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Resumen Introduccion La hipercolesterolemia familiar (HF) infantil esta infradiagnosticada y su diagnostico no es facil en la practica clinica. El objetivo fue evaluar que caracteristicas clinicas, bioquimicas y de imagen vascular pueden ayudarnos a detectar a ninos/as y adolescentes con hipercolesterolemia afectados de HF. Metodos Doscientos veintidos ninos y adolescentes de entre 4 y 18 anos fueron reclutados para participar en un proyecto de deteccion precoz de HF (proyecto DECOPIN). La HF se diagnostico por criterios geneticos o clinicos. Se definio hipercolesterolemia poligenica (HP) cuando el c-LDL >135 mg/dl pero sin criterios clinicos ni geneticos de HF. Participantes con c-LDL Resultados Noventa y un ninos fueron diagnosticados de HF y 23 de HP, y 108 como GC. El grupo HF presento mayores concentraciones de CT, c-LDL, indice ApoB/ApoA1 e indice colesterol ano. El c-HDL fue menor en grupo HF que en el GC. Si bien el c-LDL fue el parametro mas definitorio de HF, el indice ApoB/ApoA1 > 0,82 fue el que de forma aislada mostro mayor sensibilidad y especificad para predecir la presencia de mutacion en el grupo de ninos HF. El grosor de los tendones de Aquiles no mostro diferencias entre grupos. El GIMc fue mayor en los ninos HF sin diferencias significativas. Conclusiones Los niveles de c-LDL son el marcador de HF. Un indice ApoB/ApoA1 > 0,82 puede ser una herramienta util para decidir el estudio genetico en ninos con sospecha de HF.

Resumen Antecedentes y objetivo El sindrome de apnea-hipopnea durante el sueno (SAHS) es un factor de riesgo de arteriosclerosis. Nuestro objetivo fue evaluar la arteriosclerosis subclinica en los pacientes con SAHS y el efecto del tratamiento con continuous positive airway pressure (CPAP, «presion positiva continua de la via aerea superior») sobre el grosor intima-media carotideo (GIMc). Pacientes y metodo Se incluyeron 125 pacientes con sospecha de SAHS. Despues de la polisomnografia, 107 pacientes fueron diagnosticados de SAHS; 58 cumplian criterios de tratamiento con CPAP. El GIMc se midio mediante ecografia a nivel basal y a los 2 anos de seguimiento en 50 pacientes con SAHS en tratamiento con CPAP y 35 SAHS sin criterio de CPAP. Resultados Los valores del GIMc fueron superiores en los pacientes con SAHS respecto a los que no tenian SAHS (665 ± 120 frente a 581 ± 78 μm, p = 0,005), sin asociarse con su nivel de gravedad. La presencia de placas de ateroma fue mas prevalente en los SAHS que en los no SAHS (48 frente a 2%, p = 0,004). En los pacientes con SAHS, la media del GIMc permanecio estable durante el seguimiento en el grupo sin CPAP, y en el grupo tratado con CPAP disminuyo significativamente (679 ± 122 frente a 631 ± 117 μm, p Conclusiones Los pacientes con SAHS presentan un mayor grado de arteriosclerosis subclinica y no se asocia con su gravedad. La ecografia carotidea en el SAHS es un marcador fiable de arteriosclerosis. El tratamiento con CPAP en el SAHS disminuye el GIMc y el riesgo cardiovascular.

Resumen Fundamento y objetivo La obesidad es el principal factor de riesgo del sindrome de apneas-hipopneas del sueno (SAHS). El objetivo es evaluar el efecto de la continuous positive airway pressure (CPAP, «presion positiva continua de la via aerea» a largo plazo en pacientes con SAHS sobre la grasa intraabdominal. Pacientes y metodos Se incluyeron 50 pacientes SAHS con criterio de CPAP y 35 SAHS no candidatos a CPAP con un seguimiento de 2 anos. El visceral adipose tissue (VAT, «tejido adiposo visceral»), el subcutaneous adipose tissue (SAT, «tejido adiposo subcutaneo») y la preaortic intraabdominal fat (PIF, «grasa intraabdominal preaortica») se midieron mediante ecografia. Resultados En el grupo SAHS no candidatos a CPAP, la media del SAT y del VAT no cambio durante el seguimiento, pero se observo un aumento del PIF (55,19 [23,44] frente a 63,45 [23,94] mm, p = 0,021). En los pacientes SAHS tratados con CPAP, la media del VAT y del PIF no se modifico, pero el SAT disminuyo a los 2 anos del tratamiento con CPAP (11,29 [5,69] frente a 10,47 [5,71] mm, p = 0,012). Conclusiones El tratamiento con CPAP a largo plazo en los pacientes SAHS produce una redistribucion de la grasa intraabdominal y se asocia a un perfil antropometrico de menor riesgo cardiovascular.

Background and objective Obesity is the main risk factor for obstructive sleep apnoea (OSA). The aim was to evaluate the long-term effect of continuous positive airway pressure (CPAP) on intraabdominal fat distribution in OSA patients. Patients and methods Fifty OSA patients with and 35 without CPAP treatment criteria were followed-up for 2 years. Visceral and subcutaneous adipose tissue (VAT and SAT) and preaortic intraabdominal fat (PIF) were assessed by sonography. Results In the non-CPAP treated group, SAT and VAT mean values did not change, while a significantly PIF growth was observed (55.19 [23.44] vs. 63.45 [23.94] mm, P = .021). In the CPAP treated group, VAT and PIF mean were not changed, while SAT decreased significantly (11.29 [5.69] vs. 10.47 [5.71] mm, P = .012). Conclusions Long-term CPAP treatment produces intraabdominal fat redistribution and is associated with an anthropometric profile of lower cardiovascular risk in OSA patients.

PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis.There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients.The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C).PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism.

Background and aims Obesity is associated with increased cardiovascular risk. However, the impact of morbid obesity on vascular structure and function is not well understood. This study was designed to appraise subclinical atherosclerosis markers, including carotid intima media thickness (cIMT), endothelial function, and arterial wall stiffness, and their determinants, in morbidly obese patients. Methods and results In this cross-sectional study 194 overweight and obese patients were distributed in morbid-obese patients (MOP, n = 110), obese (OP, n = 84) and overweight patients (OwP, n = 33) groups. Demography, anthropometry, clinical and standard biochemical data were recorded. cIMT, endothelial function, defined as the small artery reactivity index (saRHI), and artery wall rigidity, studied by the augmentation index, were determined. More than 50% of the MOP, OP and OwP had a cIMT above the 75th percentile per age and gender. No differences in cIMT or saRHI were observed, although overweight and obese patients (OOP) had higher arterial rigidity compared with the morbid-obese patients. In a multivariate regression test, while cholesterol was the main determinant of cIMT in overweight and obese patients, glucose metabolism was the determinant in MOP. Conclusion More than half of the population have a cIMT above general population ranges. OwP, OP and MOP have similar cIMT and saRHI. However, OOP have greater arterial wall rigidity. Dysglycemia is the main factor associated with subclinical atherosclerosis in MOP.

Background Low carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or metabolic syndrome (MS), their net effect on vascular function remains unclear. Objective Evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery vascular function, in a cohort of MS patients. Design This cross-sectional study included 160 MS patients. Diet was evaluated by a 3-day food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and saRHI was measured in each patient. Results Individuals in the lowest LCDS quartile (Q1; 45% carbohydrate, 19% protein, 31% fat) had higher saRHI values than those in the top quartile (Q4; 30% carbohydrate, 25% protein, 43% fat) (1.84 ± 0.42 vs. 1.55 ± 0.25, P = .012). These results were similar in T2D patients (Q1 = 1.779 ± 0.311 vs. Q4 = 1.618 ± 0.352, P = .011) and also in all of the MS components, except for low HDLc. Multivariate analysis demonstrated that individuals in the highest LCDS quartile, that is, consuming less carbohydrates, had a significantly negative coefficient of saRHI which was independent of confounders (HR: −0.747; 95%CI: 0.201, 0.882; P = .029). Conclusions These data suggest that a dietary pattern characterized by a low amount of carbohydrate, but reciprocally higher amounts of fat and protein, is associated with poorer vascular reactivity in patients with MS and T2D.

Background and aims Abdominal obesity (AO) is associated with endothelial function (EF) alteration and increased global cardiovascular (CV) risk. Therapeutic lifestyle changes (TLSC) reduce CV risk, but the impact on EF assessed by peripheral artery tonometry (PAT) is unknown. In this study, we aimed to prospectively assess the effects of TLSC on EF measured by PAT in increased CV risk patients with AO. Methods and results 150 patients with AO and moderate CV risk were randomized to groups receiving a one-year intervention of either conventional medical care (control group, CG) or an intensive TLSC program (intervention group, IG). Vascular studies (EF by PAT, intima-media thickness (IMT)) and lifestyle (LS) assessment were performed before and after intervention. The PAT ratio improved in the IG and worsened in the CG. The global CV risk was reduced ( P = 0.017) in the IG due to a significant decrease in systolic blood pressure ( P P = 0.013). More individuals in the IG than in the CG quit smoking ( P = 0.001) and increased their physical activity ( P = 0.014). The improvement in at least two LS components was associated with a PAT ratio increase (2.44 IC: 95% 0.99–6.00, P = 0.051). The PAT ratio increase determined less IMT progression (−1.1 IC: 95% 0.91–1.00, P = 0.053). Conclusions Good adherence to a TLSC program reduces global CV risk and determines PAT ratio improvement. The PAT ratio increase is the main determinant of lower IMT progression.

Resumen Introduccion y objetivos Analizar el impacto de cambios de estilo de vida en la concentracion plasmatica de adipocyte fatty acid-binding protein (FABP4) en pacientes con riesgo cardiovascular. Metodos Se incluyo a 140 pacientes con riesgo cardiovascular sin enfermedad cardiovascular previa en un estudio prospectivo de 1 ano de duracion para evaluar el impacto de cambios terapeuticos de estilo de vida (tabaco, educacion nutricional y actividad fisica) en el riesgo cardiovascular. Resultados Las variaciones de la FABP4 se asociaron inversamente con cambios en la actividad fisica (MET·h/sem). La FABP4 se redujo significativamente en los pacientes que aumentaron su actividad fisica, mientras que aumento en quienes la disminuyeron. Los cambios observados en la FABP4 tambien se asociaron con modificaciones en el indice de masa corporal y la resistencia a la insulina; sin embargo, las correlaciones entre actividad fisica y FABP4 permanecieron significativas tras ajustarlas por variables de confusion. Los cambios en la actividad fisica fueron los principales predictores de las modificaciones en la FABP4. La disminucion de FABP4 se asocio directamente con reducciones de colesterol ligado a las lipoproteinas de baja densidad y apolipoproteina B. Dejar de fumar y la composicion de la dieta no modificaron las concentraciones de FABP4. Conclusiones La concentracion plasmatica de FABP4 puede reducirse aumentando la actividad fisica aerobica. La actividad fisica actua sobre las concentraciones de FABP4 independientemente de la reduccion de peso. Si se pudiera establecer un papel causal de la FABP4 en las alteraciones metabolicas y vasculares, nuestros resultados anadirian un nuevo efecto positivo tanto de la actividad fisica como de la reduccion de la obesidad en el riesgo metabolico y cardiovascular.

The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) microg/l and 19.2 (9.2) microg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia.

4.122; p=0.473). Comment: Our results suggest that in AIS the ASA-non responsive status/platelet insensitivity may be influenced by the previous therapeutic control of the main risk factors to cerebrovascular disease. ASA is an important part of treatment of AIS and its efficacy may be improved in previous high risk cerebrovascular patients, particularly with antihypertensive and antidiabetic therapeutic control.