Serum Uric Acid Levels and Subclinical Atherosclerosis: Results From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

High serum uric acid (sUA) has been associated with coronary artery calcium (CAC) and increased carotid intima-media thickness (cIMT) in people at high cardiovascular risk. However, association is unclear in apparently healthy individuals. Our study aims to evaluate association between sUA and subclinical atherosclerosis measures: CAC and increased cIMT, in apparently healthy adults enrolled in ELSA-Brasil. A total of 4096 participants without previous coronary artery disease, stroke, and use of urate-lowering drugs, underwent CAC and cIMT assessment. All analyses were stratified by sex. Serum uric acid categorized by quintiles was the exposure variable. Thorough cardiovascular risk factor evaluation was performed, and association between sUA quintiles and CAC and cIMT was analyzed by linear regression using ln(CAC + 1) and cIMT, both as continuous variables. Median age of the sample was 49.0 (44.0-56.0) years (women: 55.1%; 59.1% were white). Mean values of sUA were 6.5 ± 1.4 mg/dL for men, and 4.9 ± 1.2 mg/dL for women. The highest quintile (Q5) of sUA was independently associated with cIMT in women (beta-coefficient: 0.022; 95% CI: 0.007-0.036; P = 0.003) and men (beta-coefficient: 0.020; 95% CI: 0.002-0.038; P = 0.032). Regarding CAC, no association was found: men's Q5 (beta-coefficient: -0.142; 95% CI: -0.436 to 0.153; P = 0.347) and women's Q5 (beta-coefficient: 0.046; 95% CI: -0.152 to 0.245; P = 0.647). In this cohort, the highest sUA quintiles were independently associated with cIMT in both women and men. No association was found between sUA and the presence of CAC.

Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility.

OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. RESULTS: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. CONCLUSION: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility / Associação entre o polimorfismo do gene PDCD1 e a susceptibilidade ao lúpus eritematoso sistêmico e à artrite reumatoide

ABSTRACT Objective: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05. Results: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. Conclusion: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

RESUMO Objetivo: Este estudo teve como objetivo analisar a relação entre o polimorfismo do gene PDCD1 (programmed cell death 1) (PD1.3G/A - rs11568821) com características do lúpus eritematoso sistêmico (LES) e da artrite reumatoide (AR) em uma população do sul do Brasil. Métodos: A técnica de PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Lenght Polymorphism) foi utilizada para analisar amostras de 95 pacientes com LES e 87 com AR, assim como em 128 indivíduos do grupo controle de Santa Catarina, sul do Brasil. Foi analisada a probabilidade de equilíbrio de Hardy-Weinberg (EHW) e a odds ratio (OR), considerando um IC 95% e p ≤ 0,05. Resultados: As frequências alélicas PD1.3 A foram de 0,095 (LES), 0,115 (AR) e 0,078 (controles). Os genótipos do grupo controle estavam em EHW, enquanto aqueles dos pacientes com LES e AR não estavam. No entanto, não foi encontrada associação entre o polimorfismo PD1.3 e a suscetibilidade ao LES ou à AR, nem com dados clínicos ou epidemiológicos. Conclusão: Não foi encontrada associação significativa entre o polimorfismo PD1.3 e a susceptibilidade ao LES ou à AR nessa população do sul do Brasil.

Association of PDCD1 polymorphism to Systemic Lupus Erythematosus and Rheumatoid Arthritis susceptibility. / Associação entre o polimorfismo do gene PDCD1 e a susceptibilidade ao lúpus eritematoso sistêmico e à artrite reumatoide.

OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS: Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg Equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. RESULTS: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. CONCLUSION: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

Axial gout is frequently associated with the presence of current tophi, although not with spinal symptoms.

STUDY DESIGN: Prospective cross-sectional study. OBJECTIVE: To analyze the association of tomographically identified axial gouty lesions with clinical and laboratory characteristics. SUMMARY OF BACKGROUND DATA: Axial gout might be more common than previously thought. The true relationship of these lesions to symptoms or other gout-associated features is poorly understood. METHODS: Forty-two patients with gout underwent thoracic and lumbar spine computed tomographic (CT) scans. CT scans were read by an experienced radiologist blinded to the features of the patients. Axial gout was defined as the presence of bony erosions, facet joints, or disc calcification and tophi in the axial skeleton. Epidemiological and clinical data were collected from medical records. At study entry, patients were evaluated for axial symptoms (back pain or neurological complaints) and subcutaneous tophi. The Fisher exact test and the Student t test were performed for statistical analyses of data. RESULTS: Twelve (29%) of the 42 patients had CT evidence of axial gout. Axial tophi were identified in 5 patients (12%), interapophyseal joints erosions or calcifications in 7 patients (17%), and discal abnormalities in 9 patients (21%). Lumbar spine involvement was a universal finding. Five patients (42%) had thoracic spine involvement and 2 patients (18%) had sacroiliac lesions. No association was found between symptoms and axial gout (P = 0.62). Duration of gout, mechanism of disease (overproduction vs. underexcretion), and metabolic comorbidities were not related to axial involvement. A higher prevalence of axial gout was found between patients with current peripheral tophi (67% vs. 30%; P = 0.03); however, no association was found in patients with a past history of tophi (P = 0.72). CONCLUSION: Our study demonstrated a high prevalence of axial gout not associated with spine symptoms. This finding introduces a differential diagnosis in axial lesions in patients with gout. In addition, the unique association with a current but not previous history of peripheral tophi suggests that gout treatment might be effective in preventing or solving gout axial lesions. LEVEL OF EVIDENCE: 3.

Gout in the spine.

Axial gout can affect all segments of the spine. It is manifested as back pain, as pain associated with neurological symptoms, and as neurological impairment without pain in 17.9%, 75.8% and 4.2% of cases, respectively. These manifestations were the first presentation of gout in many patients. Although x-rays as well as computed tomography and especially magnetic resonance scans can be very suggestive, histopathological, cytological and crystal analyses are the diagnostic gold standard. In most cases involving neurological manifestations, the patient underwent surgery, leading to satisfactory results. There are, however, some reports of full recovery following the usual clinical treatment for gout, suggesting that such treatment may be the initial option for those subjects with a history of gout and radiological findings of axial involvement.

Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis.

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Gota axial / Gout in the spine

A gota axial pode afetar todos os segmentos da coluna vertebral. Ela se manifesta como dor nas costas, dor associada com sintomas neurológicos, e como comprometimento neurológico sem dor em 17,9%, 75,8% e 4,2% dos casos, respectivamente. Essas manifestações foram a primeira apresentação da gota em muitos pacientes. Embora radiografias, bem como tomografia computadorizada e especialmente ressonância magnética, possam ser muito sugestivos, análises histopatológicas, citológicas e pesquisa de cristais são o padrão ouro de diagnóstico. Na maioria dos casos que envolveram manifestações neurológicas, o paciente foi submetido à cirurgia, levando a resultados satisfatórios. Há, no entanto, alguns relatos de recuperação total após o tratamento clínico habitual para gota, o que sugere que esse tratamento pode ser a opção inicial para os indivíduos com histórico de gota e sinais radiológicos de envolvimento axial.

Axial gout can affect all segments of the spine. It is manifested as back pain, as pain associated with neurological symptoms, and as neurological impairment without pain in 17.9%, 75.8% and 4.2% of cases, respectively. These manifestations were the first presentation of gout in many patients. Although x-rays as well as computed tomography and especially magnetic resonance scans can be very suggestive, histopathological, cytological and crystal analyses are the diagnostic gold standard. In most cases involving neurological manifestations, the patient underwent surgery, leading to satisfactory results. There are, however, some reports of full recovery following the usual clinical treatment for gout, suggesting that such treatment may be the initial option for those subjects with a history of gout and radiological findings of axial involvement.

Ausência de associação entre os polimorfismos do gene interleucina-18 e artrite reumatoide / Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis

OBJETIVO: Analisar a associação dos polimorfismos do gene interleucina-18 (IL-18) com artrite reumatoide (AR) e com fatores de risco de doenças cardiovasculares (DCV). MÉTODOS: A amostra foi constituída por 97 pacientes com AR e 151 controles saudáveis. Nos primeiros, foram analisados fatores de risco de DCV, tais como níveis do colesterol, hipertensão arterial, tabagismo e fator reumatoide, bem como o nível da proteína C-reativa (CRP). O DNA foi extraído e foram analisados os polimorfismos de nucleotídeo único (SNP) nas posições -607C/A e -137G/C do gene IL-18 em ambos os grupos. O equilíbrio de Hardy-Weinberg (EHW) e o odds ratio (OR) foram realizados, considerando IC 95% e P < 0,05. RESULTADOS: As frequências do alelo -607A nos pacientes com AR e nos controles foram de 0,443 e 0,424 e do alelo -137C foram de 0,304 e 0,291, respectivamente. As frequências do genótipo estavam em EHW, exceto em controles no locus -137 (P = 0,006). Não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com fatores de risco de DCV, incluindo o nível do colesterol e de CRP (P > 0,05). Além disso, observaram-se mais indivíduos fumantes entre pacientes com AR em comparação aos controles (OR = 1,691; P = 0,088), e os níveis de CRP eram ligeiramente mais elevados em pacientes fumantes quando comparados aos de pacientes não fumantes (OR = 2,673; P = 0,061). CONCLUSÕES: Ao analisar uma amostra de pacientes com AR no sul do Brasil, não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com os fatores de risco de DCV.

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Increased prevalence of simple renal cysts in patients with gout.

The aim of this study was to determine the prevalence of simple renal cysts in gout patients and evaluate associated risk factors for its development. Hundred and forty-six patients followed at our outpatient Gout Unit and 47 sex- and age-matched healthy kidney donors who had undergone routine renal ultrasonography, using a static gray scale and real-time B-mode units with a 3.5- or 5.0-MHz transducer, were evaluated for the presence of renal cysts. Demographic and clinical characteristics of gout patients were evaluated considering possible risk factors for the occurrence of simple renal cysts such as age, male gender, hypertension, and renal impairment. The prevalence of simple renal cyst was 26.0 % in gout patients and 10.6 % in control group (P = 0.045). Gout patients with simple renal cysts presented less renal lithiasis than those without this complication (5.2 vs 25.9 %; P = 0.003) in spite of an overall higher frequency of renal stones in gout patients compared to control group (20.5 vs. 6.3 %, P = 0.025). The presence of simple renal cyst in gout was not associated with previously reported factors such as age (P = 0.296), male predominance (P = 0.688), hypertension (P = 0.314), and renal impairment (P = 254). Moreover, no association with disease duration (P = 0.843) or tophi (P = 0.616) was observed. In conclusion, gout patients have an increased prevalence of simple renal cysts associated with a lower occurrence of nephrolithiasis. Whether renal cysts have any protective effect in the development of nephrolithiasis in gout remains to be determined.

Single measurements of C-reactive protein and disease activity scores are not predictors of carotid atherosclerosis in rheumatoid arthritis patients.

BACKGROUND: Although inflammation has a defined role in the pathogenesis of atherosclerosis, the link between rheumatoid arthritis (RA) parameters of disease activity and atherosclerotic findings are not defined. OBJECTIVE: To investigate the association between subclinical carotid atherosclerosis and clinical/laboratorial parameters of RA systemic inflammatory activity. METHODS: Seventy-one RA patients were consecutively selected and compared to 53 healthy controls. Smoking, diabetes and hypertension were excluded, as well as the use of statins or fibrates. B-mode carotid ultrasound was performed in all subjects. CRP, ESR and fibrinogen were determined in both groups. Clinical assessment of RA activity included DAS 28 and SDAI. Correlation between plaques and intima-media thickness (IMT) of common carotid arteries and inflammatory parameters was evaluated. RESULTS: Carotid plaques were more prevalent in RA patients than in controls (14.1% vs. 1.9 %, p=0.02) and marginally increased IMT was observed (0.72 +/- 0.17 vs. 0.67 +/- 0.15 mm, p=0.07). RA patients with plaques had older age (p=0.001) and increased IMT (p<0.001), but low SDAI (p=0.025) compared to those without plaques. RA patients with plaques had also longer disease duration, although this difference did not reach statistical significance (p=0.06). No significant correlations were found between IMT and ESR (p=0.80), CRP (p=0.75), fibrinogen (p=0.94), HAQ (p=0.89) and DAS 28 (p=0.13). CONCLUSIONS: Carotid atherosclerosis is more frequently detected in RA but its prevalence was not correlated with isolated inflammatory markers measurement or noncumulative activity scores. These findings reinforce the need to evaluate subclinical atherosclerosis in RA patients, and to find predictors of atherosclerotic lesions.