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Epidemiological investigations suggest that T102C polymorphism of gene 5-HT2A may be associated with mean life span because diseases and behaviors related to this polymorphism, such as schizophrenia, suicide, aggression, and addiction, may potentially shorten mean life span. A sample of 687 individuals without previous neuropsychiatric disease was genotyped and separated into 3 groups according to their gender and age: 14-45 years old, 46-64 years old and 65-100 years old. Molecular genotyping was performed using the technique of polymerase chain reaction followed by restriction fragment length polymorphism using HpaII restriction enzyme. 5-HT2A genotype frequencies were: TT = 21.5% (148), CC = 16.6% (114) and TC = 61.9% (425) and allele frequencies were T = 52.5% and C = 46.5%. Significant differences were found between mean age of the TT genotype carriers (60.27 ± 12.60 years) and TC genotype carriers (56.80 ± 13.18 years) of T102C polymorphism of gene 5-HT2A (P = 0.026) as well as the age groups (P = 0.012). Carriers of genotype TT were older than the other two genotypes, whereas carriers of genotype CC had an intermediate age compared with TT and CC subjects. The present results demonstrate an association between T102C polymorphism of gene 5-HT2A and age. Our results suggest that T102C polymorphism of gene 5-HT2A is associated with mean life span, and thus this gene becomes a possible candidate for the group of adaptive genes to meat consumption proposed in the literature. Further studies should be conducted in order to elucidate this association.

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We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1% cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580%/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319%/g) was greater than CE uptake (0.0595 ± 0.0207%/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.

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Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

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We investigated whether fibrin glue (FG) could promote urethral sphincter restoration in muscle-derived stem cell (MDSC)-based injection therapies in a pudendal nerve-transected (PNT) rat, which was used as a stress urinary incontinence (SUI) model. MDSCs were purified from the gastrocnemius muscles of 4-week-old inbred female SPF Wistar rats and labeled with green fluorescent protein. Animals were divided into five groups (N = 15): sham (S), PNT (D), PNT+FG injection (F), PNT+MDSC injection (M), and PNT+MDSC+FG injection (FM). Each group was subdivided into 1- and 4-week groups. One and 4 weeks after injection into the proximal urethra, leak point pressure (LPP) was measured to assess urethral resistance function. Histology and immunohistochemistry were performed 4 weeks after injection. LPP was increased significantly in FM and M animals after implantation compared to group D (P < 0.01), but was not different from group S. LPP was slightly higher in the FM group than in the M group but there was no significant difference between them at different times. Histological and immunohistochemical examination demonstrated increased numbers of surviving MDSCs (109 ± 19 vs 82 ± 11/hpf, P = 0.026), increased muscle/collagen ratio (0.40 ± 0.02 vs 0.34 ± 0.02, P = 0.044), as well as increased microvessel density (16.9 ± 0.6 vs 14.1 ± 0.4/hpf, P = 0.001) at the injection sites in FM compared to M animals. Fibrin glue may potentially improve the action of transplanted MDSCs to restore the histology and function of the urethral sphincter in a SUI rat model. Injection of MDSCs with fibrin glue may provide a novel cellular therapy method for SUI.

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Common variants of the transcription factor 7-like 2 (TCF7L2) gene have been found to be associated with type 2 diabetes in different ethnic groups. The Japanese-Brazilian population has one of the highest prevalence rates of diabetes. Therefore, the aim of the present study was to assess whether two single-nucleotide polymorphisms (SNPs) of TCF7L2, rs7903146 and rs12255372, could predict the development of glucose intolerance in Japanese-Brazilians. In a population-based 7-year prospective study, we genotyped 222 individuals (72 males and 150 females, aged 56.2 ± 10.5 years) with normal glucose tolerance at baseline. In the study population, we found that the minor allele frequency was 0.05 for SNP rs7903146 and 0.03 for SNP rs12255372. No significant allele or genotype association with glucose intolerance incidence was found for either SNP. Haplotypes were constructed with these two SNPs and three haplotypes were defined: CG (frequency: 0.94), TT (frequency = 0.027) and TG (frequency = 0.026). None of the haplotypes provided evidence for association with the incidence of glucose intolerance. Despite no associations between incidence of glucose intolerance and SNPs of the TCF7L2 gene in Japanese-Brazilians, we found that carriers of the CT genotype for rs7903146 had significantly lower insulin levels 2 h after a 75-g glucose load than carriers of the CC genotype. In conclusion, in Japanese-Brazilians, a population with a high prevalence of type 2 diabetes, common TCF7L2 variants did not make major contributions to the incidence of glucose tolerance abnormalities.

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Both genetic background and diet have profound effects on plasma lipid profiles. We hypothesized that a high-carbohydrate (high-CHO) diet may affect the ratios of serum lipids and apolipoproteins (apo) differently in subjects with different genotypes of the SstI polymorphism in the apoCIII gene (APOC3). Fifty-six healthy university students (27 males and 29 females, 22.89 ± 1.80 years) were given a washout diet of 54% carbohydrate for 7 days, followed by a high-CHO diet of 70% carbohydrate for 6 days without total energy restriction. Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB100, apoAI, and the APOC3 SstI polymorphism were analyzed. The ratios of serum lipids and apoB100/apoAI were calculated. At baseline, the TG/HDL-C ratio was significantly higher in females, but not in males, with the S2 allele. The differences in the TG/HDL-C ratio between genotypes remained the same after the washout and the high-CHO diet in females. When compared with those before the high-CHO diet, the TC/HDL-C (male S2 carriers: 3.13 ± 1.00 vs 2.36 ± 0.65, P = 0.000; male subjects with the S1S1 genotype: 2.97 ± 0.74 vs 2.09 ± 0.55, P = 0.000; female S2 carriers: 2.68 ± 0.36 vs 2.24 ± 0.37, P = 0.004; female subjects with the S1S1 genotype: 2.69 ± 0.41 vs 2.09 ± 0.31, P = 0.000) and LDL-C/HDL-C (male S2 carriers: 1.44 ± 0.71 vs 1.06 ± 0.26, P = 0.012; male subjects with the S1S1 genotype: 1.35 ± 0.61 vs 1.01 ± 0.29, P = 0.005; female S2 carriers: 1.18 ± 0.33 vs 1.00 ± 0.18, P = 0.049; female subjects with the S1S1 genotype: 1.18 ± 0.35 vs 1.04 ± 0.19, P = 0.026) ratios were significantly decreased after the high-CHO diet regardless of gender and of genotype of the APOC3 SstI polymorphism. However, in female S2 carriers, the TG/HDL-C (1.38 ± 0.46 vs 1.63 ± 0.70, P = 0.039) ratio was significantly increased after the high-CHO diet. In conclusion, the high-CHO diet has favorable effects on the TC/HDL-C and LDL-C/HDL-C ratios regardless of gender and of genotype of the APOC3 SstI polymorphism. Somehow, it enhanced the adverse effect of the S2 allele on the TG/HDL-C ratio only in females.

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The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross-sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5%), middle age (average 39 years), had a low educational level (60.4%), and low income (51.0%). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = ± 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3% pre- and 32.4% post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0% of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes.

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Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

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Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg−1·day−1), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.

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Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.

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Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

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Três linhagens genética suína A, B e C comercializadas no Brasil, foram submetidas ao insensibilizador elétrico manual (Karl Schermer 220-230/250 volts, 45-60 Hz e 1,4 - 1,5 A) e ao sistema gasoso coletivo (COMBI-BUTINA 90% CO2) . A insensibilização elétrica proporcionou níveis mais elevados de salpicamento nas regiões do coxão mole (0,477 e 0,26, p < 0,01), paleta/cranial (0,154 e 0,039, p < 0,05), paleta/central (0,261 e 0,052, p < 0,001), paleta/caudal (0,180 e 0,030, p < 0,01), lombo/central (0,185 e 0,065, p < 0,01), lombo/caudal (0,06 e 0,207, p < 0,01) e lombo/lateral externa (0,061 e 0,013, p < 0,05), assim como salpicamento mais difuso nas regiões do coxão-mole (0,461 e 0,279, p < 0,05), paleta/cranial (0,154 e 0,039, p < 0,01), paleta/central (0,231 e 0,039, p < 0,001) e paleta/caudal (0,185 e 0,026, p < 0,001). O sistema elétrico também proporcionou maiores índices de escoriações da pele nas regiões da paleta (1,098 e 0,795, p < 0,001), corpo (1,04 e 0,948, p < 0,05) e pernil (0,84 e 0,68, p < 0,001), assim como elevados índices de reflexo palpebral (11,57%) comparativamente ao gasoso (2,86%), de um total de 426 suínos. Pequenos índices de fraturas ósseas e contusões musculares em animais de ambos os sistemas foram observados.

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Foi avaliado o prazo de vida útil do queijo Minas frescal armazenado a 4 °C por 30 dias, através de análises microbiológicas e físico-químicas. Três lotes (A, B e C) de uma mesma marca foram analisados nos dias 1, 10, 20 e 30 após a fabricação. Foram feitas as contagens de microrganismos psicrotróficos, lipolíticos, proteolíticos, bactérias lácticas e mesófilas, que apresentaram um crescimento contínuo durante o período, atingindo contagens médias, respectivamente:, piscotróficos = 11,63; lipolíticos = 10,34; proteolíticos = 9,75 bactérias lácticas = 9,53; e mesófilos = 11,47 log UFC.g-1. A população de Escherichia coli desenvolveu-se em um dos lotes e Staphylococcus coagulase + e Salmonella não foram detectados. No mesmo período, observou-se a redução de 0,81 no valor do pH e o aumento do ácido láctico (0,026%). Não se observou redução na gordura (21,5%), embora a quantidade de ácidos graxos livres tenha aumentado em 0,22 mg KOH.g-1 de gordura. A proteína variou de 21,30 a 22,10% sem diferença significativa. O índice de extensão da proteólise aumentou 3% a cada 10 dias. Apenas em um dos lotes (C) no 30º dia o produto apresentou-se impróprio para o consumo com 1,7 x 10(4) NMP.g-1 de E. coli.

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INTRODUÇÃO: Há pouca informação acerca do nível de qualidade de vida (QV) entre pacientes em hemodiálise (HD) não-elegíveis para transplante renal. OBJETIVO: Foi comparado o nível de QV entre pacientes em HD inscritos e não-inscritos na lista de espera para transplante renal. MÉTODOS: Foram incluídos 161 pacientes portadores de doença renal crônica terminal, mantidos em HD durante abril de 2009, com mais de 18 anos, mais de três meses em HD e sem realização de transplante prévio. Para medida de QV, utilizou-se o SF-36. Também foram coletados dados sobre óbito e transplante ocorridos nos 12 meses seguintes a abril de 2009. As pontuações de QV foram comparadas pela análise de variância com covariáveis. RESULTADOS: Pacientes que não aguardavam transplante eram mais velhos (53,7 versus 36,3 anos; p < 0,001), tinham mais diabetes (15,8 versus 4,7%; p = 0,032) e hipertensão (35,5 versus 12,9%; p < 0,001) e não apresentavam lúpus (0 versus 4,7%; p = 0,001). Esses pacientes também apresentavam creatinina mais baixa (11,5 versus 13,5 mg/dL; p = 0,001) e eram submetidos a menor dose de diálise, estimada pelo Kt/V (1,6 versus 2,0; p = 0,026). Pacientes que não aguardavam transplante evoluíram mais frequentemente para óbito no período de 12 meses (21,1 versus 5,9%; p = 0,005). As médias ajustadas das pontuações foram mais baixas entre os pacientes que não aguardavam transplante em seis dimensões da QV: capacidade funcional (42,0 versus 53,4; p = 0,022); limitação por aspectos físicos (29,9 versus 49,2; p = 0,030); dor (45,0 versus 64,0; p = 0,003); aspectos sociais (56,3 versus 75,9; p = 0,003); limitação por aspectos emocionais (45,1 versus 79,0; p = 0,001) e saúde mental (50,1 versus 64,3; p = 0,004). CONCLUSÕES: Pacientes em HD que não aguardam transplante estão em risco de vivenciar baixa QV, principalmente no que se refere à limitação por aspectos emocionais e físicos. Recomenda-se suporte psicológico e reabilitação física para este grupo de pacientes.

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INTRODUÇÃO: Pacientes com doença renal crônica (DRC) apresentam sinergismo entre fatores de risco tradicionais para aterosclerose e emergentes derivados do estado urêmico. OBJETIVO: Traçar o perfil epidemiológico de um grupo de pacientes com DRC submetido à avaliação cardiológica. MÉTODOS: Pacientes sintomáticos - com isquemia em cintilografia miocárdica e/ou disfunção sistólica ao ecodopplercardiograma - com idade maior que 50 anos e diabetes mellitus (DM) como causa da DRC e aqueles com dois ou mais fatores de risco ateroscleróticos realizaram cineangiocoronariografia. Assintomáticos - não diabéticos e sem fatores de risco - foram investigados com ecodopplercardiograma e aqueles com único fator de risco, por meio de ecodopplercardiograma e cintilografia. RESULTADOS: Foram estudados 46 pacientes, 58,7% homens, idade de 50-70 ± 11,7 anos, 91,3% dialíticos. Tempo de hemodiálise: 61,96 ± 55,1 meses. Hipertensão arterial foi causa da DRC em 56,5%. Dos 28 pacientes (60,9%) submetidos à cineangiocoronariografia, 53,6% apresentaram doença arterial coronariana (DAC). Os pacientes foram divididos em três grupos: com DAC (A), sem DAC (B) e não submetidos à cineangiocoronariografia (C). Diferença significativa ocorreu entre os Grupos B e C na frequência de índice tibiobraquial (ITB) anormal (p = 0,026), com ausência de ITB anormal no Grupo C e na média de idade, superior no B (p = 0,045). No Grupo A, 53,3% dos pacientes estavam em avaliação pré-paratireoidectomia (PTX). CONCLUSÃO: Este estudo confirmou a alta frequência de alterações cardiovasculares, inclusive de DAC, nos pacientes portadores de DRC, principalmente naqueles em diálise.