI or MWT. However, neither SV, nor Q were independently associated with either myocardial s', e', or E/e' (p > 0.14) and adjustments for neither SV nor Q modified relationships between PPc and s', e' or E/e' (p < 0.005 to <0.0001). SV was nevertheless strongly and independently associated with ANP (p < 0.0001) and ANP was similarly strikingly associated with s' (p < 0.0001) and e' (p < 0.0005), but not E/e', independent of confounders and several determinants of afterload. Importantly, ANP concentrations were inversely rather than positively associated with LV diastolic dysfunction (DD) (p < 0.005) and lower rather than higher ANP concentrations contributed markedly to the ability to detect DD in those with, but not without LV hypertrophy. Conclusion: In populations with sustained volume-dependent hypertension, flow (SV)-related increases in PP have a major impact on LV structure, but not on function, an effect attributed to parallel striking beneficial actions of ANP on myocardial function.
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BACKGROUND: Whether systolic blood pressure (SBP) control in sustained volume-dependent primary hypertension is associated with blunted ANP (atrial natriuretic peptide) relationships with indexes of volume load is unknown. METHODS: Systemic hemodynamics (central pressure, echocardiographic aortic velocity and diameter measurements in the outflow tract), circulating ANP concentrations (ELISA assays) and glomerular and tubular function (24-hour urine collections [n=519]) were determined in a community of African ancestry (n=772). RESULTS: As compared with those with a controlled SBP, those with an uncontrolled SBP (n=198) showed lower ANP concentrations (P<0.005) despite higher stroke volume and cardiac output (P<0.0001) and renal differences consistent with enhanced fluid retention. In those with a controlled SBP, fractional Na+ excretion (FeNa+; P<0.0005) and creatinine clearance (glomerular filtration rate; P<0.005) were inversely associated with ANP concentrations independent of confounders. Moreover, in those with a controlled SBP, stroke volume and cardiac output (P<0.0001) were independently and positively associated with ANP concentrations. In addition, in those with a controlled SBP, ANP concentrations were independently and inversely associated with systemic vascular resistance (SVR; P<0.0001) and aortic characteristic impedance (Zc; P<0.005). By contrast, in those with uncontrolled SBP, no relationships between either stroke volume (P>0.25), cardiac output (P>0.29), FeNa+ (P>0.77), or glomerular filtration rate (P>0.47) and ANP concentrations were noted. Furthermore, in those with an uncontrolled SBP, no relationships between ANP concentrations and SVR or Zc were observed (P>0.34). CONCLUSIONS: In a population where primary hypertension is strongly volume-dependent, those with an uncontrolled SBP have an attenuated relationship between ANP and both renal and hemodynamic indexes of volume overload and the vascular effects of ANP.
Assuntos
Fator Natriurético Atrial , Humanos , Hipertensão EssencialRESUMO
Cardiovascular diseases, including ischemic heart disease and stroke, reportedly comprise the top two causes of global mortality [...].
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PURPOSE: We assessed whether aortic stiffness and pulsatile pressures can mediate chronic kidney disease (CKD)-associated impaired diastolic function. PARTICIPANTS AND METHODS: In 276 black Africans including 46 CKD (19 non-dialysis; 27 dialysis) and 230 control subjects, pulse wave velocity (PWV) estimated aortic stiffness and pulsatile pressures (forward and backward wave pressure, central systolic blood pressure (CSBP) and pulse pressure (CPP)) were determined by applanation tonometry; e' as an index of left ventricular active relaxation and E/e' as a measure of left ventricular filling pressure or passive relaxation were evaluated by echocardiography. RESULTS: In age, sex, traditional cardiovascular risk factor and mean arterial pressure (MAP) adjusted regression models, CKD was inversely associated with e' (p = 0.03) and directly with E/e' (p < 0.01). The CKD-e' relationship was attenuated and no longer significant (p = 0.31) upon additional adjustment for aortic PWV but not pulsatile pressures (p = 0.03-0.05). In product of coefficient mediation analysis, PWV accounted for 47.6% of the CKD-e' association. CSBP (22.9%) and CPP (18.6%) but not PWV (11.3%) accounted for a significant and relevant proportion of the CKD-E/e' relationship. However, CKD remained strongly associated with E/e' independent of aortic function measures (p < 0.01). Treatable covariates that were or tended to be consistently associated with diastolic function included MAP (p < 0.01) and diabetes (p = 0.02-0.07) for the CKD-e' and CKD-E/e' relations, respectively. CONCLUSION: Aortic stiffness rather than pulsatile pressures mediates CKD-related impaired left ventricular active relaxation. By contrast, aortic pulsatile pressures (and not stiffness) contribute to CKD-related left ventricular filling pressures but do not fully account for the respective association.
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Introduction: Circulating uric acid, ferritin, albumin, intact parathyroid hormone and gamma-glutamyl transferase each participate in biochemical reactions that reduce or/and enhance oxidative stress, which is considered the final common pathway through which pathophysiological mechanisms cause uremic cardiomyopathy. We hypothesized that the respective biomarkers may be involved in the development of uremic cardiomyopathy characteristics and can be useful in their identification among chronic kidney disease patients. Methods: We assessed traditional and non-traditional cardiovascular risk factors including biomarker concentrations and determined central systolic blood pressure using SphygmoCor software and cardiac structure and function by echocardiography in 109 (64 non-dialysis and 45 dialysis) patients. Associations were evaluated in multivariate regression models and receiver operator characteristic (ROC) curve analysis. Results: Each biomarker concentration was associated with left ventricular mass beyond stroke work and/or inappropriate left ventricular mass in all, non-dialysis and/or dialysis patients. Ferritin, albumin and gamma-glutamyl transferase levels were additionally associated with E/e' in all, non-dialysis and/or dialysis patients. Dialysis status influenced the relationship of uric acid concentrations with inappropriate left ventricular mass and those of gamma-glutamyl transferase levels with left ventricular mass and inappropriate left ventricular mass. In stratified analysis, low uric acid levels were related to inappropriate left ventricular mass in dialysis but not non-dialysis patients (interaction p=0.001) whereas gamma-glutamyl transferase concentrations were associated with left ventricular mass and inappropriate left ventricular mass in non-dialysis but not dialysis patients (interaction p=0.020 to 0.036). In ROC curve analysis, uric acid (area under the curve (AUC)=0.877), ferritin (AUC=0.703) and albumin (AUC=0.728) concentrations effectively discriminated between dialysis patients with and without inappropriate left ventricular hypertrophy, left ventricular hypertrophy, and increased E/e,' respectively. Conclusion: Uric acid, ferritin, albumin, parathyroid hormone and gamma-glutamyl transferase were associated with uremic cardiomyopathy characteristics and could be useful in their identification. Our findings merit validation in future longitudinal studies.
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METHODS: Cardiovascular risk factors, aortic and cardiac function, atherosclerosis extent, and cardiovascular event rates were assessed in 115 consecutive predialysis (n = 67) and dialysis patients (n = 48) including 46 black and 69 other (32 Asian, 28 white, and 9 mixed race) participants. Data were analysed in multivariable regression models. RESULTS: Overall, black compared to other African CKD patients had less frequent carotid artery plaque (OR (95% CI) = 0.38 (0.16-0.91)) despite an increased cardiovascular risk factor burden. In receiver operator characteristic curve analysis, the Framingham score performed well in identifying non-black but not black CKD patients with carotid plaque (area under the curve (AUC) (95% CI) = 0.818 (0.714-0.921) and AUC (95% CI) = 0.556 (0.375-0.921), respectively). Black compared to other African predialysis patients experienced larger Framingham scores and more adverse nontraditional cardiovascular risk factors, impaired arterial and diastolic function but similar cardiovascular event rates (OR (95% CI) = 0.93 (0.22 to 3.87)). Among dialysis patients, black compared to other Africans had an overall similar traditional and nontraditional cardiovascular risk factor burden, similar arterial and diastolic function but increased systolic function (partial R = 0.356, p = 0.01 and partial R = 0.315, p = 0.03 for ejection fraction and stroke volume, respectively) and reduced cardiovascular event rates (OR (95% CI) = 0.22 (0.05 to 0.88)). CONCLUSION: Black compared to other African CKD patients have less frequent very high risk atherosclerosis and experience weaker cardiovascular risk factor-atherosclerotic CVD relationships. These disparities may be due to differences in epidemiological health transition stages. Among dialysis patients, black compared to other Africans have less cardiovascular events, which may represent a selection bias as previously documented in black Americans.
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INTRODUCTION: We hypothesized that post transplantation anaemia and persistent secondary hyperparathyroidism are potential determinants of diastolic function in stable kidney transplant recipients. METHODS: We assessed traditional and non-traditional cardiovascular risk factors and determined carotid artery intima-media thickness and plaque by ultrasound, arterial function by applanation tonometry using SphygmoCor software and diastolic function by echocardiography in 43 kidney transplant recipients with a transplant duration of ≥6 months, no acute rejection and a glomerular filtration rate of ≥15 mL/min/1.73m2. RESULTS: Mean (SD; range) transplant duration was 12.3 (8.0; 0.5-33.8) years. Post transplantation anaemia and persistent secondary hyperparathyroidism were identified in 27.9% and 30.8% of the patients, respectively; 67.5% of the participants were overweight or obese. In established confounder adjusted analysis, haemoglobin (partial R=-0.394, p=0.01) and parathyroid hormone concentrations (partial R=0.382, p=0.02) were associated with E/e'. In multivariable analysis, haemoglobin (partial R=-0.278, p=0.01) and parathyroid levels (partial R=0.324, p=0.04) were independently associated with E/e'. Waist-height ratio (partial R=-0.526, p=0.001 and partial R=-0.355, p=0.03), waist circumference (partial R=-0.433, p=0.008 and partial R=-0.393, p=0.02) and body mass index (partial R=-0.332, p=0.04 and partial R=-0.489, p=0.002) were associated with both e' and E/A, respectively, in established confounder adjusted analysis. The haemoglobin-E/e' (partial R=-0.422, p=0.02), parathyroid hormone-E/e' (partial R=0.434, p=0.03), waist-height ratio-e' (partial R=-0.497, p=0.007) and body mass index-E/A (partial R=-0.386, p=0.04) relationships remained consistent after additional adjustment for left ventricular mass index and cardiac preload and afterload measures. CONCLUSION: Haemoglobin and parathyroid hormone concentrations as well as adiposity measures are independently associated with diastolic function in kidney transplant recipients. Whether adequate management of post transplantation anaemia, persistent secondary hyperparathyroidism and excess adiposity can prevent the development of heart failure with preserved ejection fraction in kidney transplant recipients merits further investigation.