AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients / O acúmulo de AGEs está relacionado à degeneração muscular e calcificação vascular em pacientes em diálise peritoneal

Abstract Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Resumo Histórico: Pacientes com doença renal crônica (DRC) são afetados pela dinapenia, sarcopenia e calcificação vascular. Produtos finais da glicação avançada (AGEs) podem se acumular em pacientes em diálise peritoneal (DP) e favorecer a sarcopenia por meio de alterações em ligações cruzadas do colágeno, quebra da proteína muscular e calcificação das células do músculo liso arterial por meio da ativação da p38-MAPK. O objetivo deste estudo é explorar as relações entre AGEs, degeneração muscular e calcificação da artéria coronária. Métodos: Este foi um estudo clínico observacional em pacientes com DRC submetidos à DP, no qual foram medidos os AGEs séricos e teciduais (AGEs-sAF), a carga cumulativa de glicose, a força muscular e testes funcionais, ultrassonografias musculares com elastografia, quantificação do cálcio da artéria coronária (CAC), e a densidade muscular por tomografia computadorizada multislice. Resultados: 27 pacientes com idade entre 48±16 anos, tempo de diálise entre 27±17 meses, tinham níveis de AGEs-sAF de 3,09±0,65 UA (elevado em 13 [87%] pacientes), níveis de força de preensão de 26,2±9,2 kg (11 [42%] pacientes com dinapenia), velocidade de marcha de 1,04±0,3 m/s (anormal em 14 [58%] pacientes) e teste "timed-up-and-go" (TUG) de 10,5±2,2s (anormal em 7 [26%] pacientes). Foram detectadas correlações entre os níveis AGEs-sAF e a elastografia do reto femoral (R=-0,74; p=0,02), a elastografia tibial anterior (R= -0,68; p=0,04) e a CAC (R=0,64; p=0,04). A carga cumulativa de glicose se correlacionou com a elastografia do reto femoral (R=-0,6; p=0,02), as concentrações séricas de hemoglobina glicada se correlacionaram com a densidade muscular do psoas (R= -0,58; p=0,04) e o CAC se correlacionou com a densidade do músculo psoas (R=-0,57; p=0,01) e a densidade do músculo quadrado lombar (R=-0,63; p=0,005). Conclusões: O estudo revelou associações entre o acúmulo de AGEs e menor rigidez/densidade muscular. Foram observadas associações que ligavam parâmetros de degeneração muscular com a calcificação vascular.

Cirurgia bariátrica e o escore de cálcio coronariano / Bariatric surgery and the coronary artery calcium score

RESUMO Objetivo: investigar o impacto da cirurgia bariátrica no escore de cálcio coronariano (ECC) e estabelecer fatores preditivos de progressão desse escore em pacientes obesos. Métodos: estudo prospectivo de 18 pacientes obesos antes e depois da cirurgia bariátrica. Todos os pacientes foram submetidos à tomografia computadorizada e a exames laboratoriais com dosagens sanguíneas de colesterol total, LDL, HDL, triglicerídeos, glicose de jejum, A1C, insulina, cálcio sérico, peptídeo C e proteína C-reativa, para determinar o ECC e o escore de risco de Framingham (ERF). Resultados: o ERF reduziu 50% entre as avaliações pré e pós-operatórias. O ECC médio aumentou significativamente no período pós-operatório, aumentando de 8,5 para 33,1. Os níveis de HDL também aumentaram no pós-operatório. Todas as outras variáveis quantitativas reduziram significativamente no pós-operatório. Ao estratificar o ECC em quatro categorias, foi observado que 22,2% da amostra apresentou ECC=0 no pós-operatório. A prevalência de ECC leve reduziu de 77,8% para 50%, enquanto que ECC moderado permaneceu igual no pré e no pós-operatório (11,1%). ECC grave aumentou de 11,1% para 16,7%. Idade avançada foi associada à progressão do ECC, e essa foi a única variável que apresentou correlação estatística com a progressão do ECC. Conclusão: cirurgia bariátrica produz desfechos cardiovasculares positivos, que, aparentemente, ocorrem de forma independente do ECC.

ABSTRACT Objective: to investigate the impact of bariatric surgery on the coronary artery calcium score (CACS), and to establish predictors of progression of this score in patients with obesity. Methods: prospective study that evaluated 18 obese patients before and after bariatric surgery. All patients were submitted to computed tomography scans and blood tests (total cholesterol, LDL, HDL, triglycerides, fasting plasma glucose, A1C, insulin, serum calcium, C-peptide and C-Reactive Protein) in order to determine CACS and Framingham risk score (FRS). Results: the FRS decreased 50% between the pre and postoperative evaluations. The mean CACS increased significantly at the late postoperative period, going from 8.5 to 33.1. HDL levels had also increased between the pre and postoperative periods. All of the other quantitative variables reduced significantly at the postoperative evaluation. When dividing CACS into four degrees, it was observed that 22.2% presented CACS=0 at the postoperative evaluation. The prevalence of mild CACS decreased from 77.8% to 50%, while moderate CACS remained the same (11.1%). Severe CACS increased from 11.1% to 16.7%. Older ages were linked to CACS progression, and this was the only variable that presented statistical association with progression. Conclusion: bariatric surgery leads to positive cardiovascular outcomes, apparently regardless of CACS.

Prevalencia y extensión de la calcificación arterial coronaria en población mexicana asintomática cardiovascular: estudio Genética de la Enfermedad Aterosclerosa / Prevalence and extent of coronary artery calcification in an asymptomatic cardiovascular Mexican population: Genetics of Atherosclerotic Disease study

Resumen: Objetivo: La prevalencia de calcificación arterial coronaria (CAC), marcador específico de aterosclerosis, no es conocida en México. Nuestro objetivo fue investigar la prevalencia y extensión de CAC y su asociación con factores de riesgo cardiovascular en población mexicana. Métodos: La CAC fue medida por tomografía computarizada multidetector en individuos asintomáticos que participaron en el estudio Genética de la Enfermedad Aterosclerosa. Los factores de riesgo cardiovascular y los medicamentos fueron registrados. Resultados: La muestra incluyó 1,423 individuos (49.5% hombres), con una edad de 53.7 ± 8.4 años. Los portadores de CAC mostraron prevalencias más altas de dislipidemia, diabetes, hipertensión y otros factores de riesgo. La prevalencia de CAC > 0 unidades Agatston fue de 27%, significativamente más alta en hombres (40%) que en mujeres (13%). Los valores medios del puntaje de CAC aumentaron consistentemente con la edad y fueron más altos en hombres que en mujeres en todos los grupos etarios. La edad y el c-LDL elevado se asociaron de manera independiente con la prevalencia de CAC > 0 en hombres y mujeres, mientras que la presión arterial sistólica en las mujeres, y el incremento de la edad en ambos géneros mostró una asociación independiente con la severidad de CAC. Conclusiones: En población mexicana la prevalencia y la extensión de CAC fueron mucho más altas en hombres que en mujeres y aumentaron consistentemente con la edad. Los predictores independientes de la prevalencia de CAC fueron la edad y el c-LDL.

Abstract: Objective: The prevalence of coronary artery calcification (CAC), a specific marker of atherosclerosis, is unknown in Mexico. Our aim was to investigate the prevalence and quantity of CAC and their association with cardiovascular risk factors in a Mexican population. Methods: CAC was measured by multidetector computed tomography in asymptomatic subjects who participated in the Genetics of Atherosclerotic Disease study. Cardiovascular risk factors and medication were recorded. Results: The sample included 1,423 individuals (49.5% men), aged 53.7 ± 8.4 years. Those with CAC showed a higher prevalence of dyslipidaemia, diabetes, hypertension, and other risk factors. The prevalence of CAC > 0 Agatston units was significantly higher among men (40%) than among women (13%). Mean values of CAC score increased consistently with increasing age and were higher in men than women in each age group. Age and high low density lipoprotein cholesterol were independently associated with prevalence of CAC > 0 in men and women, while increasing systolic blood pressure in women and age in both genders showed an independent association with CAC extension. Conclusions: In the Mexican population the prevalence and extent of CAC were much higher in men than in women, and strongly increased with age. Independent predictors of CAC prevalence were age and low density lipoprotein cholesterol (LDL-C).

Prevalence of factors related to vascular calcification in patients with chronic kidney disease on dialysis

The main aim of the study was to determine the prevalence of vascular calcifications in patients with chronic kidney disease on dialysis in our population assessed by X-ray. The secondary objectives were to determine the cardiovascular risk factors associated with the presence of vascular calcifications and to evaluate the complementary use of the echocardiogram in a cross-sectional, observational, multicentric study. We included patients with chronic kidney disease on dialysis, age =18 years with at least 3 months of renal replacement therapy in 8 dialysis centres in Argentina. The degree of vascular calcification was determined using Adragao and Kauppila scores. The presence of valvular calcifications was established through a trans-thoracic doppler echocardiogram. Univariate and multivariate analysis were undertaken, considering the degree of vascular calcification as the dependent variable; 443 adult patients were evaluated at 8 centres across 5 provinces in Argentina. The prevalence of vascular calcifications by the X-rays was 63%, while 73% presented calcifications in hands and pelvis, with an Adragao score >3, and 60% presented calcifications in the abdominal aorta with a Kauppila score >4. The prevalence of valvular calcifications: 28%. We have shown a higher rate of vascular calcifications with the use of plain X-rays when compared to the prevalence of valvular calcifications obtained with echocardiograms. In this regard, valvular calcifications were present particularly in those patients with a severe level of radiological vascular calcification.

El objetivo primario del estudio fue determinar la prevalencia de calcificaciones vasculares en pacientes con enfermedad renal crónica (ERC) en diálisis, a través de métodos accesibles y reproducibles. Como objetivo secundario: determinar los factores de riesgo cardiovascular asociados a la presencia de calcificaciones vasculares y evaluar la utilidad complementaria del ecocardiograma. Fue un estudio prospectivo, transversal y multicéntrico sobre pacientes prevalentes con ERC en diálisis. Se les realizaron radiografía de columna lumbar, de manos y panorámica de pelvis, para la determinación de las escalas de Adragao y Kauppila. La presencia de calcificaciones valvulares fue establecida por ecocardiograma doppler color transtorácico. Se obtuvieron los datos de 30 variables determinadas para el análisis uni y multivariado (regresión logística) de los factores de riesgo asociados. Se evaluaron 443 pacientes adultos de 8 centros de 5 provincias de la Argentina. La prevalencia de calcificaciones vasculares, determinada por las radiografías, fue 63%. La prevalencia de calcificaciones valvulares fue 28%. Las calcificaciones valvulares estuvieron presentes en aquellos pacientes con graves calcificaciones radiológicas. Las calcificaciones estuvieron asociadas a la edad (>55 años), sexo masculino, diabetes, tiempo de diálisis, tabaquismo y la presencia de enfermedad vascular periférica. Este es el estudio con mayor número de pacientes evaluados en Latinoamérica. Se encuentra alta prevalencia de calcificaciones vasculares en Argentina, fácilmente medibles con técnicas no invasivas como la radiografía simple, que resulta más sensible que el ecocardiograma. Ambos estudios deben ser utilizados de manera complementaria.

Prevalence of suggestive images of carotid artery calcifications on panoramic radiographs and its relationship with predisposing factors / Prevalência de imagens sugestivas de calcificações da artéria carótida em radiografias panorâmicas e sua relação com fatores predisponentes

Abstract Panoramic radiographs (PR) can display radiopaque images suggestive of calcified atheroma in the carotid artery in asymptomatic patients. The aim of this study was to evaluate the prevalence of these images on PR and their linkage with hypertension, obesity, age, gender and smoking habits. PR of 505 patients were evaluated. They were older than 30 years old and their PR had been taken for different clinical reasons. Their body mass index was calculated; their waist circumference was also taken into consideration. Information about smoking habits and hypertension was obtained. The observers analyzed the presence of radiopaque mass in the region of the cervical vertebrae C3-C4 through the PR, confirmed by an antero-posterior (AP) radiograph. The results showed a 7.92% prevalence of suggestive images of calcifications on PR and on AP radiograph. The adjusted Odds Ratio showed association with age and smoking habits. The calcification process is almost nine times higher for the elderly when compared to the young. As far as smokers are concerned, this process is twice worse when compared to no smokers. In conclusion, 7.92% of the group studied presented suggestive images of carotid atherosclerosis on PR, which is directly associated with the age and smoking habits.

Resumo As radiografias panorâmicas (RP) podem exibir imagens radiopacas sugestivas de ateromas calcificados na artéria carótida em pacientes assintomáticos. O objetivo deste estudo foi avaliar a prevalência destas imagens na RP e sua relação com hipertensão, obesidade, idade, sexo e tabagismo. Foram avaliadas RP de 505 pacientes acima de trinta anos, que realizaram esse exame por diversos motivos clínicos. Seu índice de massa corpórea foi calculado; sua circunferência abdominal também foi considerada. Informações sobre hipertensão e tabagismo foram obtidas. Os observadores avaliaram as RP para a presença de massas radiopacas na região das vértebras cervicais C3-C4, confirmadas por meio de uma radiografia ântero-posterior (AP). Os resultados mostraram prevalência de 7,92% de imagens sugestivas de calcificações em RP e na radiografia AP. A razão de probabilidade (OR) ajustada mostrou associação com idade e tabagismo. O risco para as pessoas mais velhas aumenta até cerca de nove vezes quando comparado com aqueles mais jovens, enquanto para os fumantes, o risco é o dobro, quando comparado com não fumantes. Na população estudada, 7,92% de todos os sujeitos apresentaram imagens sugestivas de aterosclerose carotídea em RP e houve associação com idade e tabagismo.

Distúrbio mineral ósseo e calcificação vascular em pacientes renais crônicos / Mineral and bone disorder and vascular calcification in patients with chronic kidney disease

Calcificações vasculares têm sido associadas aos distúrbios minerais e ósseos. As alterações nas concentrações séricas de cálcio e fosfato são fatores importantes implicados no processo da calcificação arterial na doença renal crônica. A patogênese da calcificação vascular é um mecanismo complexo e não completamente claro, podendo corresponder a um processo ativo de transformação celular e ossificação heterotópica. Além da hipercalcemia e hiperfosfatemia, estão envolvidos neste processo alterações no metabolismo de substâncias inibidoras e promotoras de calcificação como a fetuína A, osteopontina, osteoprotegerina e proteína de matriz gla. Para o diagnóstico da lesão arterial calcificada, estão disponíveis diversos métodos, um método de estimativa do risco cardiovascular baseado em radiografias simples de coluna lombar e outro método baseado em radiografias simples da pelve e das mãos. Apresentamos, a seguir, uma revisão abordando a relação entre calcificações vasculares e os distúrbios minerais.

Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders.

The association of breast arterial calcification and metabolic syndrome

OBJECTIVES: We investigated the relationship between metabolic syndrome and breast arterial calcification detected via mammography in a cohort of postmenopausal subjects. METHODS: Among 837 patients referred to our radiology department for mammographic screening, 310 postmenopausal females (105 patients with and 205 patients without breast arterial calcification) aged 40 to 73 (mean 55.9±8.4) years were included in this study. The groups were compared with respect to clinical characteristics and metabolic syndrome criteria. Univariate and multivariate analyses identified the factors related to breast arterial calcification. RESULTS: Age, postmenopausal duration and the frequencies of diabetes mellitus, hypertension and metabolic syndrome were significantly higher in the subjects with breast arterial calcification than in those without (p<0.05). Multivariate analysis indicated that age (OR = 1.3, 95% CI = 1.1-1.6, p = 0.001) and metabolic syndrome (OR = 4.0, 95% CI = 1.5−10.4, p = 0.005) were independent predictors of breast arterial calcification detected via mammography. The independent predictors among the features of metabolic syndrome were low levels of high-density lipoproteins (OR = 8.1, 95% ...

The occurrence of dental caries is associated with atherosclerosis

OBJECTIVE: Previous studies have suggested that marginal periodontitis is a risk factor for developing atherosclerosis. The objective of this study was to determine whether caries may also be associated with atherosclerosis. METHODS: The computed tomography data sets of 292 consecutive patients, 137 women and 155 men with a mean age of 54.1±17.3 years, were analyzed. Caries were quantified based on the number of decayed surfaces of all the teeth, and periodontitis was quantified on the basis of the horizontal bone loss in the jaw. The presence of chronic apical periodontitis (CAP) was assessed, and the aortic atherosclerotic burden was quantified using a calcium scoring method. RESULTS: The patients with <1 caries surfaces/tooth had a lower atherosclerotic burden (0.13±0.61 mL) than patients with ≥1 caries surfaces/tooth. The atherosclerotic burden was greater in patients with a higher number of lesions with pulpal involvement and more teeth with chronic apical periodontitis. In the logistical regression models, age (Wald 49.3), number of caries per tooth (Wald 26.4), periodontitis (Wald 8.6), and male gender (Wald 11) were found to be independent risk factors for atherosclerosis. In the linear regression analyses, age and the number of decayed surfaces per tooth were identified as influencing factors associated with a higher atherosclerotic burden, and the number of restorations per tooth was associated with a lower atherosclerotic burden. CONCLUSION: Dental caries, pulpal caries, and chronic apical periodontitis are associated positively, while restorations are associated inversely, with aortic atherosclerotic burden. Prospective studies are required to confirm these observations and answer the question of possible causality. .

Formas graves de retinopatia predizem aterosclerose subclínica em indivíduos com diabetes tipo 1 / Severe forms of retinopathy predict the presence of subclinical atherosclerosis in type 1 diabetes subjects

FUNDAMENTO: Em pacientes com diabetes tipo 2, a presença de retinopatia está associada a doença cardiovascular aumentada, independentemente dos fatores de risco conhecidos para a doença vascular. OBJETIVO: Investigar a associação da retinopatia diabética (RD) e seus graus com a presença de aterosclerose coronariana subclínica em pacientes com diabetes tipo 1. MÉTODOS: Um estudo transversal foi conduzido com 150 pacientes com diabetes tipo 1, assintomáticos para doença arterial coronariana. Foram submetidos à avaliação clínica para verificar complicações microvasculares e avaliação para a presença de calcificação arterial coronariana (CAC). RESULTADOS: Formas graves de RD (RD grave não proliferativa - RDNP - e RD proliferativa - RDP) foram associadas à CAC (RC: 3,98; IC de 95 por cento; 1,13-13,9, p = 0,03), de maneira independente dos fatores de risco conhecidos para a doença cardiovascular (idade, A1C, hipertensão, dislipidemia e sexo masculino). CONCLUSÃO: Os pacientes com formas graves de RD estão em risco de presença de doença arterial coronariana, de maneira independente dos tradicionais fatores de risco cardiovascular.

BACKGROUND: In patients with type 2 diabetes, the presence of retinopathy is associated with increased cardiovascular disease, regardless of known risk factors for vascular disease. OBJECTIVE: To investigate the association of diabetic retinopathy (DR) and its grades with the presence of subclinical coronary atherosclerosis in patients with type 1 diabetes. METHODS: A cross-sectional study was conducted with 150 type 1 diabetes individuals asymptomatic for coronary artery disease. They underwent clinical evaluation for microvascular complications and for the presence of coronary artery calcification (CAC). RESULTS: Severe forms of DR (severe non-proliferative DR and proliferative DR) were associated with CAC (OR: 3.98 95 percent CI 1.13-13.9, p = 0.03), regardless of known risk factors for cardiovascular disease (age, A1C, hypertension, dyslipidemia and male gender). CONCLUSION: Patients with severe forms of DR are at risk for the presence of coronary artery disease regardless of traditional cardiovascular risk factors.