RESUMEN Introducción: La osteodistrofia renal es una complicación frecuente de la enfermedad renal crónica, lo que sumado a la aterogénesis acelerada, presente en estos pacientes, determina un riesgo cardiovascular incrementado, particularmente en los casos con tratamiento dialítico. Objetivo: Describir las alteraciones del metabolismo óseo-mineral en la enfermedad renal crónica avanzada con y sin tratamiento dialítico. Material y Métodos: Se efectuó un estudio observacional descriptivo y transversal en 106 pacientes con enfermedad renal crónica avanzada, que se agruparon según recibieran o no tratamiento dialítico (53 hemodializados y 53 no). Estos grupos se compararon en cuanto a variables demográficas, factores de riesgo aterosclerótico y parámetros bioquímicos e imagenológicos relacionados con el metabolismo óseo-mineral. Resultados: Predominaron los pacientes entre 60 y 74 años, el sexo masculino, el color de la piel diferente al blanco, la hipertensión arterial, la dislipidemia y la osteopenia, en tanto las manos, columna lumbosacra y pelvis fueron los sitios óseos más afectados. De las diferencias encontradas entre los grupos las que alcanzaron significación estadística fueron: en hemodializados la edad media y las cifras de fosfatasa alcalina, fósforo y producto calcio*fósforo resultaron superiores; mientras que la osteoesclerosis craneal, la fractura torácica y la reabsorción en manos representaron las alteraciones radiológicas más prevalentes. Además, las determinaciones séricas de calcio, fósforo y fosfatasa alcalina mostraron las correlaciones lineales más fuertes con la densidad mineral ósea. Conclusiones: Se comprueba una mayor afectación del metabolismo óseo-mineral en los pacientes con enfermedad renal crónica avanzada hemodializados, lo que reafirma la necesidad de incorporar al seguimiento el survey y la densitometría ósea.

ABSTRACT Introduction: Renal osteodystrophy is a frequent complication of chronic kidney disease, which added to the accelerated atherogenesis present in these patients, determines an increased cardiovascular risk, particularly in cases with dialysis treatment. Objective: To describe the alterations in bone mineral metabolism in advanced chronic kidney disease with and without dialysis treatment. Material and Methods: An observational, descriptive and cross-sectional study was carried out in 106 patients with advanced chronic kidney disease who were grouped according to whether or not they received dialysis treatment (53 hemodialyzed and 53 non-hemodialyzed). These groups were compared in terms of demographic variables, atherosclerotic risk factors, and biochemical and imaging parameters related to bone mineral metabolism. Results: Patients between 60 and 74 years old; males; of non-white skin color; and suffering from arterial hypertension, dyslipidemia and osteopenia predominated in the study. The hands, lumbosacral spine, and pelvis were the most affected bone sites. As for the differences found between the groups, those that reached statistical significance were: in hemodialysis patients, the average age and the values of alkaline phosphatase, phosphorus and calcium-phosphorus product were higher; while cranial osteosclerosis, thoracic fracture and hand resorption represented the most prevalent radiological alterations. In addition, serum calcium, phosphorus, and alkaline phosphatase measurements showed the strongest linear correlations with bone mineral density. Conclusions: A greater affectation of bone mineral metabolism is verified in patients with advanced chronic kidney disease on hemodialysis, which reaffirms the need to incorporate the survey and bone densitometry to the follow-up of patients.

RESUMEN Introducción: Las investigaciones dirigidas a la identificación de los factores de riesgo aterogénico en niños y adolescentes, demuestran que las enfermedades, como consecuencia de la aterosclerosis en el adulto, se generan desde edades tempranas de la vida. Objetivo: Identificar las señales aterogénicas tempranas en adolescentes. Método: Se realizó una investigación observacional, descriptiva, de corte transversal, que incluyó 298 adolescentes de 11 a 16 años. Se identificaron las variables sobrepeso-obesidad, hipertensión arterial, tabaquismo, inactividad física y dieta inadecuada. Resultados: El 20,5 % de los adolescentes resultaron prehipertensos y el 2,3 % hipertensos. El 40,3 % tenía alteraciones del peso corporal y 44,3 % obesidad abdominal. La señal aterogénica temprana más frecuente fue la actividad física ligera en el 36,6 %. Conclusiones: Las señales aterogénicas tempranas más frecuentes son la obesidad abdominal, el sobrepeso y el sedentarismo, en ese orden.

ABSTRACT Introduction: Investigations aimed at identifying atherogenic risk factors in children and adolescents show that diseases, as a consequence of atherosclerosis in adults, are generated from an early age of life. Objective: To identify early atherogenic signs in adolescents. Method: An observational, descriptive, cross-sectional study was carried out, which included 298 adolescents from 11 to 16 years of age. The variables overweight-obesity, arterial hypertension, smoking, physical inactivity and inadequate diet were identified. Results: 20.5% of adolescents were prehypertensive and 2.3% hypertensive. 40.3% had changes in body weight and 44.3% had abdominal obesity. The most representative early atherogenic sign, related to lifestyles, was light physical activity in 36.6%. Conclusions: The early atherogenic signs most frequently identified are abdominal obesity, overweight and sedentary lifestyle, in this order.

In the modern world, cardiovascular diseases have a special place among the most common causes of death. Naturally, this widespread problem cannot escape the attention of scientists and researchers. One of the main conditions preceding the development of fatal cardiovascular diseases is atherosclerosis. Despite extensive research into its pathogenesis and possible prevention and treatment strategies, many gaps remain in our understanding of this disease. For example, the concept of multiple low-density lipoprotein modifications was recently stated, in which desialylation is of special importance. Apart from this, sialic acids are known to be important contributors to processes such as endothelial dysfunction and inflammation, which in turn are major components of atherogenesis. In this review, we have collected information on sialic acid metabolism, analyzed various aspects of its implication in atherosclerosis at different stages, and provided an overview of the role of particular groups of enzymes responsible for sialic acid metabolism in the context of atherosclerosis. world death Naturally researchers strategies disease example lowdensity low density stated importance inflammation atherogenesis review stages

Resumo Vastas evidências científicas de resultados de ensaios clínicos, pré-clínicos, epidemiológicos e genéticos mostraram uma associação causal entre o aumento de triglicerídeos (TG), lipoproteínas ricas em TG (LRT) e seus remanescentes para doença cardiovascular aterosclerótica (DCA). O acúmulo de LRT circulante pode explicar, em parte, o risco cardiovascular residual observado em pacientes tratados de maneira eficaz para reduzir seus níveis de LDL, no entanto, o risco de DCA persiste. É fundamental que no estudo do perfil lipídico seja considerada a determinação ou estimativa dessas lipoproteínas, somada à dosagem de TG plasmáticos. O objetivo desta revisão foi atualizar o conhecimento sobre os níveis aumentados de TG, LRT e seus remanescentes, fornecer alternativas para sua determinação e compreender os mecanismos que envolvem as LRT no desenvolvimento acelerado da aterosclerose. A atualização dos diferentes parâmetros associados ao aumento de TG, e seus valores de corte ou limites de decisão clínica de acordo com a classificação do risco de DCE para cada paciente, permitirá o redesenho de um relatório de resultados que será muito útil para o médico e o paciente quanto às condutas preventivas e terapêuticas da DCE.

Abstract Vast scientific evidence from clinical, preclinical, epidemiological, and genetic trial results show a causal association between increased triglycerides (TG), TG-rich lipoproteins (TRL), and their remnants for atherosclerotic cardiovascular disease (ASCVD). The accumulation of circulating LRT may explain, in part, the residual cardiovascular risk observed in patients successfully treated to reduce their LDL levels, however, the risk of ASCVD still persists. It is essential that in the assessment of the lipid profile, the determination or estimation of these lipoproteins be considered, added to the measurement of plasmatic TG. The objective of this review is to update the knowledge about the increased levels of TG, LRT and their remnants, proprovide alternatives for their determination and understand the mechanisms that involve LRT in the accelerated development of atherosclerosis. Updating the different parameters associated with increased TG and their cut-off values or clinical decision limits according to the ASCVD risk classification for each patient will allow for the redesign of a results report that will be very useful for the physician and the patient regarding the preventive and therapeutic behaviours of the ASCVD.

Resumen Una vasta evidencia científica de resultados de ensayos clínicos, preclínicos, epidemiológicos y genéticos, mostraron una asociación causal entre el aumento de triglicéridos (TG), lipoproteínas ricas en TG (LRT) y sus remanentes para la enfermedad cardiovascular aterosclerótica (ECA). La acumulación de LRT circulantes puede explicar, en parte, el riesgo cardiovascular residual que se observa en pacientes eficazmente tratados para reducir sus niveles de LDL; sin embargo, persiste el riesgo de ECA. Es imprescindible que en el estudio del perfil lipídico se considere la determinación o estimación de estas lipoproteínas, sumada a la medida de TG plasmáticos. El objetivo de la presente revisión fue actualizar el conocimiento acerca de los niveles incrementados de TG, de LRT y sus remanentes, brindar alternativas para su determinación y comprender los mecanismos que involucran a las LRT en el desarrollo acelerado de la aterosclerosis. La actualización de los diferentes parámetros asociados al aumento de TG y sus valores de corte o límites de decisión clínica según la clasificación del riesgo de ECA para cada paciente, permitirá el rediseño de un informe de resultados que será de gran utilidad para el médico y el paciente con respecto a las conductas preventivas y terapéuticas de la ECA.

Abstract Background In the atherosclerotic plaque microenvironment, oxidized phospholipids expressed in the oxidized low-density lipoprotein (oxLDL) surface bind to scavenger receptors of macrophages eliciting foam cell formation and plaque progression. Auto-antibodies against oxLDL (oxLDL-Ab) interact with oxidative epitopes leading to the formation of immune complexes that are unable to interact with macrophage receptors, thus abrogating atherogenesis. Release of oxLDL-Ab by B cells involves interleukin 5 and Th2 response, which in turn are potentiated by HDL. Thereby, we hypothesized that individuals with higher levels of HDL-C may plausibly display elevated titers of oxLDL-Ab. Objective To evaluate the relationship between HDL-C and oxLDL-Ab levels. Methods Asymptomatic individuals (n = 193) were grouped according to their HDL-C concentration to one of three categories: low (< 68 mg/dL), intermediate (68 to 80 mg/dL) or high (> 80 mg/dL). P values < 0.05 were considered statistically significant. Results Our analysis included 193 individuals (mean age: 47 years; male: 26.3%). Compared to individuals in the lowest HDL-C tertile, those in the highest tertile were older (36 versus 53 years; p = 0.001) and less frequently male (42.6% versus 20.9%; p = 0.001). Mean values of oxLDL-Ab increased as the HDL-C group escalated (0.31, 0.33 and 0.43 units, respectively; p = 0.001 for trend). Simple linear regression found a significant, positive relationship between the independent variable, HDL-C, and the dependent variable, oxLDL-Ab (R = 0.293; p = 0.009). This relation remained significant (R = 0.30; p = 0.044), after adjustment by covariates. Apolipoprotein AI levels were also related to oxLDL-Ab in both simple and adjusted linear regression models. Conclusion HDL-C and oxLDL-Ab are independently related. microenvironment lowdensity density (oxLDL progression Autoantibodies Auto antibodies oxLDLAb Ab (oxLDL-Ab atherogenesis Th response HDL Thereby HDLC C oxLDLAb. Ab. n categories ( 6 mg/dL, mgdL mg/dL , mg dL (6 8 > mg/dL. . 005 0 05 0.0 19 mean age 4 years 26.3%. 263 26.3% 26 3 26.3%) 36 (3 0001 001 42.6% 426 42 (42.6 20.9% 209 20 9 0.001. 0.31, 031 31 (0.31 033 33 0.3 043 43 0.4 units respectively 0.00 trend. trend trend) variable HDLC, C, R 0.293 0293 293 0.009. 0009 0.009 009 0.009) 0.30 030 30 0.044, 0044 0.044 044 0.044) covariates models 00 0. 1 26.3 2 000 42.6 (42. 20.9 0.31 03 (0.3 04 0.29 029 29 004 0.04 26. 42. (42 20. (0. 0.2 02 (4 (0

Resumo Fundamento No microambiente da placa aterosclerótica, os fosfolipídios oxidados expressos na superfície de lipoproteína de baixa densidade oxidada (oxLDL) se ligam a receptores scavenger em macrófagos provocando a formação de células espumosas e a progressão da placa. Autoanticorpos contra oxLDL (oxLDL-Ab) interagem com epítopos oxidativos levando à formação de imunocomplexos que são incapazes de interagir com receptores de macrófagos, assim suprimindo a aterogênese. A liberação de oxLDL-Ab pelas células B envolve a resposta da interleucina 5 e Th2, que por sua vez são potencializadas pela HDL. Assim, levantamos a hipótese de que indivíduos com níveis mais altos de HDL-C podem apresentar níveis elevados de oxLDL-Ab. Objetivo Avaliar a relação entre os níveis de HDL-C e oxLDL-Ab. Métodos Indivíduos assintomáticos (n = 193) foram agrupados de acordo com sua concentração de HDL-C para uma das três categorias seguintes: baixa (< 68 mg/dL), intermediária (de 68 a 80 mg/dL) ou alta (> 80 mg/dL). Os valores p < 0,05 foram considerados estatisticamente significativos. Resultados Nossa análise incluiu 193 indivíduos (média etária: 47 anos; masculino: 26,3%). Em comparação com os indivíduos no menor tercil de HDL-C, os mais elevados foram mais velhos (36 versus 53 anos; p = 0,001) e, menos frequentemente, masculinos (42,6% versus 20,9%; p = 0,001). Os valores médios de oxLDL-Ab aumentaram à medida que o grupo HDL-C aumentou (0,31, 0,33 e 0,43 unidades, respectivamente; p = 0,001 para tendência). A regressão linear simples encontrou uma relação significativa e positiva entre a variável independente, HDL-C, e a variável dependente, oxLDL-Ab (R = 0,293; p = 0,009). Essa relação manteve-se significativa (R = 0,30; p = 0,044), após ajuste por covariáveis. Os níveis de apolipoproteína AI também estiveram relacionados a oxLDL-Ab nos modelos de regressão linear simples e ajustada. Conclusões HDL-C e oxLDL-Ab estão independentemente relacionados. aterosclerótica (oxLDL oxLDLAb Ab (oxLDL-Ab aterogênese Th2 Th HDL Assim HDLC C oxLDLAb. Ab. n seguintes ( 6 mg/dL, mgdL mg/dL , mg dL 8 > mg/dL. . 005 0 05 0,0 significativos 19 média etária 4 anos masculino 26,3%. 263 26,3% 26 3 26,3%) HDLC, C, 36 (3 0001 001 frequentemente 42,6% 426 42 (42,6 20,9% 209 20 9 0,001. 0,31, 031 31 (0,31 033 33 0,3 043 43 0,4 unidades respectivamente 0,00 tendência. tendência tendência) independente dependente R 0,293 0293 293 0,009. 0009 0,009 009 0,009) mantevese manteve 0,30 030 30 0,044, 0044 0,044 044 0,044) covariáveis ajustada 00 0, 1 26,3 2 000 42,6 (42, 20,9 0,31 03 (0,3 04 0,29 029 29 004 0,04 26, 42, (42 20, (0, 0,2 02 (4 (0

Abstract: This manuscript is an addendum to the positioning around the diagnosis and treatment of dyslipidemias of ANCAM and the joint group of associated medical societies, already published. It is the first part of a wider reflection aimed on refute several of the theses and arguments of a group of clinicians and researchers who question the validity of the “cholesterol hypothesis”, the usefulness and safety of statins and the most modern inhibitors of proprotein convertase of subtilisin/kexin type 9 (iPCSK9,) and the role of saturated fatty acids consumed in the usual diet in the atherosclerotic risk. This iconoclastic point of view is dangerous insofar as it undermines the scaffolding that supports the primary and secondary prevention of atherosclerosis. In this section of the manuscript, only the cholesterol hypothesis is discussed. The data of comparative zoology are reviewed, and several experimental animal models are analyzed, both supporting the link between cholesterol and the appearance and evolution of atherosclerotic lesions. The methodology and the results of the Study of the 7 Countries are defended and are exposed the numerous epidemiological, pathological, clinical and interventional evidences, which in our opinion give a solid sustenance to the cholesterol hypothesis. Based on this knowledge it is criticized the LDL cholesterol values currently considered adequate. Furthermore, the so-called residual risk is considered, as well as the conflicting evidence about the usefulness of statins in elderly patients.

Resumen: Este manuscrito es un apéndice del posicionamiento en torno al diagnóstico y tratamiento de las dislipidemias de la ANCAM y el grupo de las sociedades médicas asociadas, previamente publicado. Es la primera parte de un trabajo más amplio enfocado a refutar varias de las tesis y argumentos de un grupo de clínicos e investigadores que ponen en duda la validez de la “hipótesis del colesterol”, la utilidad y seguridad de las estatinas y los más modernos inhibidores de la proproteína convertasa de la subtilisina/kexina tipo 9 (iPCSK9) y el papel de los ácidos grasos saturados consumidos en la dieta habitual en el riesgo ateroscleroso. Este punto de vista iconoclástico es peligroso porque socava el andamiaje que soporta la prevención primaria y secundaria de la aterosclerosis. En esta primera sección del manuscrito, se discute sólo la hipótesis del colesterol. Se revisan los datos de zoología comparada y se analizan varios modelos animales de experimentación, que apoyan la liga entre el colesterol y la aparición y evolución de las lesiones aterosclerosa. Se defienden la metodología y los resultados del estudio de los 7 países y se exponen las numerosas evidencias epidemiológicas, patológicas, clínicas e intervencionistas, que a nuestro juicio dan un sustento sólido a la hipótesis del colesterol. Se critican también, en base a ese conocimiento, los valores de colesterol LDL actualmente considerados adecuados, a la vez que se discute el llamado riesgo residual y las evidencias conflictivas acerca de la utilidad de las estatinas en pacientes ancianos.

Resumo Fundamentos: Alimentos funcionais, como a linhaça, têm sido consumidos com frequência para prevenção da aterosclerose. Objetivos: Avaliar os efeitos da linhaça sobre a aterogênese em coelhos submetidos a uma dieta rica em colesterol. Métodos: Trinta coelhos albinos machos foram randomizados em três grupos com base em um tratamento dietético por 12 semanas: grupo controle (G1), dieta padrão; dieta rica em colesterol (G2), dieta padrão mais 0,25% de colesterol proveniente de ovos liofilizados; e dieta rica em colesterol mais linhaça (G3), dieta semelhante à do G2 adicionada de linhaça. Análise bioquímica (colesterol total [CT], lipoproteína de alta densidade [HDL-colesterol], lipoproteína de baixa densidade [LDL-colesterol] e triglicérides) e imunohistoquímica (molécula de adesão intercelular 1 [ICAM-1] e fator de necrose tumoral alfa [TNF-α]) foram realizadas em todos os grupos. Valores de p < 0,05 indicaram significância estatística. Resultados: Às 12 semanas, os níveis séricos de CT aumentaram significativamente nos grupos G2 e G3 em comparação com o G1. Os níveis séricos de LDL-colesterol foram mais altos no grupo G2, e o aumento no grupo G3 foi cerca de seis vezes menor do que no G2. Os níveis de HDL-colesterol aumentaram em todos os grupos, com o maior aumento observado no G2. Os níveis de triglicérides no G3 reduziram em ~70% e diferiram significativamente entre o G1 e G3 (p = 0,034) e G2 e G3 (p = 0,015). Níveis de ICAM-1 aumentaram apenas no segmento aórtico 4 no G3. Os níveis de TNF-α no grupo G3 foram semelhantes aos do grupo controle, enquanto os níveis no G2 foram maiores do que o dobro em relação aos do grupo controle (p < 0,05). Conclusões: O grupo alimentado com uma dieta funcional (linhaça) mostrou redução no desenvolvimento de aterosclerose, níveis séricos mais baixos de triglicérides e níveis mais baixos de TNF-α à imunohistoquímica. (Int J Cardiovasc Sci. 2018;31(2)114-122)

Abstract Background: Functional foods such as flaxseed have been commonly consumed to prevent atherosclerosis. Objectives: To assess the effects of flaxseed in atherogenesis in rabbits consuming a high-cholesterol diet. Methods: Thirty male albino rabbits were randomized to three groups based on a 12-week dietary treatment: control group (G1), standard diet; high-cholesterol diet (G2), standard diet plus 0.25% cholesterol from lyophilized eggs; and high-cholesterol plus flaxseed (G3), similar diet as G2 plus flaxseed. Biochemical (total cholesterol [TC], high-density lipoprotein [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) and immunohistochemical (intercellular adhesion molecule 1 [ICAM-1] and tumor necrosis factor alpha [TNF-α]) analyses were performed in all groups. P values < 0.05 indicated statistical significance. Results: At 12 weeks, serum TC levels increased significantly in G2 and G3 compared with G1. Serum LDL-C levels were higher in group G2, and the increase in group G3 was approximately six times lower than that in G2. HDL-C levels increased in all groups, with the highest increase observed in G2. Triglycerides levels in G3 decreased by ~70% and differed significantly in G1 and G3 (p = 0.034) and G2 and G3 (p = 0.015). ICAM-1 levels increased only in aortic segment 4 in G3. TNF-α levels in G3 were similar to those in the control group, while the levels in G2 were greater than twice as those in the control group (p < 0.05). Conclusions: The group fed with a functional diet (flaxseed) showed decreased development of atherosclerosis, reduced serum triglycerides levels, and lower TNF-α levels on immunohistochemistry.

Abstract Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI= 2.41-27.51, P < 0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population.

Abstract Background and aims: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. Methods and results: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. Conclusions: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Resumen El endotelio se puede definir como una monocapa que separa los tejidos de la sangre. Las células endoteliales tienen una multitud de funciones que son específicas a su localización. La principal función del endotelio es regular el flujo y la perfusión sistémicos a través de cambios en el diámetro y en el tono vascular. La disfunción endotelial (DE) comprende una pérdida del balance entre los factores vasodilatadores y vasoconstrictores derivados del endotelio, donde el estado vasoconstrictor llega a ser dominante, llevando a cambios patofisiológicos progresivos. Colectivamente, estos cambios endoteliales exhiben características proinflamatorias, prooxidantes, proliferativas, procoagulantes y de adhesión vascular. El proceso de aterosclerosis comienza temprano en la vida y la DE contribuye a la aterogénesis en cada fase de la aterosclerosis. La disfunción endotelial es un marcador de la aterosclerosis y es el precursor más claramente definido de la aterosclerosis. El estrés oxidativo es el mecanismo celular subyacente para el desarrollo de la DE. La inflamación es otro mecanismo subyacente a la DE. Hay una relación causal entre el estrés oxidativo y la inflamación. El estrés oxidativo puede amplificar las vías de señalización vasculares inflamatorias y la inflamación incrementa el estrés oxidativo. La función endotelial puede ser medida mediante su capacidad para ejecutar varias funciones, incluyendo el tono vasomotor, la expresión de moléculas de adhesión y el mantenimiento de un microambiente antitrombótico. En la investigación clínica la función endotelial se detecta midiendo los cambios en el tono vasomotor en respuesta a varios estímulos. Un número de biomarcadores se han identificado y utilizado como indicadores de función endotelial.

Abstract The endothelium could be defined as a cellular monolayer separating all tissues from the bloodflow. Endothelial cells have a myriad of functions that are specific to their location. The main function of endothelium is to regulate systemic blood flow and tissue perfusión through changes in vessel diameter and tone vascular. Endothelial dysfunction (ED) comprises a loss of balance between endothelial-derived vasodilatory and vasoconstrictory factors, where the pro-vasoconstrictory state become dominant, leading to progressive pathophysiological changes. Collectively, these endothelial changes exhibit proinflammatory, pro-oxidant, proliferative, procoagulation and pro-vascular adhesion features. The process of atherosclerosis begins early in life, and endothelial dysfunction contributes to atherogenesis at every phase of atherosclerosis. Endothelial dysfunction is a marker of atherosclerosis and it is the most clearly defined early precursor of atherosclerosis. Oxidative stress to be the common underlying cellular mechanisms for the development of ED. Inflammation is another common underlying mechanism of ED. There is a causal relationship between oxidative stress and inflammation. Oxidative stress may amplify vascular inflammation signalling pathways, and conversely inflammation increases oxidative stress. Endothelial function can be assessed by assaying its capacity to perform its various functions, including regulation of vasomotor tone, expression of adhesion molecules and maintenance of an anti-thrombotic microenvironment. In clinical Research, endothelial function is tipically assessed by measuring changes in vasomotor tone in response to various stimuli. A number of biomarkers have been identified and used as indicators of endothelial function.

Resumen La hipoglicemia aguda y crónica, inducida por insulina u otros antidiabéticos orales, en un contexto terapéutico, constituye un factor de riesgo cardiovascular, generador de disfunción endotelial y aterogénesis a través de mecanismos proinflamatorios, tanto o más relevante que la hiperglicemia, con el agravante de inducir muerte súbita arritmogénica e isquémica. Conclusión: La hipoglicemia constituye una amenaza real para el miocardio, no solo por sus efectos proarrítmicos inmediatos, que pueden relacionarse con síndrome de muerte súbita, sino también por los efectos proinflamatorios y aterogénicos que constituyen un factor de riesgo importante para el desarrollo de enfermedad cardiovascular. Por tanto, es deseable, y clínicamente pertinente, evitar los episodios de hipoglicemia de cualquier intensidad y duración en todo tipo de paciente diabético, en especial en aquellos que presenten un sustrato miocárdico patológico que confiera incremento del riesgo de muerte súbita: función sistólica comprometida, arritmias ventriculares, fibrilación atrial, enfermedad coronaria, miocardiopatía hipertrófica, genotipo arritmogénico y antecedentes de reanimación.

Abstract Acute or chronic hypoglycaemia, induced by insulin or other oral antidiabetic drugs cin a therapeutic context, constitutes a cardiovascular risk factor. It leads to endothelial dysfunction and atherogenesis through pro-inflammatory mechanisms, as much as or more important than hyperglycaemia, with the aggravating factor of inducing arrhythmogenic and ischaemic sudden death. Conclusion: Hypoglycaemia is a real threat for the myocardium, not only due to its immediate pro-arrhythmic effects, that may be associated with sudden death syndrome, but also due to the pro-inflammatory and atherogenic effects. These are all significant risk factors for the development of cardiovascular disease, making it desirable, and clinically relevant to prevent hypoglycaemic episodes of any intensity and duration in any type of diabetic patient. This is particularly important in those that have a pathological myocardial substrate that can lead to an increase in the risk of sudden death: compromised systole function, ventricular arrhythmias, atrial fibrillation, coronary disease, hypertrophic cardiomyopathy, arrhythmogenic genotype, and a history of resuscitation.

A aterosclerose é a doença vascular mais prevalente, o que motiva numerosas pesquisas sobre sua patogênese. As lipoproteínas podem ser modificadas por meio de mecanismos de oxidação e de acetilação entre outros, em nível de seus componentes lipídicos como proteicos, tornando-se aterogênicas. As apolipoproteínas B100 modificadas (ApoB100m), desempenham um papel ativo no desenvolvimento de lesões ateroscleróticas em conjunto com outros fatores de risco. Elas têm a capacidade de produzir resposta imune que conduz à produção de anticorpos e subsequente formação de complexos imunes. A importância de anticorpos contra a ApoB100m na aterogênese ainda não é clara, existindo dados contraditórios sobre se seu papel é de proteção ou aterogênico. Foram estabelecidos dois objetivos. Determinar os níveis de complexos imunes circulantes IgM-ApoB100m por enzimoimunoanálise em indivíduos normais (sem risco aterogênico) e pacientes de alto risco e, estabelecer sua correlação com os fatores de risco aterogênico já estabelecidos por um estudo Observacional Transversal. Foram obtidos valores médios mais elevados de IgM-ApoB100m no grupo de indivíduos normais. Os complexos imunes IgM-ApoB100 correlacionam negativamente com os fatores de risco aterogênicos clássicos (sexo masculino, idosos, dislipidemia, LDL-C aumentado e HDL-C diminuído).

Atherosclerosis is the most prevalent vascular disease, which motivates extensive research on its pathogenesis. Lipoproteins can be modified by acetylation and oxidation mechanisms, at the level of lipid components as protein, becoming atherogenic. Modified Apolipoprotein B100 (ApoB100m), play an active role in the development of atherosclerotic lesions in conjunction with other risk factors. These have the ability to produce immune response leading to antibody production and subsequent formation of immune complexes. The importance of antibodies against ApoB100m in atherogenesis is still unclear since, contradictory data exist on whether their role is protective or atherogenic. Two objectives were established: to determine the levels of circulating immune complexes IgM-ApoB100m by enzyme immunoassay, in normal subjects (without atherogenic risk) and high-risk patients and to establish its correlation with atherogenic risk factors established by a cross-sectional study. Higher mean values of IgM-ApoB100m were obtained in the group of normal subjects. Immune complexes IgM-ApoB100 negatively correlated with classic atherogenic risk factors (male, older, dyslipidemia, increased LDL-C and decreased HDL-C).

La aterosclerosis es la patología vascular de mayor prevalencia, lo cual motiva numerosas investigaciones sobre su fisiopatogenia. Las lipoproteínas pueden ser modificadas por mecanismos de oxidación y acetilación entre otros, a nivel de sus componentes lipídicos como proteicos, tornándose aterogénicas. Las Apolipoproteínas B100 modificadas (ApoB100m), desempeñan un rol activo en el desarrollo de las lesiones ateroscleróticas conjuntamente con otros factores de riesgo. Éstas tienen la capacidad de producir respuesta inmune llevando a la producción de anticuerpos y la subsecuente formación de complejos inmunes. La importancia de los anticuerpos contra las ApoB100m en la aterogénesis todavía no está clara, existiendo datos contradictorios respecto a si su rol es protectivo o aterogénico. Se establecieron dos objetivos: Determinar los niveles de complejos inmunes circulantes IgM-ApoB100m por enzimoinmunoanálisis, en sujetos normales (sin riesgo aterogénico) y pacientes con alto riesgo y establecer su correlación con los factores de riesgo aterogénico ya establecidos, mediante un estudio observacional transversal. Se obtuvieron valores medios más elevados de IgM-ApoB100m en el grupo de sujetos normales. Los complejos inmunes IgM-ApoB100m correlacionan negativamente con los factores de riesgo aterogénicos clásicos (sexo masculino, avanzada edad, dislipemia, LDL-C aumentado y HDL-C disminuido).

Resumo Introdução: Foi postulada uma ligação entre psoríase e aterosclerose subclínica. A rede de citocinas pode intermediar essa associação. Poucos dados estão disponíveis em pacientes com psoríase leve. Avaliamos a espessura íntima-média carotídea (cIMT) em psoriáticos e controles livres de medicação. Paralelamente, pesquisamos a associação de cIMT com os índices de atividade de doença e interleucinas séricas (IL) em pacientes com psoríase. Método: Um radiologista experiente procedeu à análise do cIMT. As concentrações de citocinas foram avaliadas por citometria de fluxo. A atividade da doença foi avaliada pelo índice de gravidade (PASI) e pela área de superfície corporal (BSA). Resultados: Sessenta e cinco (65) pacientes e 64 controles foram estudados. A idade média dos pacientes (50,9 anos) não diferiu dos controles (p=0,362). PASI e BSA baixos (< 10) prevaleceram (69,2% e 56,9%, respectivamente). As medianas de IL-12p70, TNF-α, IL-1β e IL-10 foram significativamente menores nos casos do que nos controles (p<0,05 ajustado), enquanto as medianas de IL-6 e IL-8 não diferiram nos grupos (p>0,05 ajustado). Tabagismo e diabetes mellitus predominaram nos casos (p=0,002). Um cIMT alterado (≥ 0,9 mm) foi mais frequente nos casos do que nos controles (23,8% versus 8,5%, p=0,045 ajustado). A média de cIMT foi maior nos casos com significância borderline (p=0,057). Os escores de cIMT não se correlacionaram com o PASI (rs=0,066; p=0,250) ou o BSA (rs=0,175; p=0,185), mas se correlacionaram significativamente com a IL-6 sérica (rs=0,26; p=0,005). Conclusão: A aterosclerose subclínica foi mais frequente em pacientes com psoríase leve do que nos controles. Em psoriáticos, cIMT correlacionou-se com níveis de IL-6 no soro, apontando para um eventual papel pró-aterogênico para a IL-6 nesses pacientes. Novos estudos devem esclarecer a ligação da aterogênese com citocinas na psoríase.

Summary Introduction: A link of psoriasis with subclinical atherosclerosis has been postulated and cytokine network might intermediate this association. Few data are available in patients with mild psoriasis. We evaluated carotid intima-media thickness (cIMT) in drug-free psoriatic individuals and controls. In parallel, we searched for associations of cIMT with disease activity indexes and serum interleukins (IL) in psoriatic patients. Method: An experienced radiologist performed the cIMT analyses. Cytokine concentrations were assessed by flow cytometry. Disease activity was evaluated based on psoriasis area and severity index (PASI) as well as body surface area (BSA). Results: Sixty-five (65) patients and 64 controls were studied. Mean age of patients (50.9 years) did not differ from controls (p=0.362). A low PASI and BSA (< 10) prevailed (69.2% and 56.9%, respectively). Median levels of IL-12p70, TNF-α, IL-1β and IL-10 were significantly lower in cases than in controls (adjusted p<0.05), while IL-6 and IL-8 medians did not differ between groups (adjusted p>0.05). Smoking habit and diabetes mellitus predominated in cases (p=0.002). An altered cIMT (≥ 0.9 mm) was more frequent in cases than in controls (23.8% versus 8.5%, adjusted p=0.045). Mean cIMT was higher in cases with a borderline significance (p=0.057). cIMT scores did not correlate to PASI (rs=0.066; p=0.250) or BSA (rs=0.175; p=0.185), but did correlate significantly with serum IL-6 (rs=0.26; p=0.005). Conclusion: Subclinical atherosclerosis was more frequent in patients with mild psoriasis than controls. cIMT in psoriatic individuals correlated with serum IL-6, pointing to an eventual proatherogenic role of IL-6 in these patients. Newer studies should clarify the connection of atherogenesis with cytokines in psoriasis.