Detection of subclinical atherosclerosis using vascular ultrasound as a vascular risk assessment method. Simplified protocol. / Detección de aterosclerosis subclínica mediante ecografía vascular como método de evaluación de riesgo vascular. Protocolo simplificado.

Cardiovascular disease secondary to atherosclerosis is the main cause of morbidity and mortality in the world. Cardiovascular risk stratification has proven to be an insufficient approach to detect those subjects who are going to suffer a cardiovascular event, which is why for years other markers have been sought to help stratify each individual with greater precision. Two-dimensional vascular ultrasound is a excellent method for vascular risk assessment.

Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity / Evaluación de la relación entre aterosclerosis e infección por Helicobacter pylori con medición del factor de diferenciación de crecimiento 15 e indicadores de aterosclerosis en adultos sin comorbilidad

Background The aim of this study was to investigate presence of subclinical atherosclerosis by measuring carotid intima-media thickness (CIMT) in patients with Helicobacter pylori (HP) and to assess effects of HP on atherosclerosis by evaluating markers of atherosclerosis and blood growth differentiation factor (GDF-15) levels. Materials and methods This cross-sectional study included 59 patients without comorbid disease who had HP and 30 healthy controls without HP in upper endoscopic biopsy. In order to assess atherosclerosis, the CIMT measurement was performed by sonography. Serum GDF-15 level was measured by ELISA method. In all patients, atherosclerosis markers were recorded. Atherogenic indices were calculated, including Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), plasma atherogenic index (PAI; log TG/HDL-c), non-HDL-c (TH-HDL-c) and atherogenic coefficient (AC; non-HDL-HDL-c). Results The GDF-15 level and CIMT were significantly higher in HP-positive group when compared to HP-negative group (p≤0.001). There was a significant correlation between serum GDF-15 level and CIMT (r=0.445; p≤0.001). There was no correlation between other atherosclerosis markers and serum GDF-15 level or CIMT. The bacterial intensity on endoscopic specimen was only correlated with CIMT (p<0.001). Vitamin B12 and D levels were comparable among groups. Conclusion This study suggested that there was a correlation between GDF-15 level and subclinical atherosclerosis development in patients with HP. However, GDF-15 level, which was found to be elevated while atherogenic indices were normal, can be an earlier marker for subclinical atherosclerosis. (AU)

Antecedentes El objetivo de este estudio fue investigar la presencia de aterosclerosis subclínica mediante la medición del grosor íntima-media de la carótida (GIMC) en pacientes con Helicobacter pylori y evaluar los efectos de H.pylori sobre la aterosclerosis mediante la evaluación de marcadores de aterosclerosis y de niveles de factor de diferenciación del crecimiento sanguíneo (growth differentiation factor 15 [GDF-15]). Materiales y métodos Este estudio transversal incluyó 59 pacientes sin enfermedad comórbida que tenían H.pylori y 30 controles sanos sin H.pylori en la biopsia endoscópica superior. Para evaluar la aterosclerosis, la medición de GIMC se realizó mediante ecografía. El nivel de GDF-15 en suero se midió mediante el método ELISA. En todos los pacientes se registraron marcadores de aterosclerosis. Se calcularon los índices aterogénicos, incluyendo el índice de riesgo de Castelli I y II (TG/cHDL y cLDL-cHDL, respectivamente), el índice aterogénico plasmático (PAI; log TG/HDL-c), no-cHDL (TH-cHDL) y el coeficiente aterogénico (no-HDL-cHDL). Resultados Los niveles de GDF-15 y de GIMC fueron significativamente más altos en el grupo H.pylori positivo en comparación con el grupo H.pylori negativo (p≤0,001). Hubo una fuerte correlación entre el nivel sérico de GDF-15 y el GIMC (r=0,445; p≤0,001). No hubo correlación entre otros marcadores de aterosclerosis y el nivel sérico de GDF-15 o GIMC. La intensidad bacteriana en la muestra endoscópica solo se correlacionó con GIMC (p≤0,001). Los niveles de vitaminaB12 y de vitaminaD fueron comparables entre los grupos. Conclusión Este estudio sugirió que había una correlación entre el nivel de GDF-15 y el desarrollo de aterosclerosis subclínica en pacientes con H.pylori. Sin embargo, el nivel de GDF-15, que se encontró elevado mientras que los índices aterogénicos eran normales, puede ser un marcador temprano de aterosclerosis subclínica. (AU)

Ultrasound screening for abdominal aortic aneurysm in primary care. / Utilidad de la ecografía en el cribado del aneurisma de aorta abdominal en atención primaria.

INTRODUCTION: Abdominal aortic aneurysm (AAA) constitutes a pathology with high mortality. There is currently no screening program implemented in primary care in Spain. OBJECTIVES: To evaluate the usefulness of ultrasound in the detection of AAA in the at-risk population in primary care. Secondarily, to identify subjects whose vascular risk (VR) should be reclassified and to determine whether AAA is associated with the presence of carotid plaque and other risk factors. MATERIAL AND METHODS: Cross-sectional, descriptive, multicenter, national, descriptive study in primary care. SUBJECTS: A consecutive selection of hypertensive males aged between 65 and 75 who are either smokers or former smokers, or individuals over the age of 50 of both sexes with a family history of AAA. MEASUREMENTS: Diameter of abdominal aorta and iliac arteries; detection of abdominal aortic and carotid atherosclerotic plaque. VR was calculated at the beginning and after testing (SCORE). RESULTS: One hundred and fifty patients were analyzed (age: 68.3±5 years; 89.3% male). Baseline RV was high/very high in 55.3%. AAA was detected in 12 patients (8%; 95% CI: 4-12); aortic ectasia in 13 (8.7%); abdominal aortic plaque in 44% and carotid plaque in 62% of the participants. VR was reclassified in 50% of subjects. The detection of AAA or ectasia was associated with the presence of carotid plaque, current smoking and lipoprotein(a), p<0.01. CONCLUSIONS: The prevalence of AAA in patients with VR is high. Ultrasound in primary care allows detection of AAA and subclinical atherosclerosis and consequently reclassification of the VR, demonstrating its utility in screening for AAA in the at-risk population.

Lysyl oxidase expression in smooth muscle cells determines the level of intima calcification in hypercholesterolemia-induced atherosclerosis. / La expresión de la lisil oxidasa en las células musculares lisas determina el nivel de calcificación de la íntima en la aterosclerosis inducida por hipercolesterolemia.

INTRODUCTION: Cardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve. METHODS: Immunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOXCMLV). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9D374Y) combined with an atherogenic diet. RESULTS: LOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6J) animals transduced with PCSK9D374Y and in the aortic root of ApoE-/- mice. In TgLOXCMLV mice, PCSK9D374Y transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX. CONCLUSIONS: Our results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.

Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients.

BACKGROUND AND AIMS: Neuregulin 1 (NRG-1) is one of the members of the epidermal growth factors proteins. The present study provides novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in type 2 diabetes (T2D). METHODS: The study included 50 patients with T2D and 40 healthy age- and gender-matched controls. Serum NRG-1 was measured using ELISA. Glycemic parameters, lipid profile and insulin resistance were assessed. Trans-thoracic echocardiography and carotid intima media thickness (CIMT) were studied for all study subjects. RESULTS: T2D patients had significantly lower serum NRG-1 levels than controls. Serum NRG-1 was negatively correlated with age, fasting blood glucose, HbA1c, insulin resistance, blood urea, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT. Regarding echocardiographic variables, serum NRG-1 was found to correlate positively with left ventricular global longitudinal strain and negatively with E/Ea ratio. NRG-1 was found to predict subclinical atherosclerosis in type 2 diabetes patients at a cut-off value<108.5pg/ml with 78% sensitivity and 80% specificity. CONCLUSIONS: A robust relationship was found between serum NRG-1 levels and hyperglycemia, insulin resistance, subclinical atherosclerosis, and cardiac dysfunction in patients with type 2 diabetes. These results shed light on a possible role of NRG-1 as a potential noninvasive biomarker for detection of cardiometabolic risk in T2D.

Update of HDL in atherosclerotic cardiovascular disease / Nuevos conceptos de las HDL en la enfermedad cardiovascular aterosclerótica

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the “HDL quality over quantity” hypothesis. The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors. (AU)

Estudios epidemiológicos respaldan una asociación inversa entre los niveles de colesterol de lipoproteínas de alta densidad (c-HDL) y la enfermedad cardiovascular aterosclerótica (ECVA), identificando el c-HDL como un importante factor de riesgo cardiovascular y postulando diversas funciones vasculares y cardioprotectoras de las HDL más allá de su capacidad para promover el transporte reverso del colesterol. Sin embargo, el fracaso de varios ensayos clínicos dirigidos a aumentar el c-HDL en pacientes con enfermedad cardiovascular manifiesta, puso en duda el concepto que incrementar la carga de c-HDL fuera una estrategia eficaz para potenciar sus propiedades protectoras. Paralelamente, numerosos estudios han evidenciado que las HDL son partículas complejas y heterogéneas cuya composición es esencial para mantener sus funciones protectoras, lo que refuerza la hipótesis de que «la calidad de las HDL prima sobre la cantidad». En el siguiente manuscrito revisamos el estado del arte sobre los últimos avances en torno a las funciones de las HDL en la ECVA, nos adentramos en los avances recientes en la comprensión de la complejidad de la composición de las partículas de HDL, incluidas las proteínas, los lípidos y otros componentes transportados por las HDL, y revisamos los resultados clínicos tras la administración de inductores del c-HDL, especialmente los inhibidores de la proteína transportadora del colesterol esterificado (CETP). (AU)

Enfermedad arterial periférica en población trabajadora: factores de riesgo y estilo de vida

Introducción: La Enfermedad Arterial Periférica (EAP) es definida como la oclusión de las arterias de las extremidades, se reconoce como la tercera causa de morbilidad vascular aterosclerótica, después del infarto agudo de miocardio y el accidente cerebrovascular. Aunque las enfermedades cardiovasculares se han relacionado con la ocupación, la información sobre la relación entre el trabajo con la EAP es escasa. Objetivo: Identificar la prevalencia de EAP en población laboralmente activa y su relación con variables sociodemográficas, clínicas y estilo de vida. Metodología: Se realizó un estudio analítico de tipo transversal, en 203 sujetos de 40 años o más, laboralmente activos de Popayán. Tras la firma del consentimiento, se realizó una entrevista, y se registraron las variables sociodemográficas y clínicas. Para el tamizaje de EAP se evaluó el índice tobillo brazo (ITB). Los participantes se clasificaron en categorías basadas en el ITB de la siguiente manera: EAP ≤ 0,90; 0,91 a 0,99 normal; y no compresible > 1,40. Los datos fueron analizados con el programa SPSS versión 26.0, se aplicó la prueba de Kolmogorov-Smirnov como prueba de normalidad, la t Student para evaluar diferencias de medias entre los grupos de estudio y la prueba de Chi-cuadrado. Resultados y discusión: La prevalencia fue del 2,5 % para EAP, siendo el primer estudio reportado para población trabajadora en Colombia. La EAP fue más prevalente en empleados manuales (2,8 %) e ingresos bajos (30 %); además, fueron obesos y fumadores. El riesgo encontrado para edad fue OR 1,5; IC95 % 1,17 a 2,14, género OR 1,2; IC95 % 1,20 a 3,28 y DM2 OR 1,5; IC95 % 1,23 a 6,68. Conclusión: Se estableció por primera vez la prevalencia de EAP (2,5 %) en una población laboralmente activa de Popayán, siendo más prevalente en los individuos con ingresos bajos, expuestos a factores de riesgo cardiovascular y con antecedente familiar de DM2.

Introduction: The Peripheral Arterial Disease (PAD) is defined as the occlusion of the extremities' arteries, and it is known to be the third vascular atherosclerotic cause of death after acute myocardial infarction and brain stroke. Even though cardiovascular diseases had been linked to occupation, information about the relation between PAD and labor activity runs short. Objective: To identify the PAD prevalence in the working population and its relationship with sociodemographic, clinical and lifestyle variables. Methodology: A cross-sectional analytical study was conducted in 203 people of >40 years, actively working in the city of Popayán. After consent signing, interviews were completed to record such variables. PAD testing was evaluated through Ankle-Brachial Index (ABI). Participants were grouped into categories based on ABI as follows: PAD ≤0.90; normal 0.91 to 0.99; and non-compressible >1.40. Collected data was analyzed in SPSS version 26.0, applying Kolmogorov-Smirnov test as the normal; t Student test to evaluate mean differences between study groups and Chi-square. Results and discussion: PAD prevalence was 2.5 % being the very first report done for Colombia's working class. PAD was prevalent for manual-labor employees (2.8 %), low-income people (30 %), adding obesity and smoking to their profile. Age risk found was (OR 1.5; IC 95 % 1.17 to 2.14), by gender (OR 1.2; IC 95 % 1.20 to 3.28); DM2 (OR 1.5; IC 95 % 1.23 to 6.68). Conclusion: It was determined for the first time a prevalence of (2.5 °%) PAD for a population actively working in Popayán, being more frequent with individuals with low income, people exposed to higher cardiovascular risks, and for people with family DM2 records.

Influencia del estrés oxidativo en la evolución de la aterosclerosis carotídea / Influence of oxidative stress on the progression of carotid atherosclerosis

Introducción y objetivo: el estrés oxidativo (EO) ha demostrado clara influencia en el desarrollo de las placas de ateroma por daños provocados en endotelio vascular. El objetivo de este trabajo es realizar un estudio de los principales marcadores de estrés oxidativo en pacientes con enfermedad aterosclerótica de la arteria carótida como signo de vulnerabilidad, analizar la implicación de la situación redox y el estado metabólico mitocondrial en patología aterosclerótica de la arteria carótida y su relación con clínica neurológica. Pacientes y métodos: se estudiaron las placas de ateroma obtenidas de pacientes intervenidos de endarectomía carotídea (asintomáticos y sintomáticos) en el Servicio de Angiología del Hospital Clínico Universitario de Valladolid en el año 2020. Se recogieron variables clínicas y demográficas y la existencia de sintomatología neurológica. Las características anatómicas y hemodinámicas se estudiaron mediante estudio eco Doppler y angiografía mediante tomografía computarizada en el preoperatorio. Se analizaron placas de ateroma como estimadores del grado de peroxidación lipídica que reflejaron el estado redox. Se ha estimado un tamaño muestral de 45 muestras en cada grupo, con una tasa de pérdidas de seguimiento del 5 %. Se estudiaron las diferencias entre los grupos mediante χ2 y la t de Student para determinar relación entre el potencial redox con las características morfológicas de placa de ateroma. Se utilizó el programa estadístico SPSS 27.0, aceptando como significativo un valor p < 0,05. Resultados: las placas de ateroma calcificadas mostraron mayor capacidad antioxidante con respecto a las placas de ateroma no calcificadas en el parámetro ABTS: 2,2-ácino-bis(ácido 3-etilbenzotiazolina-6-sulfónico) (2635,08 frente a 2803,28). La relación es estadísticamente significativa (p = 0,007)...(AU)

Introduction and objective: oxidative Stress (OS) has proven to have a clear impact on the development of atherosclerotic plaques due to the damage it causes to vascular endothelium. The aim of this study is to conduct a research on key oxidative stress markers in patients with carotid artery atherosclerotic disease as a sign of vulnerability, analyze the implications of the redox status and mitochondrial metabolic state in carotid artery atherosclerotic disease, and its relationship with neurological clinical presentation. Patients and methods: atherosclerotic plaques obtained from carotid endarterectomy patients (both asymptomatic and symptomatic) performed the Department of Angiology, Vascular and Endovascular Surgery of Hospital Clinico Universitario de Valladolid, Spain in 2020 will be examined. The clinical-demographic variables and the presence of neurological symptoms will be recorded. Anatomical and hemodynamic characteristics will be studied using Doppler ultrasound and coronary computed tomography angiography (CCTA) preoperatively. Atherosclerotic plaques will be analyzed as estimators of the degree of lipid peroxidation showing the redox state. A sample size of 45 speciments from each group has been estimated with a loss to follow-up rate of 5 %. Inter-group differences will be studied using the chi-square and Student’s t tests to establish the relationship between redox potential and morphological characteristics of the atheromatous plaque. SPSS 27.0 statistical software will be used, with a significance level set at p < 0.05. Results: calcified atherosclerotic plaques showed higher antioxidant capacity compared to non-calcified plaques in the ABTS parameter (2,2-azino-bis(3-ethylbenzthioziozline-6-sulfonic)) (2635.08 vs 2803.28), with statistically significant relationship (p = 0.007). They also exhibited greater antioxidant defense when analyzing catalase activity (160.73 vs 175.13) and SOD activity (1.11 vs 1.49) (p = 0.049)...(AU)

Update of HDL in atherosclerotic cardiovascular disease.

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the "HDL quality over quantity" hypothesis. The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors.

[Coronary lithotripsy in calcified lesions: fragmented calcium]. / Litotricia coronaria en lesiones calcificadas: fragmentando el calcio.

Background: Complex calcified coronary lesions are a frequent finding during percutaneous coronary intervention, representing for decades a challenge and limitation in patients with indication of revascularization, due to suboptimal angiographic results, high incidence of perioperative complications and long-term adverse events despite the multiple strategies employed, such as the use of cutting balloon, high-pressure balloons or rotational or orbital atherectomy, interventions with limitations that have hindered its routine use, recently a new plaque modification technique known as coronary intravascular lithotripsy has burst into the treatment of this complex entity, which consists in the use of a specially modified balloon for the emission of pulsatile mechanical energy (sonic pressure waves) that allows modifying the calcified plate. Clinical case: By presenting a series of clinical cases and reviewing the literature, our initial experience is presented, key elements are summarized and discussed in the understanding of this new intervention technique necessary for decision making. Conclusion: Coronary intravascular lithotripsy is projected as a promising technique for the modification and preparation of superficial and deep calcified coronary lesions, through microfractures that allow the apposition and effective expansion of the stent, strategy that according to different trials (Disrupt CAD series, SOLSTICE assay) and records presents a high efficiency and good safety profile, data consistent with our initial experience.

Introducción: las lesiones coronarias calcificadas complejas son un hallazgo frecuente durante el intervencionismo coronario percutáneo, han representado durante décadas un desafío y limitante en pacientes con indicación de revascularización, debido a resultados angiográficos subóptimos, alta incidencia de complicaciones perioperatorias y eventos adversos a largo plazo a pesar de las múltiples estrategias empleadas, como el uso de balones de corte, balones de alta presión o la aterectomía rotacional u orbital, intervenciones con limitantes que han dificultado su uso rutinario. Recientemente, una nueva técnica de modificación de placa conocida como litotricia intravascular coronaria ha irrumpido en el tratamiento de esta compleja entidad, la cual consiste en la utilización de un balón especialmente modificado para la emisión de energía mecánica pulsátil (ondas de presión sónicas) que permite modificar la placa calcificada. Caso clínico: mediante la presentación de una serie de casos clínico y revisión de literatura se presenta nuestra experiencia inicial, se resume y discuten elementos claves en el entendimiento de esta nueva técnica de intervencionismo necesarios para la toma de decisiones. Conclusión: la litotricia intravascular coronaria se proyecta como una técnica prometedora para la modificación y preparación de lesiones coronarias calcificadas superficiales y profundas, mediante microfracturas que permiten la aposición y expansión efectiva del stent; estrategia que de acuerdo con diferentes ensayos (serie Disrupt CAD, ensayo SOLSTICE) y registros presenta una eficacia alta y buen perfil de seguridad, datos concordantes con nuestra experiencia inicial.

Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity.

BACKGROUND: The aim of this study was to investigate presence of subclinical atherosclerosis by measuring carotid intima-media thickness (CIMT) in patients with Helicobacter pylori (HP) and to assess effects of HP on atherosclerosis by evaluating markers of atherosclerosis and blood growth differentiation factor (GDF-15) levels. MATERIALS AND METHODS: This cross-sectional study included 59 patients without comorbid disease who had HP and 30 healthy controls without HP in upper endoscopic biopsy. In order to assess atherosclerosis, the CIMT measurement was performed by sonography. Serum GDF-15 level was measured by ELISA method. In all patients, atherosclerosis markers were recorded. Atherogenic indices were calculated, including Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), plasma atherogenic index (PAI; log TG/HDL-c), non-HDL-c (TH-HDL-c) and atherogenic coefficient (AC; non-HDL-HDL-c). RESULTS: The GDF-15 level and CIMT were significantly higher in HP-positive group when compared to HP-negative group (p≤0.001). There was a significant correlation between serum GDF-15 level and CIMT (r=0.445; p≤0.001). There was no correlation between other atherosclerosis markers and serum GDF-15 level or CIMT. The bacterial intensity on endoscopic specimen was only correlated with CIMT (p<0.001). Vitamin B12 and D levels were comparable among groups. CONCLUSION: This study suggested that there was a correlation between GDF-15 level and subclinical atherosclerosis development in patients with HP. However, GDF-15 level, which was found to be elevated while atherogenic indices were normal, can be an earlier marker for subclinical atherosclerosis.

Effect of low-sodium salt applied to Chinese modified DASH diet on arterial stiffness in older patients with hypertension and type 2 diabetes / Efecto de una sal baja en sodio aplicada a la dieta china DASH modificada sobre la rigidez arterial en pacientes mayores con hipertensión y diabetes tipo 2

Background and purpose: the Dietary Approaches to Stop Hypertension (DASH) diet has multifunctional health benefits. We evaluated theeffects of low-sodium salt applied to Chinese modified DASH diet on arterial stiffness in older patients with hypertension and type 2 diabetes.Methods: sixty-one older adults with hypertension and type 2 diabetes were randomly allocated to low sodium salt group (n = 31) or normalsodium salt group (n = 30). They were given the Chinese modified DASH diet plus low-sodium salt (52 % sodium chloride) or same diet plusregular salt (99 % sodium chloride) for eight weeks, respectively. Brachial and ankle pulse wave conduction velocity, ankle brachial index andatherosclerosis-related indices were measured at baseline and week 8. In addition, 24-hour urine and blood samples were measured at baseline,the 4th week and the end of the intervention.Results: as compared with the baseline, the low sodium salt group significantly decreased in ankle brachial index (-0.09 ± 0.11, p < 0.001)and brachial and ankle pulse wave conduction velocity (-133.07 ± 265.99 cm/s, p = 0.010) at week 8 while the normal sodium salt group onlydecreased significantly in ankle brachial index (-0.06 ± 0.12, p = 0.010) at week 8.Conclusion: the low-sodium salt applied to Chinese modified DASH diet may improve arterial stiffness in patients with hypertension and type 2diabetes. Further research with an extended follow-up is needed. (AU)

Antecedentes y propósito: la dieta DASH (del inglés Dietary Approaches to Stop Hypertension) tiene beneficios multifuncionales para la salud.Evaluamos los efectos de una sal baja en sodio aplicada a la versión modificada china de la dieta DASH sobre la rigidez arterial en pacientesmayores con hipertensión y diabetes tipo 2.Métodos: sesenta y un adultos mayores con hipertensión arterial y diabetes tipo 2 fueron asignados al azar al grupo de sal baja en sodio (n= 31) o al grupo de sal con contenido normal de sodio (n = 30). Se les administró la versión china modificada de la dieta DASH más sal bajaen sodio (52 % de cloruro de sodio) o la misma dieta más sal con la cantidad normal de sodio (99 % cloruro de sodio) durante ocho semanas,respectivamente. Se midieron la velocidad de onda de pulso brazo-tobillo, el índice brazo-tobillo y los índices relacionados con la aterosclerosis alinicio del estudio y a la semana 8. Se recogieron muestras de orina y sangre de 24 horas al inicio, a la cuarta semana y al final de la intervención.Resultados: en comparación con el estado inicial, el grupo de sal baja en sodio disminuyó significativamente el índice brazo-tobillo (-0,09 ±0,11, p < 0,001) y la velocidad de onda de pulso brazo-tobillo (-133,07 ± 265,99 cm/s, p = 0,010) en la semana 8, mientras que el grupode sal con contenido normal de sodio solo disminuyó significativamente en el índice brazo-tobillo (-0,06 ± 0,12, p = 0,010) en la semana 8.Conclusión: la sal baja en sodio aplicada a la versión china modificada de la dieta DASH puede mejorar la rigidez arterial en pacientes conhipertensión y diabetes tipo 2. Se necesitan más investigaciones con un seguimiento prolongado. (AU)

Effect of low-sodium salt applied to Chinese modified DASH diet on arterial stiffness in older patients with hypertension and type 2 diabetes.

Introduction: Background and purpose: the Dietary Approaches to Stop Hypertension (DASH) diet has multifunctional health benefits. We evaluated the effects of low-sodium salt applied to Chinese modified DASH diet on arterial stiffness in older patients with hypertension and type 2 diabetes. Methods: sixty-one older adults with hypertension and type 2 diabetes were randomly allocated to low sodium salt group (n = 31) or normal sodium salt group (n = 30). They were given the Chinese modified DASH diet plus low-sodium salt (52 % sodium chloride) or same diet plus regular salt (99 % sodium chloride) for eight weeks, respectively. Brachial and ankle pulse wave conduction velocity, ankle brachial index and atherosclerosis-related indices were measured at baseline and week 8. In addition, 24-hour urine and blood samples were measured at baseline, the 4th week and the end of the intervention. Results: as compared with the baseline, the low sodium salt group significantly decreased in ankle brachial index (-0.09 ± 0.11, p < 0.001) and brachial and ankle pulse wave conduction velocity (-133.07 ± 265.99 cm/s, p = 0.010) at week 8 while the normal sodium salt group only decreased significantly in ankle brachial index (-0.06 ± 0.12, p = 0.010) at week 8. Conclusion: the low-sodium salt applied to Chinese modified DASH diet may improve arterial stiffness in patients with hypertension and type 2 diabetes. Further research with an extended follow-up is needed.

Introducción: Antecedentes y propósito: la dieta DASH (del inglés Dietary Approaches to Stop Hypertension) tiene beneficios multifuncionales para la salud. Evaluamos los efectos de una sal baja en sodio aplicada a la versión modificada china de la dieta DASH sobre la rigidez arterial en pacientes mayores con hipertensión y diabetes tipo 2. Métodos: sesenta y un adultos mayores con hipertensión arterial y diabetes tipo 2 fueron asignados al azar al grupo de sal baja en sodio (n = 31) o al grupo de sal con contenido normal de sodio (n = 30). Se les administró la versión china modificada de la dieta DASH más sal baja en sodio (52 % de cloruro de sodio) o la misma dieta más sal con la cantidad normal de sodio (99 % cloruro de sodio) durante ocho semanas, respectivamente. Se midieron la velocidad de onda de pulso brazo-tobillo, el índice brazo-tobillo y los índices relacionados con la aterosclerosis al inicio del estudio y a la semana 8. Se recogieron muestras de orina y sangre de 24 horas al inicio, a la cuarta semana y al final de la intervención. Resultados: en comparación con el estado inicial, el grupo de sal baja en sodio disminuyó significativamente el índice brazo-tobillo (-0,09 ± 0,11, p < 0,001) y la velocidad de onda de pulso brazo-tobillo (-133,07 ± 265,99 cm/s, p = 0,010) en la semana 8, mientras que el grupo de sal con contenido normal de sodio solo disminuyó significativamente en el índice brazo-tobillo (-0,06 ± 0,12, p = 0,010) en la semana 8. Conclusión: la sal baja en sodio aplicada a la versión china modificada de la dieta DASH puede mejorar la rigidez arterial en pacientes con hipertensión y diabetes tipo 2. Se necesitan más investigaciones con un seguimiento prolongado.

Nanotransportadores activos de cannabinoides para el tratamiento de la aterosclerosis / Active cannabinoid nanocarriers for the treatment of atherosclerosis

Con la intención de vehiculizar fármacos cannabinoides (agonistas CB2) de forma selectiva hacia la placa de ateroma, se han obtenido nanopartículas biocompatibles y biodegradables. Para ello, las nanopartículas PEGyladas, han sido funcionalizadas con un péptido capaz de unirse selectivamente a proteínas endoteliales de adhesión sobreexpresadas en la placa aterosclerótica (vascular cell adhesion molecule 1, VCAM-1). Las partículas han sido caracterizadas fisicoquímicamente, in vitro en cultivos celulares e in vivo en un modelo animal de aterosclerosis (ratones deficientes en apolipoproteína E, ApoE-/-), demostrando un óptimo control espacio-temporal de la liberación del cannabinoide y una respuesta farmacológica superior. Dado que los fármacos agonistas CB2 presentan alta lipofilia y baja disponibilidad, la introducción de nanosistemas selectivos para la vehiculización de estos fármacos antiaterogénicos, mejoraría su biodisponibilidad y eficacia.El trabajo presentado muestra parte de los resultados obtenidos de un proyecto previo. Estos resultados nos han avalado para la concesión de una nueva ayuda de financiación para abordar una estrategia más avanzada que implica la introducción de elementos de diagnóstico y de un fitocannabinoide. (AU)

In order to selectively deliver cannabinoid drugs (CB2 agonists) to the atherosclerotic plaque, biocompatible and biodegradable nanoparticles have been obtained. For this purpose, the PEGylated nanoparticles have been functionalized with a peptide capable of selectively binding to endothelial adhesion proteins overexpressed in the atherosclerotic plaque (vascular cell adhesion molecules 1, VCAM-1). The particles have been characterized physicochemically, in vitro in cell cultures and in vivo in an animal model of atherosclerosis (apolipoprotein E-deficient ApoE-/- mice), demonstrating optimal spatiotemporal control of cannabinoid release and superior pharmacological response. Given that CB2 agonist drugs present high lipophilicity and low availability, the introduction of selective nanosystems for the vehiculation of these antiatherogenic drugs would improve their bioavailability and efficacy.The work presented shows part of the results obtained from a previous project. These results have supported us for the award of a new funding grant to address a more advanced strategy involving the introduction of diagnostic elements and a phytocannabinoid. (AU)

Satisfacción de los empleadores con el desempeño de egresados de la maestría "Investigación en aterosclerosis" / Employers' Satisfaction with the Performance of Graduates from a Master's Program about Research in Atherosclerosis

Introducción: Los estudios de empleadores cobran cada vez mayor importancia en el ámbito de la educación superior, a partir de la necesidad institucional de evaluar la pertinencia de sus programas e identificar expectativas de crecimiento, al permitir conocer la existencia de vinculación institucional y desarrollo de sus egresados. Objetivo: Describir la satisfacción de los empleadores con el desempeño de egresados de la décima edición de la maestría investigación en aterosclerosis. Métodos: Se hizo un estudio descriptivo de corte transversal. Se seleccionaron los empleadores de los egresados de la última edición terminada. Se les aplicó una encuesta de forma autoadministrada para explorar la satisfacción con el desempeño de los egresados de la maestría. Resultados: El total de los empleadores manifestaron que la maestría respondía a las necesidades asistenciales, docentes e investigativas del centro en el que laboraba el máster; que este aplicaba creativa y críticamente en su práctica diaria los conocimientos adquiridos en el programa de maestría; y que era capaz de diseñar y dirigir proyectos de investigación. El 94,1 por ciento respondió que, después de graduado de la maestría, el máster tenía la capacidad de diseñar y organizar cursos de superación para solucionar problemas de la institución. El 76,5 por ciento contestó que cumplía las expectativas y el 52,9 por ciento que se sentía satisfecho con el desempeño de los egresados. Conclusiones: Los empleadores manifestaron que los egresados satisfacían el perfil declarado en la maestría. Los egresados cumplieron con las expectativas de sus empleadores y los empleadores se encontraron satisfechos con el desempeño de los egresados(AU)

Introduction: Employer surveys are becoming increasingly important in the field of higher education, from the institutional need to evaluate the relevance of their programs and identify growth expectations, by allowing to know the existence of institutional linkage and the development of its graduates. Objective: To describe the satisfaction of employers with the performance of graduates from the tenth edition of a master's program about research in atherosclerosis. Methods: A descriptive and cross-sectional study was carried out. The employers of the graduates from the last completed edition were selected. A self-administered survey was conducted on them to explore satisfaction with the performance of the graduates from the master's program. Results: The whole number of employers stated that the master's degree responded to the care, teaching and research needs of the center where the master's degree holder worked; that he/she applied the knowledge acquired in the master's program creatively and critically in his/her daily practice; and hat he/she was capable of designing and directing research projects. 94.1 percent responded that, after graduating from the master's program, the master's degree holder had the capacity to design and organize professional improvement courses to solve the institutional problems. 76.5 percent answered that the master's degree met the expectations, while 52.9 percent responded that they were satisfied with the performance of the graduates. Conclusions: Employers stated that the graduates met the profile stated in the master's program. The graduates met the expectations of their employers, who were satisfied with the performance of the graduates(AU)

Importance of so called "novel cardiovascular risk factors" in severity of coronary artery calcification; how serious they should be taken: a systematic review and metaanalysis / Importancia de los denominados "factores novedosos de riesgo cardiovascular" en la severidad de la calcificación de las arterias coronarias; qué tan serios deben tomarse: una revisión sistemática y un metaanálisis

Abstract Cardiovascular diseases are among important causes of death. Atherosclerosis is an important etiology for coronary artery diseases in which coronary artery calcification plays a principal role. Recently novel cardiovascular risk factors in coronary calcification are under attention. In this study, we investigated possible association between novel cardiovascular risk factors and coronary calcification. This is a prospectively registered systematic review and meta-analysis in PROSPERO and was performed in accordance with PRISMA guidelines. Medical databases were searched. Primary papers were screened and studies reporting our outcomes of interest were selected for data extraction. Quantitative data syntheses were performed using Comprehensive Meta-analysis Ver.3. In this study, 5252 papers were screened and finally 28 papers including 31241 patients underwent data extraction. Based on our findings, neutrophil/lymphocyte ratio (8 out of 10), red cell distribution width (r = 0.250, p < 0.0001), and interleukin 6 (odds ratio [OR]: 1.101 [95% confidence interval (CI): 1.001-1.210], p = 0.047) were associated with severity of coronary calcification while C-reactive protein (one out of eight) was not associated with coronary calcification. Results of lymphocyte/monocyte ratio (r = -0.120, p < 0.001), platelet/lymphocyte ratio (OR: 1.47 [95% CI: 0.89-2.41, p = 0.124]), and MPV (r = 0.017, p = 0.814 vs. OR: 1.91 [95% CI: 1.28-2.85, p = 0.002]) remained controversial due to few number of included studies or contrary results. We can conclude that neutrophil/lymphocyte ratio, red cell distribution width, and interleukin-6 are significantly associated with coronary calcification and C-reactive protein is not significantly associated with severity of coronary calcification. Our results about mean platelet volume, platelet/lymphocyte ratio, and lymphocyte/monocyte ratio are not reliable and require further investigations.

Resumen Las enfermedades cardiovasculares se encuentran entre las primeras causas de mortalidad. La aterosclerosis es una etiología importante de las enfermedades de las arterias coronarias en la que la calcificación de las arterias coronarias juega un papel principal. Recientemente, se están prestando atención a factores novedosos de riesgo cardiovascular en la calcificación coronaria. En este estudio investigamos la asociación posible entre los factores novedosos de riesgo cardiovascular y la calcificación coronaria. Esta es una revisión sistemática y metaanálisis registrados de forma prospectiva en PROSPERO y se realizó de acuerdo con las pautas de PRISMA. Se realizaron búsquedas en bases de datos médicas. Se examinaron los artículos primarios y se seleccionaron para la extracción de datos los estudios cuyos resultados fueron de nuestro interés. Las síntesis de datos cuantitativos se realizaron utilizando Comprehensive Meta-analysis Ver.3. En este estudio se seleccionaron 5252 artículos y finalmente se extrajeron los datos de 28 artículos que incluían 31241 pacientes. Según nuestros hallazgos, la proporción de neutrófilos/linfocitos (8 de 10), el ancho de distribución de glóbulos rojos (r = 0,250, valor de p < 0.0001) y la interleucina 6 (OR: 1.101 [IC del 95%: 1.001-1.210], valor p = 0.047) se asociaron con la gravedad de la calcificación coronaria, mientras que la proteína C reactiva (1 de 8) no se asoció con la calcificación coronaria. Resultados de la proporción linfocitos/monocitos (r = -0,120, valor p < 0,001), la proporción plaquetas/linfocitos (OR: 1,47 [IC 95%: 0.89-2.41, valor p = 0.124]) y el volumen plaquetario medio (r = 0.017, valor p = 0.814 C. OR: 1.91 [IC 95%: 1.28-2.85, valor p = 0.002]) siguieron siendo polémicos debido al escaso número de estudios incluidos o resultados contrarios. Podemos concluir que la proporción de neutrófilos/linfocitos, el ancho de distribución de los glóbulos rojos y la interleucina 6 se asocian significativamente con la calcificación coronaria y la proteína C reactiva no se asocia significativamente con la gravedad de la calcificación coronaria. Nuestros resultados sobre el volumen plaquetario medio, la proporción de plaquetas/linfocitos y la proporción de linfocitos/monocitos no son confiables y requieren más investigaciones.

Clonal hematopoiesis and atherosclerotic cardiovascular disease: A primer / Hematopoyesis clonal y enfermedad aterosclerótica cardiovascular: un iniciador

Despite current standards of care, a considerable risk of atherosclerotic cardiovascular disease remains in both primary and secondary prevention. In this setting, clonal hematopoiesis driven by somatic mutations has recently emerged as a relatively common, potent and independent risk factor for atherosclerotic cardiovascular disease and other cardiovascular conditions. Experimental studies in mice suggest that mutations in TET2 and JAK2, which are among the most common in clonal hematopoiesis, increase inflammation and are causally connected to accelerated atherosclerosis development, which may explain the link between clonal hematopoiesis and increased cardiovascular risk. In this review, we provide an overview of our current understanding of this emerging cardiovascular risk factor.(AU)

A pesar de los estándares de los cuidados actuales, persiste un riesgo considerable de enfermedad cardiovascular aterosclerótica tanto en la prevención primaria como secundaria. En este contexto, la hematopoyesis clonal impulsada por mutaciones somáticas ha emergido recientemente como un factor de riesgo relativamente común, potente e independiente, para la enfermedad cardiovascular aterosclerótica y otras situaciones cardiovasculares. Los estudios experimentales en ratones sugieren que las mutaciones en TET2 y JAK2, que se encuentran dentro de las hematopoyesis clonales más comunes, incrementan la inflamación y están causalmente conectadas con el desarrollo de aterosclerosis acelerado, lo cual puede explicar el vínculo entre la hematopoyesis clonal y el incremento del riesgo cardiovascular. En esta revisión, aportamos una visión general de nuestra comprensión actual de este factor de riesgo cardiovascular.(AU)

Vascular smooth muscle cell aging: Insights from Hutchinson-Gilford progeria syndrome / Envejecimiento de las células del músculo liso vascular: conclusiones derivadas del síndrome de progeria de Hutchinson-Gilford

Vascular smooth muscle cells (VSMCs) constitute the principal cellular component of the medial layer of arteries and are responsible for vessel contraction and relaxation in response to blood flow. Alterations in VSMCs can hinder vascular system function, leading to vascular stiffness, calcification and atherosclerosis, which in turn may result in life-threatening complications. Pathological changes in VSMCs typically correlate with chronological age; however, there are certain conditions and diseases, such as Hutchinson-Gilford progeria syndrome (HGPS), that can accelerate this process, resulting in premature vascular aging. HGPS is a rare genetic disorder characterized by severe VSMC loss, accelerated atherosclerosis and death from myocardial infarction or stroke during the adolescence. Because experiments with mouse models have demonstrated that alterations in VSMCs are responsible for early atherosclerosis in HGPS, studies on this disease can provide insights into the mechanisms of vascular aging and assess the relative contribution of VSMCs to this process.(AU)

Las células del músculo liso vascular (CMLV) constituyen el principal componente celular de la capa medial arterial, siendo responsables de la contracción y relajación de los vasos en respuesta al flujo sanguíneo. Las alteraciones en CMLV dificultan la función vascular, generan rigidez vascular, calcificación y aterosclerosis, pudiendo resultar en complicaciones mortales. Cambios patológicos en CMLV suelen correlacionarse con la edad cronológica; sin embargo, existen afecciones y enfermedades, como el síndrome de progeria de Hutchinson-Gilford (HGPS), que pueden acelerar este proceso, provocando envejecimiento vascular prematuro. El HGPS es un trastorno genético raro caracterizado por una pérdida grave de CMLV, aterosclerosis acelerada y muerte por infarto de miocardio o ictus durante la adolescencia. Experimentos con modelos de ratón demostraron que las alteraciones en CMLV son responsables de la aterosclerosis temprana en HGPS. Por tanto, estudios sobre esta enfermedad pueden proporcionar información sobre los mecanismos del envejecimiento vascular y caracterizar la contribución de las CMLV.(AU)

Vascular smooth muscle cell aging: Insights from Hutchinson-Gilford progeria syndrome.

Vascular smooth muscle cells (VSMCs) constitute the principal cellular component of the medial layer of arteries and are responsible for vessel contraction and relaxation in response to blood flow. Alterations in VSMCs can hinder vascular system function, leading to vascular stiffness, calcification and atherosclerosis, which in turn may result in life-threatening complications. Pathological changes in VSMCs typically correlate with chronological age; however, there are certain conditions and diseases, such as Hutchinson-Gilford progeria syndrome (HGPS), that can accelerate this process, resulting in premature vascular aging. HGPS is a rare genetic disorder characterized by severe VSMC loss, accelerated atherosclerosis and death from myocardial infarction or stroke during the adolescence. Because experiments with mouse models have demonstrated that alterations in VSMCs are responsible for early atherosclerosis in HGPS, studies on this disease can provide insights into the mechanisms of vascular aging and assess the relative contribution of VSMCs to this process.

Clonal hematopoiesis and atherosclerotic cardiovascular disease: A primer.

Despite current standards of care, a considerable risk of atherosclerotic cardiovascular disease remains in both primary and secondary prevention. In this setting, clonal hematopoiesis driven by somatic mutations has recently emerged as a relatively common, potent and independent risk factor for atherosclerotic cardiovascular disease and other cardiovascular conditions. Experimental studies in mice suggest that mutations in TET2 and JAK2, which are among the most common in clonal hematopoiesis, increase inflammation and are causally connected to accelerated atherosclerosis development, which may explain the link between clonal hematopoiesis and increased cardiovascular risk. In this review, we provide an overview of our current understanding of this emerging cardiovascular risk factor.