RESUMEN
Over 200 million individuals worldwide are estimated to have peripheral artery disease (PAD). Although the term peripheral can refer to any outer branch of the vasculature, the focus of this review is on lower-extremity arteries. The initial sequelae of PAD often include movement-induced cramping pain in the hips and legs or loss of hair and thinning of the skin on the lower limbs. PAD progresses, sometimes rapidly, to cause nonhealing ulcers and critical limb ischemia which adversely affects mobility and muscle tone; acute limb ischemia is a medical emergency. PAD causes great pain and a high risk of amputation and ultimately puts patients at significant risk for major adverse cardiovascular events. The negative impact on patients' quality of life, as well as the medical costs incurred, are huge. Atherosclerotic plaques are one cause of PAD; however, emerging clinical data now shows that nonatherosclerotic medial arterial calcification (MAC) is an equal and distinct contributor. This ATVB In Focus article will present the recent clinical findings on the prevalence and impact of MAC in PAD, discuss the known pathways that contribute specifically to MAC in the lower extremity, and highlight gaps in knowledge and tools that limit our understanding of MAC pathogenesis.
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Enfermedad Arterial Periférica/etiología , Calcificación Vascular/complicaciones , Factores de Edad , Isquemia Crónica que Amenaza las Extremidades/etiología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Extremidad Inferior/irrigación sanguínea , Modelos Cardiovasculares , Enfermedad Arterial Periférica/patología , Placa Aterosclerótica/complicaciones , Calidad de Vida , Túnica Media/patología , Calcificación Vascular/genética , Calcificación Vascular/patologíaRESUMEN
OBJECTIVE: The present study evaluated the effect of endovascular administration of calcium chloride to the carotid artery of swines, to create a model of arterial calcification. METHODS: Fifteen Large White pigs were used for the study. Via endovascular treatment, carotid arteries were exposed during 9 min to either calcium chloride (experimental artery) or saline (control artery) with the use of the TAPAS catheter. Intravascular ultrasound (IVUS) imaging was obtained at baseline, postprocedure and at 30 days. Optical coherence tomography (OCT) imaging was obtained in vitro after carotids were harvested. Longitudinally cut parallel arterial segments were placed in a system of delicate clamps and underwent uniaxial strain test. All arteries underwent histopathological examination. RESULTS: Calcium chloride treated segments showed extensive circumferential parietal calcification evident on both IVUS and OCT. Reduction in minimal lumen area on IVUS was evident in experimental arteries both at 24 hr and 30 days postprocedure. Histopathologic assessment (Von Kossa stain) confirmed medial calcification with mild intimal thickening. Biomechanical testing showed treated segments to have smaller breaking strength and less elastic deformation than controls. CONCLUSION: We developed a nonexpensive, reproducible model of early carotid medial calcification in pigs. Our model has the potential to help the development of research to unravel mechanisms underlying arterial calcification, the use of current or new devices to treat calcified lesions as well as to serve as an option for training interventionalists on the use of such devices.
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Cloruro de Calcio , Enfermedades de las Arterias Carótidas/inducido químicamente , Arteria Carótida Común/patología , Calcificación Vascular/inducido químicamente , Animales , Fenómenos Biomecánicos , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/diagnóstico por imagen , Modelos Animales de Enfermedad , Elasticidad , Masculino , Neointima , Sus scrofa , Factores de Tiempo , Tomografía de Coherencia Óptica , Ultrasonografía Intervencional , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patologíaRESUMEN
BACKGROUND: Although elevated high-density lipoprotein cholesterol (HDL-C) is considered protective against atherosclerotic cardiovascular disease, no causal relationship has been demonstrated. HDL-C comprises a group of different subfractions that might have different effects on atherosclerosis. Our objective was to investigate the association between HDL-C subfractions with the coronary artery calcium (CAC) score. METHODS: We included 3,674 (49.8 ± 8.3 years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD and were not currently using lipid-lowering medications. We measured the fasting lipoprotein cholesterol fractions (in mmol/l) by a zonal ultracentrifugation method (VAP). We analyzed the independent predictive values of total HDL-C, HDL2-C, and HDL3-C subfractions and in the HDL2-C/HDL3-C ratio using linear regression to predict Ln(CAC+1) and logistic regression to predict the presence of CAC. RESULTS: Overall 912 (24.8%) of the participants had CAC>0, and 294 (7.7%) had CAC>100. The mean total HDL-C, HDL2-C, and HDL3-C were: 1.42 ± 0.37, 0.38 ± 0.17 and 1.03 ± 0.21 mmol/l, respectively. Individuals with CAC>0 had lower levels of total HDL-C as well as of each subfraction (p < 0.001). When adjusted for age, gender, smoking, hypertension, alcohol use, physical activity, and LDL-C, we observed an inverse association between HDL-C and its subfractions and CAC (p < 0.05). However, by adding triglycerides in the adjustment, neither total HDL-C nor its subfractions remained independently associated with the presence or extent of CAC. CONCLUSION: In this cross-sectional analysis, neither the total HDL-C nor its subfractions (HDL2-C and HDL3-C, as well as HDL2-C/HDL3-C ratio) measured by VAP are independently associated with the presence or extent of coronary calcification.
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Aterosclerosis/patología , Calcio/análisis , HDL-Colesterol/sangre , Colesterol/sangre , Vasos Coronarios/patología , Lipoproteínas/sangre , Calcificación Vascular/patología , Adulto , Aterosclerosis/sangre , Brasil , Estudios Transversales , Ayuno , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
ABSTRACT Introduction: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. Methods: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. Results: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. Conclusion: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.
RESUMO Introdução: Existem evidências de que a aldosterona exerça um papel na patogênese da calcificação vascular. O objetivo deste estudo foi avaliar o efeito da espironolactona, um antagonista do receptor mineralocorticoide, na progressão da calcificação coronariana (CC) de pacientes em diálise peritoneal, e identificar os fatores envolvidos nessa progressão. Métodos: Trinta e três pacientes com escore de cálcio coronariano (ECC) ≥ 30, detectado por tomografia computadorizada com múltiplos detectores (TCMD) e expresso em unidades de Agatston, foram randomizados para um grupo que recebeu 25 mg de espironolactona por dia durante 12 meses (grupo espironolactona) e um grupo controle que não recebeu este medicamento. O desfecho primário foi a mudança percentual do ECC do início para o final do estudo (progressão relativa), quando uma nova TCMD foi realizada. Os pacientes que tiveram progressão de CC foram comparados com aqueles que não progrediram. Resultados: Dezesseis pacientes, sete no grupo espironolactona e nove no grupo controle, concluíram o estudo. A progressão relativa do ECC foi semelhante nos dois grupos, 17,2% e 27,5% nos grupos espironolactona e controle, respectivamente. Cinquenta e sete por cento dos pacientes tratados e 67% daqueles no grupo controle apresentaram progressão nos escores de CC (p = 0,697). Os pacientes progressores diferiram dos não progressores porque apresentaram níveis séricos mais elevados de cálcio e LDL-colesterol e menores níveis de albumina. Conclusão: Em pacientes em diálise peritoneal, a espironolactona não atenuou a progressão da CC. No entanto, estudos em grande escala são necessários para confirmar essa observação. Distúrbios do metabolismo mineral e dislipidemia estão envolvidos na progressão da CC.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Espironolactona/uso terapéutico , Diálisis Peritoneal , Progresión de la Enfermedad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/sangre , Espironolactona/administración & dosificación , Tomógrafos Computarizados por Rayos X , Proyectos Piloto , Calcio/sangre , Estudios Prospectivos , Estudios de Seguimiento , Resultado del Tratamiento , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Insuficiencia Renal Crónica/terapia , Perdida de Seguimiento , Calcificación Vascular/patología , Calcificación Vascular/diagnóstico por imagen , Albúmina Sérica Humana/análisis , LDL-Colesterol/sangreRESUMEN
INTRODUCTION: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. METHODS: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. RESULTS: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. CONCLUSION: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.
Asunto(s)
Progresión de la Enfermedad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Diálisis Peritoneal , Espironolactona/uso terapéutico , Calcificación Vascular/sangre , Calcificación Vascular/tratamiento farmacológico , Anciano , Calcio/sangre , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Humanos , Perdida de Seguimiento , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Proyectos Piloto , Estudios Prospectivos , Insuficiencia Renal Crónica/terapia , Albúmina Sérica Humana/análisis , Espironolactona/administración & dosificación , Tomógrafos Computarizados por Rayos X , Resultado del Tratamiento , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patologíaRESUMEN
OBJECTIVES: This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. BACKGROUND: Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. METHODS: We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications. RESULTS: Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features were lower in lesions in statin-taking patients (0.49 ± 2.39% per year vs. 1.06 ± 2.42% per year and 0.9% per year vs. 1.6% per year, respectively; all p < 0.001). The rates of progression to >50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. CONCLUSIONS: Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).
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Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Vasos Coronarios/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Placa Aterosclerótica , Anciano , Brasil , Angiografía por Tomografía Computarizada , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Progresión de la Enfermedad , Europa (Continente) , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Persona de Mediana Edad , América del Norte , Estudios Prospectivos , Sistema de Registros , República de Corea , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patologíaRESUMEN
Vascular calcification is a tightly regulated process that increases during ageing and occurs mainly in patients with diabetes and chronic renal failure. Exosomes are small membrane vesicles that are synthesized in a particular population of endosomes, also called multivesicular bodies, by inside budding into the lumen of the compartment. After fusion of exosome with the plasma membrane, these internal vesicles are secreted. Exosomes have a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate. Investigators implicated microvesicles/exosomes as a specific signaling mechanism to induce vascular mineralization during vascular smooth muscle cells phenotypic transition. Vascular wall from healthy individual exhibit exosomes loaded with calcification inhibitors such as Fetuin A and MGP. Conversely, calcifying conditions induce secretion of exosomes, characterized by decreased calcifying inhibitors and increased phosphatidyl serine and Annexin A6 content, which serves as a nidus for vascular calcification.
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Señalización del Calcio , Calcio/metabolismo , Exosomas/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/metabolismo , Animales , Arterias/metabolismo , Arterias/patología , Exosomas/patología , Humanos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Calcificación Vascular/patologíaRESUMEN
BACKGROUND AND AIMS: Obesity and diabetes potentiate vascular calcification by increasing vascular smooth muscle cells osteoblastic differentiation mediated by the transcription factor Msx2 and bone morphogenetic protein-2 signaling. However, Bmp-2/Msx2 crosstalk to induce VSMC osteogenic phenotype transition and calcification is poorly understood in diabetes. We aimed to investigate mechanisms underlying Bmp-2-driven VSMC osteogenic differentiation and calcification in leptin-deficient ob/ob mice. METHODS: We incubated VSMC from ob/ob mice and wild type C57BL/6 littermates with or without Bmp-2. We used loss-of-function experiments to investigate the role of Msx2 in Bmp-2-induced ob/ob VSMC osteochondrogenic differentiation and calcification by transfecting Msx2 siRNA into VSMC. RESULTS: Baseline ob/ob VSMC and aorta showed increased Msx2, Runx2, alkaline phosphatase mRNA and protein expression, which further increased in Bmp-2-incubated ob/ob VSMC, therefore augmenting ob/ob VSMC calcification in comparison to wild type VSMC. Accordingly, signaling pathways to induce VSMC osteogenic differentiation, such as Smad1/5 phosphorylation increased in ob/ob versus wild type aorta. In comparison to wild type VSMC, Msx2 siRNA transfected VSMC decreased Bmp-2-dependent osteochondrogenic differentiation response by abrogating Msx2, Runx2, Alpl expression in ob/ob but not in wild type VSMC. Nonetheless, Msx2 inhibition did not decrease calcification in Bmp-2 stimulated ob/ob VSMC in vitro. CONCLUSIONS: Our data support a crucial role of Msx2 for ob/ob VSMC osteochondrogenic differentiation, however, Msx2 signaling alone is not sufficient for ob/ob VSMC calcification after Bmp-2 stimulation in vitro. These findings can be translated into novel perspectives for the understanding of the mechanisms and to provide therapeutic targets underlying vascular calcification in type 2 diabetes.
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Enfermedades de la Aorta/metabolismo , Proteínas de Homeodominio/metabolismo , Resistencia a la Insulina , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Obesidad/metabolismo , Osteoblastos/metabolismo , Osteogénesis , Calcificación Vascular/metabolismo , Animales , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Proteína Morfogenética Ósea 2/deficiencia , Proteína Morfogenética Ósea 2/genética , Células Cultivadas , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Resistencia a la Insulina/genética , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Obesidad/genética , Obesidad/patología , Osteoblastos/patología , Fenotipo , Interferencia de ARN , Transducción de Señal , Transfección , Calcificación Vascular/genética , Calcificación Vascular/patologíaRESUMEN
Parathyroidectomy (PTX) may cause low levels of PTH, leading to an excessive reduction of bone turnover, which is associated with poor outcomes in dialysis patients, including vascular calcification (VC). We aimed to prospectively investigate the impact of PTX on bone remodeling and its potential consequence on the progression of VC in hemodialysis patients. In this prospective study, 19 hemodialysis patients with severe secondary hyperparathyroidism (sHPT) were evaluated. All patients underwent laboratorial tests and coronary tomography at baseline and, 6 and 12 months after PTX; bone biopsy was performed at baseline and 12-month. At baseline, all patients had increased PTH levels up to 2500 pg/mL and high turnover bone disease in their bone biopsies. Fourteen (74%) patients had VC. During the follow-up, there was a significant decrease of PTH at 6 and 12-month. At 12-month, 90% of the patients evolved to low turnover bone disease. During the period of the hungry bone syndrome (first 6 months), no change of coronary calcium score was observed. However, calcium score increased significantly thereafter (12th month). There was an association between VC progression and the severity of low turnover bone disease. In conclusion, the shift from high to low turnover bone disease after PTX occurs in parallel to VC progression, contributing to the understanding of the complex pathophysiology involving mineral metabolism and cardiovascular disease in hemodialysis patients.
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Remodelación Ósea , Paratiroidectomía , Diálisis Renal , Calcificación Vascular/patología , Adulto , Biopsia , Huesos/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVES: We sought to assess a new modality of radiofrequency intravascular ultrasound (IVUS) called iMAP-IVUS (Boston Scientific, Santa Clara, California) during the evaluation of patients presenting with high-risk acute coronary syndromes. BACKGROUND: There are limited data on plaque tissue characterization and phenotype classification using iMAP-IVUS. METHODS: In the iWonder study patients presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI underwent three-vessel grayscale IVUS and iMAP-IVUS tissue characterization prior to percutaneous intervention. In total 385 lesions from 100 patients were divided into culprit (n = 100) and nonculprit (n = 285) lesions. Lesion phenotype was classified as (i) thin-cap fibroatheroma (iMAP-derived TCFA); (ii) thick-cap fibroatheroma; (iii) pathological intimal thickening; (iv) fibrotic plaque; and (v) fibrocalcific plaque. RESULTS: Culprit lesions had smaller minimum lumen cross-sectional area (MLA) with greater plaque burden compared to non-culprit lesions. Volumetric analysis showed that culprit lesions had longer length and larger vessel and plaque volumes compared to non-culprit lesions. iMAP-IVUS revealed that culprit lesions presented more NC and fibrofatty volume, both at lesion level and at the MLA site (all P < 0.001). Any fibroatheroma was more frequently identified in culprit lesions compared with non-culprit lesions (93% vs. 78.9%, P = 0.001), anywhere within the lesion 19.0%, P < 0.001) as well as at the MLA site (18.0% vs. 9.5%, P = 0.07). CONCLUSIONS: Three-vessel radiofrequency iMAP-IVUS demonstrated a greater plaque burden and higher prevalence of any fibroatheroma as well as iMAP-derived TCFAs in culprit versus non-culprit lesions in patients presenting with STEMI or non-STEMI undergoing percutaneous coronary intervention. © 2017 Wiley Periodicals, Inc.
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Síndrome Coronario Agudo/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Placa Aterosclerótica , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Síndrome Coronario Agudo/patología , Síndrome Coronario Agudo/terapia , Anciano , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/patología , Femenino , Fibrosis , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/patología , Infarto del Miocardio sin Elevación del ST/terapia , Intervención Coronaria Percutánea , Fenotipo , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Rotura Espontánea , Infarto del Miocardio con Elevación del ST/patología , Índice de Severidad de la Enfermedad , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patologíaRESUMEN
Resumo Contexto O índice tornozelo-braquial (ITB) é um exame de rastreamento da doença arterial obstrutiva periférica, sendo também utilizado para avaliar o risco cardiovascular. Em diabéticos, a interpretação do exame é difícil pela possibilidade de índice aberrante devido à calcificação da camada média arterial. Objetivo Encontrar a frequência de ITB aberrante em diabéticos e verificar sua associação com variáveis sociodemográficas. Métodos Estudo descritivo com entrevista e aferição de ITB de 309 pacientes diabéticos tipo 2, acompanhados no centro de referência Centro de Diabetes e Endocrinologia da Bahia (CEDEBA), Salvador, BA, Brasil. Foi estudada a frequência e a relação entre o ITB aberrante e variáveis sociodemográficas, como sexo, idade e renda familiar. Utilizou-se um ponto de corte para ITB aberrante de 1,3. As variáveis contínuas foram dicotomizadas. Para a análise estatística, utilizou-se o teste do qui-quadrado, considerando significante um p ≤ 0,05. Resultados Entre os 309 pacientes entrevistados, 65% eram mulheres, 26% haviam cursado ensino médio completo e 77% tinham renda familiar igual ou menor que três salários mínimos. A frequência de ITB aberrante ≥ 1,3 foi 16,5%. Não foram encontradas correlações estatisticamente significantes nas análises bivariadas entre o ITB aberrante (≥ 1,3) e as variáveis sociodemográficas estudadas (sexo, idade, tempo de duração de diabetes melito, renda familiar e escolaridade). Conclusões A frequência de ITB aberrante entre diabéticos foi de 16,5%. Não encontramos correlação entre as variáveis sociodemográficas (sexo, idade, tempo de DM, escolaridade e renda familiar) e a ocorrência de ITB aberrante.
Abstract Background The ankle-brachial index (ABI) is a screening test for peripheral arterial occlusive disease and it can also be used to assess cardiovascular risk. However, in diabetics it can be difficult to interpret because the index may be excessively high because of calcification of the arterial tunica media. Objective To determine the frequency of high ABI in diabetics and to test for associations with sociodemographic variables. Methods This was a descriptive study in which 309 type 2 diabetes patients were interviewed and had their ABI measured. The sample was recruited at a referral center for diabetes and endocrinology (CEDEBA) in Salvador, BA, Brazil. The frequency of excessively high ABI and its relationships with sociodemographic variables such as sex, age and family income were studied. The cutoff point chosen for excessively high ABI was 1.3. Continuous variables were dichotomized. The chi-square test was used for statistical analysis and results with p ≤ 0.05 were considered significant. Results A total of 309 patients were interviewed, 65% were women, 26% had graduated from secondary education and 77% had a family income equal to or less than three times the minimum salary. The frequency of excessively high ABI (≥ 1.3) was 16.5%. Bivariate analyses detected no statistically significant correlations between excessively high ABI (≥ 1.3) and the sociodemographic variables studied (sex, age, time since diagnosis of diabetes mellitus, family income and educational level). Conclusions The frequency of high ABI among this sample of diabetics was 16.5%. We did not detect correlations between the sociodemographic variables (sex, age, duration of DM, educational level and family income) and high ABI.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Índice Tobillo Braquial/historia , Angiopatías Diabéticas/diagnóstico por imagen , Enfermedad Arterial Periférica/diagnóstico , Calcificación Vascular/patología , Epidemiología DescriptivaRESUMEN
Chronic renal disease (CRD) accelerates the development of atherosclerosis. The potent protease cathepsin S cleaves elastin and generates bioactive elastin peptides, thus promoting vascular inflammation and calcification. We hypothesized that selective cathepsin S inhibition attenuates atherogenesis in hypercholesterolemic mice with CRD. CRD was induced by 5/6 nephrectomy in high-fat high-cholesterol fed apolipoprotein E-deficient mice. CRD mice received a diet admixed with 6.6 or 60 mg/kg of the potent and selective cathepsin S inhibitor RO5444101 or a control diet. CRD mice had significantly higher plasma levels of osteopontin, osteocalcin, and osteoprotegerin (204%, 148%, and 55%, respectively; P < 0.05), which were inhibited by RO5444101 (60%, 40%, and 36%, respectively; P < 0.05). Near-infrared fluorescence molecular imaging revealed a significant reduction in cathepsin activity in treated mice. RO5444101 decreased osteogenic activity. Histologic assessment in atherosclerotic plaque demonstrated that RO5444101 reduced immunoreactive cathepsin S (P < 0.05), elastin degradation (P = 0.01), plaque size (P = 0.01), macrophage accumulation (P < 0.01), growth differentiation factor-15 (P = 0.0001), and calcification (alkaline phosphatase activity, P < 0.01; osteocalcin, P < 0.05). Furthermore, cathepsin S inhibitor or siRNA significantly decreased expression of growth differentiation factor-15 and monocyte chemotactic protein-1 in a murine macrophage cell line and human primary macrophages. Systemic inhibition of cathepsin S attenuates the progression of atherosclerotic lesions in 5/6 nephrectomized mice, serving as a potential treatment for atherosclerosis in patients with CRD.
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Apolipoproteínas E/deficiencia , Aterosclerosis/patología , Catepsinas/antagonistas & inhibidores , Fallo Renal Crónico/enzimología , Fallo Renal Crónico/patología , Animales , Arterias/enzimología , Arterias/patología , Aterosclerosis/complicaciones , Biomarcadores/sangre , Catepsinas/metabolismo , Quimiocina CCL2/metabolismo , Factor 15 de Diferenciación de Crecimiento/metabolismo , Humanos , Interferón gamma/farmacología , Fallo Renal Crónico/sangre , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Osteogénesis/efectos de los fármacos , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Calcificación Vascular/complicaciones , Calcificación Vascular/patologíaRESUMEN
OBJECTIVE: It has been suggested that pineal gland calcifications (PGC) represent a risk factor for stroke; however, information comes from a single retrospective hospital-based registry. We aimed to validate this association in a population-based study conducted in rural Ecuador. METHODS: Atahualpa residents aged ≥60 years were identified during a door-to-door survey and invited to undergo neuroimaging studies (CT/MRI) for identification and rating PGC and lesions consistent with cerebral infarcts and hemorrhages. Cardiovascular health (CVH) status was assessed according to the American Heart Association criteria, and clinical strokes were identified by the use of a validated field instrument and confirmed by neurologists. RESULTS: Out of 248 participants (mean age 70±8 years, 59% women, 73% with poor CVH), 137 (55%) had PGC and 39 (16%) had strokes (silent in 28 cases). PGC were noted in 61% versus 54% persons with and without stroke, respectively. After adjusting for age, sex and cardiovascular health, logistic and ordinal logistic regression models showed no association between any evidence (p=0.916) or severity (p=0.740) of PGC and stroke. CONCLUSION: PGC is not associated with stroke in this population of community-dwelling elders, where prevalence of PGC and stroke are similar to those found in other regions.
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Infarto Cerebral/patología , Glándula Pineal/patología , Accidente Cerebrovascular/patología , Calcificación Vascular/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Infarto Cerebral/diagnóstico , Ecuador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Calcificación Vascular/patologíaRESUMEN
This study investigated the alteration of gene expression profiles in order to gain a deeper understanding into the molecular mechanism involved in different processes of vascular calcification (VC). Sprague Dawley (SD) rats were injected with 300,000 µg/kg vitamin D3 and gavaged with 25 mg/kg nicotine for 8 or 16 weeks to create 8- and 16-week VC calcification groups. Histological analysis and quantification of aortic calcium content were used to determine the severity of vascular calcification. The suppression subtractive hybridization (SSH) method was employed to screen for up and downregulated genes in early and later phases of vascular calcification. Changes in calcium and phosphorus levels in tissue were used as markers of vascular calcification. Quantification of aortic calcium content revealed that vascular calcification might regress over time. In the early phase of vascular calcification, many calcification-promoting genes were upregulated, including ossification, oxidation, and inflammatory genes. In contrast, in later phase of vascular calcification, various calcification-inhibitor genes were highly expressed, including pyrophosphoric acid synthesis genes, glutamate signal peptide-related, reduction activity, and apoptosis regulation genes. The relatively higher expression of calcification-inhibitor genes compared to that of calcification-promoting genes might explain the genetic mechanism leading to the regression of vascular calcification. Therefore, this study provides a genomic basis to facilitate understanding of the molecular mechanism underlying vascular calcification regression.
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Transcriptoma , Calcificación Vascular/metabolismo , Fosfatasa Alcalina , Animales , Aorta/metabolismo , Aorta/patología , Calcio/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Masculino , Redes y Vías Metabólicas , Fósforo/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Calcificación Vascular/genética , Calcificación Vascular/patologíaRESUMEN
It has been described renal damage in rats with vascular calcification. The organic anion transporter 5 (Oat5) is only expressed in kidney, and its urinary excretion was proposed as potential early biomarker of renal injury. The aim of this study was to evaluate the Oat5 renal expression and its urinary excretion in an experimental model of vascular calcification in comparison with traditional markers of renal injury. Vascular calcification was obtained by the administration of an overdose of vitamin D3 (300,000 IU/kg, b.w., i.m.) to male Wistar rats. Oat5 urinary abundance was evaluated by Western blotting. Traditional markers of renal injury, such as creatinine and urea plasma levels, urinary protein levels, and urinary alkaline phosphatase (AP) activity, were determined using commercial kits. Histology was assessed by hematoxylin/eosin staining. Oat5 renal expression was evaluated by Western blotting and by immunohistochemistry. An increased expression of Oat5 in renal homogenates, in apical membranes, and in its urinary excretion was observed in rats with vascular calcification. The traditional parameters used to evaluate renal function were not modified, with the exception of histology. It is possible to postulate the urinary excretion of Oat5 as a potential noninvasive biomarker of renal injury associated with vascular calcification.
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Transportadores de Ácidos Dicarboxílicos/metabolismo , Transportadores de Ácidos Dicarboxílicos/orina , Riñón/metabolismo , Calcificación Vascular/orina , Fosfatasa Alcalina/orina , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aorta Abdominal/fisiopatología , Presión Sanguínea , Calcio/metabolismo , Inmunohistoquímica , Masculino , Ratas , Ratas Wistar , Sístole , Calcificación Vascular/patología , Calcificación Vascular/fisiopatologíaRESUMEN
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% 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.
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Enfermedad de la Arteria Coronaria/etiología , Diabetes Mellitus Tipo 1/complicaciones , Retinopatía Diabética/etiología , Calcificación Vascular/etiología , Adulto , Enfermedad de la Arteria Coronaria/patología , Diabetes Mellitus Tipo 1/patología , Retinopatía Diabética/patología , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Calcificación Vascular/patologíaRESUMEN
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.
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/etiología , Diabetes Mellitus Tipo 1/complicaciones , Retinopatía Diabética/etiología , Calcificación Vascular/etiología , Enfermedad de la Arteria Coronaria/patología , Diabetes Mellitus Tipo 1/patología , Retinopatía Diabética/patología , Métodos Epidemiológicos , Factores de Riesgo , Calcificación Vascular/patologíaRESUMEN
Vascular calcification is highly prevalent in patients with chronic kidney disease and has a progressive course. Several cardiovascular and uremia-related risk factors, such as abnormalities in mineral metabolism, contribute to the development of vascular calcification, although the pathophysiological mechanisms are still unclear. The presence and extent of vascular calcification is associated with an increased risk of cardiovascular events and mortality. By contrast, patients who do not have calcification seem to have a good prognosis, with minimal or no calcification progression over an extended period of time. A number of noninvasive imaging methods are available to detect vascular calcification and may help clinicians to make therapeutic decisions. Cardiac CT remains the reference standard to detect and quantify coronary artery, aortic and cardiac valve calcification. However, the high cost of equipment, the inability to perform in-office testing and the expertise required limit its use on a routine basis. Other imaging methods, such as planar X-ray, ultrasound and echocardiography, are appropriate alternatives to evaluate vascular and valvular calcification. In this review, we discuss the noninvasive imaging methods most frequently used to assess vascular and valvular calcification, with their advantages and limitations.
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Vasos Sanguíneos/patología , Diagnóstico por Imagen , Fallo Renal Crónico/patología , Calcificación Vascular/diagnóstico , Aorta Abdominal/patología , Aorta Torácica/patología , Velocidad del Flujo Sanguíneo , Enfermedades Cardiovasculares/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Vasos Coronarios/patología , Progresión de la Enfermedad , Electrocardiografía , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patología , Calcificación Vascular/fisiopatología , Rigidez VascularRESUMEN
BACKGROUND: Cardiovascular disease in chronic kidney disease (CKD) has peculiar characteristics. The aim of this study was to analyze atherosclerosis, vascular calcification and nitration in arteries from CKD patients. METHODS: External iliac and renal artery segments from 27 stage 5 CKD patients and 25 donor controls, respectively, were collected during the transplantation procedure. RESULTS: CKD patients presented a significantly higher degree of lesion. In a large proportion (72%) of CKD patients, we observed vascular calcifications. Immunohistochemistry for nitrotyrosine revealed a significant increase in nitrotyrosine production in arteries from CKD patients compared with control donors. In addition, within CKD patients, nitrotyrosine staining was significantly stronger in arteries with media calcification when compared with arteries without media calcification. CONCLUSION: The arteriopathy in the CKD patients appears in an early age and seems to be distinct from the arteriopathy of the general population, especially due to intense calcification and vascular oxidative stress.
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Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/patología , Proteínas/metabolismo , Calcificación Vascular/patología , Adulto , Aterosclerosis/patología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Renal/metabolismo , Arteria Renal/patología , Factores de Riesgo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
This study presents the results of Raman spectroscopy applied to the classification of arterial tissue based on a simplified model using basal morphological and biochemical information extracted from the Raman spectra of arteries. The Raman spectrograph uses an 830-nm diode laser, imaging spectrograph, and a CCD camera. A total of 111 Raman spectra from arterial fragments were used to develop the model, and those spectra were compared to the spectra of collagen, fat cells, smooth muscle cells, calcification, and cholesterol in a linear fit model. Non-atherosclerotic (NA), fatty and fibrous-fatty atherosclerotic plaques (A) and calcified (C) arteries exhibited different spectral signatures related to different morphological structures presented in each tissue type. Discriminant analysis based on Mahalanobis distance was employed to classify the tissue type with respect to the relative intensity of each compound. This model was subsequently tested prospectively in a set of 55 spectra. The simplified diagnostic model showed that cholesterol, collagen, and adipocytes were the tissue constituents that gave the best classification capability and that those changes were correlated to histopathology. The simplified model, using spectra obtained from a few tissue morphological and biochemical constituents, showed feasibility by using a small amount of variables, easily extracted from gross samples.