Autosomal Recessive Hypercholesterolemia Long-Term Cardiovascular Outcomes

BACKGROUND Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. OBJECTIVES Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. METHODS Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. RESULTS We collected data for 52 patients (28 females, 24 males; 31.1 +/- 17.1 years of age…

Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship

Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Regist…

Índice leuco-glucémico en el infarto agudo de miocardio con elevación del ST, un parámetro sencillo y útil en la valoración de las complicaciones

c Leon-Aliz et al.1 publican en este numero un articulo titulado Indice leuco-glucemico como marcador pronostico de la evolucion intrahospitalaria en pacientes con infarto agudo de miocardio con elevacion del ST. Estos autores senalan en su articulo que el indice leucoglucemico elevado tiene, en sujetos ingresados con infarto agudo de miocardio (IAM) con elevacion del ST, una buena correlacion con la mortalidad y las complicaciones (odds ratio [OR] 3,0; IC95%: 1,2-7,3; p 0,005), e indican que este indice, despues de ajustarlo con el analisis multivariado, mantiene de forma independiente un alto valor predictivo de la evolucion y complicaciones de la enfermedad isquemica cardiaca. La importa…

Two-generation cardiovascular disease prevalence in familial hypercholesterolemia

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

Abstract Background The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. Methods Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Sp…

Chronic kidney disease as a cardiovascular risk factor.

: Chronic kidney disease (CKD) is a public health threat with impact in cardiovascular risk. All forms of cardiovascular disease and mortality are more common in CKD. Treatment of cardiovascular risk factors, hypertension, dyslipidemia and diabetes is essential for cardiovascular and kidney protection. CKD is a marker of high or very high cardiovascular risk and its presence require early treatment and specific goals. Lifestyle is a pivotal factor, stopping smoking, reducing weight in the overweight or obese, starting regular physical exercise and healthy dietary pattern are recommended. Office BP should be lowered towards 130/80 mmHg or even lower if tolerated with sodium restriction and s…

Influencia del ejercicio físico moderado sobre el metabolismo lipídico posprandial en pacientes diabéticos tipo 2 no obesos

Fundamento La primera causa de muerte en la diabetes es la cardiopatia isquemica por aterosclerosis coronaria, cuyo desarrollo puede atribuirse, en parte, a alteraciones de las lipoproteinas ricas en trigliceridos (TG). La mayoria de estudios lipidicos en diabeticos se han efectuado en situacion basal (en ayunas); sin embargo, hay indicios de que el aumento posprandial de las lipoproteinas ricas en TG podria ser aterogenico al modificar indirectamente el metabolismo de otras lipoproteinas. El ejercicio fisico influye en el metabolismo lipidico, pero en pacientes con diabetes tipo 2 existen pocos estudios en relacion con sus posibles efectos beneficiosos sobre la lipemia posprandial. El obje…

Classical cardiovascular risk factors according to fasting plasma glucose levels

To compare the prevalence of classical cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in our population according to fasting plasma glucose levels (FPG).We have studied 344 subjects between 20-70 years of age, recruited in a Primary Care Clinic. Subjects were divided into four groups according to their fasting plasma glucose (FPG) values: normal plasma glucose (NG) when FPG5.6 mmol/L; FPG between 5.6 and 6.0 mmol/L (FPG1); FPG between 6.1-6.9 mmol/L (FPG2); and diabetes (DM) FPGor = 7 mmol/L or previous diagnosis of diabetes. Cardiovascular risk factors (hypertension, TC/HDL-C index and Apo B values), presence of the MetS and indirect measure of insulin resistance (HOMA) w…

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test

Abstract Objective Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat. Methods The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50 g fat per m2 body surface) was performed using a commercial liquid preparation of long chai…

Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1/CX3CR1 axis.

Aims Insulin resistance (IR) is a major risk factor for cardiovascular disease and atherosclerosis. Life-threatening acute events are mainly due to rupture of unstable plaques, and the role of vascular smooth muscle cells (VSMCs) in this process in IR, Type 2 diabetes mellitus, and metabolic syndrome (T2DM/MetS) has not been fully addressed. Therefore, the role of VSMC survival in the generation of unstable plaques in T2DM/MetS and the involvement of inflammatory mediators was investigated. Methods and results Defective insulin receptor substrate 2 (IRS2)-mediated signalling produced insulin-resistant VSMCs with reduced survival, migration, and higher apoptosis than control cells. Silencing…

Insulin resistance and familial dyslipidaemias

Síndrome de McCune-Albright: otra forma de neoplasias endocrinas múltiples

Presentamos el caso de una mujer con sindrome de McCune-Albright como paradigma de afeccion tumoral en multiples glandulas endocrinas. El diagnostico de la enfermedad se baso en la presencia de la triada clasica (lesiones hiperpigmentadas cutaneas de color cafe con leche, pubertad precoz y displasia fibrosa). Durante su seguimiento presento hipertiroidismo secundario a bocio multinodular toxico, hiperparatiroidismo, probablemente secundario a hiperplasia paratiroidea, y acromegalia secundaria a adenoma hipofisario productor de hormona de crecimiento. Se comenta la base molecular de la enfermedad y su amplia expresion fenotipica.

Apo E phenotypes and plasma triglycerides in postmenopausal women with hormone replacement therapy

Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects

Abstract There is no doubt about the relationship between LDL-C and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-C has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterised by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-C and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining …

Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?

Abstract Background: Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies. Methods: Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences). Results: We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60…

Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias.

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein chol…

Absence of cardiovascular autonomic dysfunction and vagal pancreatic impairment in idiopathic achalasia of the oesophagus

Abstract  Extra-oesophageal autonomic dysfunction in idiopathic achalasia is not well documented, due to contradictory results reported. We aimed to study the cardiovascular and pancreatic autonomic function in patients with idiopathic achalasia. Thirty patients with idiopathic achalasia (16M/14F; 34.5 ± 10.8 years) and 30 healthy volunteers (13M/17F; 34.8 ± 10.7 years) were prospectively studied. Age >60 years and conditions affecting results of autonomic evaluation were excluded. Both groups underwent the sham feeding test and plasmatic levels of pancreatic polypeptide (PP) were determined by radioimmunoassay (basal, at 5, 10, 20 and 30 min). Cardiovascular parasympathetic (deep breathing…

Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia

Abstract —Plasma lipid response to dietary fat and cholesterol is, in part, genetically controlled. The apolipoprotein A-IV (apoA-IV protein; APOA4, gene) has been shown to influence the response to dietary changes in normolipidemic individuals. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, and no studies are available on the influence of APOA4 mutations on dietary response in these subjects. We studied the effect of 2 common apoA-IV genetic variants (Gln 360 →His and Thr 347 →Ser) on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 67 FH heterozygotes (43 women and 24 men). Subjects were studied at baseli…

Hyperammonemic encephalopathy after urinary diversion. Diet therapy

Influence of Apo A4 genotypes (Apo4-347 mutation) on the lipid response to diet in familial hypercholesterolemia

Effects of a controlled program of moderate physical exercise on insulin sensitivity in nonobese, nondiabetic subjects.

OBJECTIVE: To study the effect of a moderate, aerobic physical exercise program on insulin resistance and its accompanying metabolic changes in a group of healthy, middle-age, nonobese subjects, without modifying oxygen consumption and body weight. DESIGN: The inclusion of subjects was carried out among volunteers from the health personnel of our center, who complied with the inclusion criteria. PARTICIPANTS: Twelve subjects (age 30-60 years, 5 females), nonsmokers, body mass index (BMI) <27 kg/m2 and fasting plasma glucose <6.1 mmol/L. INTERVENTIONS: Insulin resistance was assessed using the Bergmann minimal model modified with insulin, and basal and maximum metabolic rate were measured wi…

Estudio del defecto familiar de unión de la apolipoproteína B100 en una población mediterránea

Fundamento y objetivo Comparar las caracteristicas clinicobioquimicas del defecto familiar de union de la apolipoproteina B100 (DFB) con la hipercolesterolemia familiar (HF) heterocigota en una poblacion mediterranea del sur de Europa donde existen pocos datos al respecto, estudiar la prevalencia y el posible efecto fundador del DFB en una zona de la Comunidad Valenciana y conocer las caracteristicas clinicobioquimicas del DFB. Sujetos y metodo Hemos estudiado a 19 heterocigotos con DFB (8 varones) pertenecientes a 12 familias, portadores de la mutacion R3500Q del gen de la apolipoproteina B, y a 57 heterocigotos con HF (24 varones) geneticamente caracterizados, seleccionados de forma aleat…

Las guías de práctica clínica de manejo de la dislipemia. Una visión transatlántica

Obesidad abdominal, resistencia a la insulina y riesgo metabólico y vascular

Metabolismo lipídico y clasificación de las hiperlipemias

This chapter summarises, and updates, lipid metabolism. Both pathways, exogenous metabolisms route via the chylomicrons, and the endogenous pathway of very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The reverse cholesterol metabolism will also be mentioned. It also includes the current classification of hyperlipidaemias or hyperlipoproteinaemias, with a reminder of the phenotype classification, and further developments of the aetiological classification. Both parts have updated references, with which knowledge of this vast subject can be expanded.

Las recomendaciones de la guía para el diagnóstico y tratamiento del aneurisma de aorta abdominal

Enhanced levels of the light/lymphotoxin-beta receptor inflammatory axis in metabolic syndrome patients

Oxidative stress and antioxidant enzyme values in lymphomonocytes after an oral unsaturated fat load test in familial hypercholesterolemic subjects

Oxidative stress (OS) has been observed in conditions affecting the cardiovascular system. Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. In the postprandial state, circulating lipids and lipoproteins can modulate OS status. Our aim was to study the response of lymphomonocyte OS status and reactive oxygen species by-products after an oral unsaturated fat load test (OFLT) in those with FH and to compare this response with that obtained in normolipidemic, normoglycemic subjects. We studied 12 patients with FH and 20 healthy controls. In both groups, lymphomonocyte, oxidized/reduced glutathione ratio, and malondialdehyde were determ…

Influencia del depósito de grasa abdominal en la respuesta terapéutica a atorvastatina en mujeres con hipercolesterolemia familiar heterocigota

Objetivo Analizar la influencia de parametros antropometricos (tipo y grado de obesidad) sobre el fenotipo lipoproteico y la respuesta terapeutica a atorvastatina en mujeres con Metodos Estudio de intervencion no controlado con 20 mg de atorvastatina al dia (dosis nocturna) en 34 mujeres con hipercolesterolemia familiar heterocigota seleccionadas de forma aleatoria. Resultados El deposito de grasa abdominal influye de forma estadisticamente significativa en los valores de presion arterial y concentraciones plasmaticas basales y postratamiento de los trigliceridos. Existe una interaccion negativa entre el deposito de grasa abdominal y la respuesta terapeutica de cLDL, siendo menores los desc…

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study

Introduction The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with allcause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008-2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to corona…

Inhibition of proprotein convertase subtilisin/kexin type 9 in the treatment of hypercholesterolemia

Peripheral blood levels of CXCL10 are a useful marker for diabetic polyneuropathy in subjects with type 2 diabetes.

BACKGROUND Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus associated with high morbidity and mortality. Major risk factors for DPN include metabolic changes, duration of diabetes, nerve ischaemia and derangements in regeneration and nerve repair programmes. Chemokines have been previously implicated in the pathogenesis of various neuropathies and neuropathic pain processes. The aim of this pilot study was to evaluate the association between the plasma levels of chemokines (CXCL9, CXCL10 and CXCL11) in the presence of DPN in a cohort of type 2 diabetes (T2D) patients. MATERIALS AND METHODS We studied 73 patients with T2D: 36 with DPN and 37 without DPN. D…

Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia

BACKGROUND Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR). MATERIALS AND METHODS A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensiv…

Polymorphisms at theSRBIlocus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) fo…

Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy.

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficien…

Old and new basal insulin formulations: understanding pharmacodynamics is still relevant in clinical practice.

Long-acting insulin analogues have been developed to mimic the physiology of basal insulin secretion more closely than human insulin formulations (Neutral Protamine Hagedorn, NPH). However, the clinical evidence in favour of analogues is still controversial. Although their major benefit as compared with NPH is a reduction in the hypoglycaemia risk, some cost/effectiveness analyses have not been favourable to analogues, largely because of their higher price. Nevertheless, these new formulations have conquered the insulin market. Human insulin represents currently no more than 20% of market share. Despite (in fact because of) the widespread use of insulin analogues it remains critical to anal…

Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.

The aims of this study were to examine the presence of mutations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterolemia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis was carried out following a three-step protocol based on Southern blot and PCR-single strand conformational polymorphism analysis. A randomized clinical trial with simvastatin was conducted in 42 genetically diagnosed subjects with familial hypercholester…

Altered glutathione system is associated with the presence of distal symmetric peripheral polyneuropathy in type 2 diabetic subjects.

Abstract Distal symmetric peripheral polyneuropathy (DSPN) is a highly prevalent complication of diabetes. However, underlying pathophysiological mechanisms are multiple and not well understood. The aim of our study was to analyze the oxidative stress levels in circulating mononuclear cells by measuring the glutathione system, malondialdehyde and oxidized-LDL, in 60 type 2 diabetic patients from a well-characterized cohort of 196 type 2 diabetic patients. Using a nested case–control design, we studied 30 type 2 diabetic patients with distal symmetric polyneuropathy and 30 diabetic controls without this complication, according to the Neuropathy Disability Score. We have found that diabetic p…

Homocisteína plasmática, Lp(a) y marcadores de estrés oxidativo en la vasculopatía periférica del paciente con diabetes tipo 2

Resumen Objetivo Buscar nuevos factores biologicos como el estres oxidativo (EO) y su interaccion con los clasicos, edad, HbA1c, Lp(a) y homocisteina plasmatica asociados con la vasculopatia periferica (VP) del paciente con diabetes tipo 2 (DMT2). Sujetos y metodos Estudiamos 204 diabeticos tipo 2 seleccionados de forma consecutiva de un hospital de referencia y un hospital comarcal de nuestra comunidad autonoma en el periodo comprendido entre enero de 2009 a mayo de 2010. Se trato de un estudio transversal de caso (ITB   1,2. Los parametros clinicobiologicos fueron medidos por procedimientos estandarizados. Resultados Los sujetos fueron divididos en 2 grupos: con VP (ITB > 0,89) o sin VP (…

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia.Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined.Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L) (P&lt;0.05). Postprandial lipemia was similar…

Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influe…

Pancitopenia en un varón de 59 años con feocromocitoma maligno tratado con I-131 metaiodobencilguanidina

Presentamos un paciente diagnosticado de feocromocitoma maligno silente que en su evolucion presento metastasis en cuerpos vertebrales, huesos iliacos, ambos pulmones e higado. El paciente solo referia lumbalgia intermitente y las determinaciones urinarias de catecolaminas y sus metabolitos fueron normales. Se realizo inicialmente suprarrenalectomia derecha y se aplico telecobaltoterapia externa en la region L4-S2 (dosis total de 20 Gy), para control del dolor y por inicio de compresion radicular. Posteriormente, de forma paliativa se administro una dosis unica de 200 mCi de 131-I metaiodobencilguanidina (MIBG), desarrollando al mes una pancitopenia con neutropenia grave, que preciso antibi…

La auténtica dimensión del colesterol-no-HDL: colesterol aterogénico

Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real meas…

Semiquantitative multiplex PCR: a useful tool for large rearrangement screening and characterization

Methods presently employed for detection of large rearrangements have several drawbacks, such as the amount of sample and time required, technical difficulty, or the probability of false-negative carriers. Using the low-density-lipoprotein receptor (LDLR) gene, whose mutations are responsible for familial hypercholesterolemia (FH), we have developed a procedure to detect large rearrangements in this gene based on semiquantitative PCR, with important improvements as compared to previous methods. Our method covers the complete LDLR gene and introduces an internal control in the reaction. The procedure discriminates the four different large rearrangements (two deletions and two insertions) tha…

Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population

Few data are available on genotype-phenotype interactions among familial hypercholesterolemia (FH) patients in South European populations and there are no data about the influence of R3500Q mutation on lipoprotein phenotype compared to low-density lipoprotein receptor (LDLR) mutations. The objective of the study is to analyze the influence of mutations in the LDLR and apolipoprotein B (apoB) genes on lipoprotein phenotype among subjects clinically diagnosed of FH living in East Spain. In all, 113 FH index patients and 100 affected relatives were studied. Genetic diagnosis was carried out following a protocol based on Southern blot and PCR-SSCP analysis. A total of 118 FH subjects could be c…

Cuantificación de insulinorresistencia con los valores de insulina basal e índice HOMA en una población no diabética

Fundamento Calcular la prevalencia y definir el sindrome de insulinorresistencia mediante la determinacion de insulinemia basal y el indice HOMA, y estudiar su relacion con otros componentes del sindrome metabolico. Sujetos y metodo Estudiamos una poblacion de 292 sujetos no diabeticos, de ambos sexos y edades entre 20 y 65 anos, seleccionados por un metodo de muestreo simple aleatorio entre los que consultaron durante un ano en un centro de salud (en el area metropolitana de Valencia), mediante un metodo de busqueda oportunista. De ellos se selecciono a un subgrupo formado por 96 sujetos que no tenian caracteristicas clinicas ni analiticas del sindrome de insulinorresistencia, y se estudia…

Consenso Delphi sobre el manejo de la dislipidemia en pacientes con alteración del metabolismo de la glucosa: estudio Diana

Objectives The aim of the present study was to develop a multidisciplinary consensus based on the Delphi system to establish clinical recommendations for the management of dyslipidaemia when hyperglycaemia is present, and the relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. Methods The questionnaire developed by the scientific committee included four blocks of questions about dyslipidaemia in patients with impaired glucose metabolism. The results of the first two blocks are presented here: a) management of dyslipidaemia; b) relevant factors that should be taken into consideration when prescribing and monitoring treatment with s…

Management of Dyslipidemia in the Metabolic Syndrome

In order to characterize the metabolic syndrome it becomes necessary to establish a number of diagnostic criteria. Because of its impact on cardiovascular morbidity/mortality, considerable attention has been focussed on the dyslipidemia accompanying the metabolic syndrome. The aim of this review is to highlight the fundamental aspects of the pathophysiology, diagnosis, and the treatment of the metabolic syndrome dyslipidemia with recommendations to clinicians. The clinical expression of the metabolic syndrome dyslipidemia is characterized by hypertriglyceridemia and low levels of high-density lipoprotein-cholesterol (HDL-C). In addition, metabolic syndrome dyslipidemia is associated with hi…

Avances en el tratamiento de la hipercolesterolemia

Advances in cholesterol-lowering interventions Abstract Numerous epidemiological and prospective studies have shown a direct relationship between total cholesterol and low-density lipoprotein cholesterol (LDL-C) and cardio- vascular disease (cardiovascular morbidity and mortality). In many intervention studies with more than 100,000 subjects, statins have shown a powerful and significant reduction of cardiovascular events and a decrease in cardiovascular and overall mortality, far superior to those produced by any other lipid-lowering group.

Prevalence of plasma lipid abnormalities and its association with glucose metabolism in Spain: The di@bet.es study

Abstract Introduction Dyslipidemia is a significant contributor to the elevated CVD risk observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia and its association with glucose metabolism status in a representative sample of the adult population in Spain and the percentage of subjects at guideline-recommended LDL-C goals. Material and methods The di@bet.es study is a national, cross-sectional population-based survey of 5728 adults. Results A total of 4776 subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only 13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities were found in 56.8% of Spanish adults: 23.3% with high LDL…

Postprandial triglyceridaemia is modulated by insulin resistance but not by grade of obesity in abdominal and morbid obese subjects

Background Obesity is associated with high cardiovascular risk. Postprandial lipidaemia has been associated with cardiovascular disease risk. Our aim was to identify whether anthropometric parameters, insulin resistance (IR) and/or fasting plasma triglycerides may determine postprandial changes in lipoprotein concentrations in abdominal and morbid obese subjects. Methods We have studied 20 non-diabetic, normolipidaemic subjects with abdominal obesity, 20 morbid obese subjects and 20 healthy individuals, that have similar age and gender. In all of them a standardised oral fat load test (OFLT) with unsaturated fat was performed. Results During the OFLT, the postprandial triglycerides response…

Effects of marathon running on plasma total homocysteine concentrations.

Summary Aims There is evidence of an excess of acute cardiovascular (CV) events in marathon runners. High plasma total homocysteine (tHcy) concentrations are a recognised risk factor for CV events. Therefore, we investigated the changes in plasma tHcy concentrations 24 h before and after a marathon race. Methods and results Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23–49 years, were studied the day before and 24 h after finishing a marathon race. None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion of supplements of vitamins (B12, B6, folic acid) was allowed. Results Changes in plasma folate and plasma vitamin B12 concentrations were no…

Tratamiento integral de la dislipidemia diabética: beneficios y nuevas alternativas terapéuticas

Diabetic dyslipidemia, characterized by the lipid triad (elevated plasma triglycerides, low HDL cholesterol and predominance of small, dense LDL particles), is a significant contributor to the elevated cardiovascular risk of type 2 diabetic patients. Statin monotherapy has shown, in different prospective trials, significant reductions in cardiovascular events and mortality. However, the residual risk in these subjects remains elevated, probably due to the incomplete control of diabetic dyslipidemia. In this review we discuss the global therapeutic approach, underlying the need of combining statins with agents that more effective in reducing triglycerides and elevating HDL cholesterol, even …

Efecto del género y de la obesidad en la lipemia posprandial en sujetos sanos normolipidémicos no diabéticos y sujetos con hiperlipemia familiar combinada

Introduccion Un nuevo metodo basado en la autodeterminacion de trigliceridos (TG) capilares permite un mejor conocimiento de la lipemia posprandial (LP). Los objetivos de nuestro estudio son analizar el efecto del genero y la obesidad sobre la LP valorada por medicion capilar de TG diurnos mediante Accutrend GCT® en sujetos sanos y sujetos con hiperlipemia familiar combinada (HFC). Material y metodos Hemos estudiado a 23 sujetos con HFC no relacionados entre si (10 hombres) y a 45 sujetos (29 hombres) normolipidemicos no diabeticos. Todos ellos realizaron tres perfiles diarios de TG capilares durante una semana. Resultados En los sujetos sanos normolipidemicos no diabeticos encontramos valo…

Oxidative Stress and Chronic Inflammatory State Present in Familial Hypercholesterolemia is Reduced After a Fat Overload Rich in Unsaturated Fatty Acids

Determinantes de la lipemia posprandial medida como perfil diurno de triglicéridos en personas no diabéticas con normolipemia

Fundamento y objetivo: Conocer los determinantes clinicos y biologicos de la lipemia posprandial, medida con la autodeterminacion diurna de trigliceridos en sangre capilar (TGc), en personas sin dislipemia ni diabetes. Pacientes y metodo: Hemos estudiado a 76 personas sanas (45 mujeres premenopausicas) con normolipemia y sin diabetes. La determinacion de los TGc se realizo mediante Accutrend® durante 3 dias en 6 puntos establecidos: ayunas, inmediatamente antes y 3 h despues de comer y de cenar, y antes de acostarse. Se midio el area bajo la curva de TGc (ABC-TGc) como expresion de la lipemia posprandial diurna. Resultados: El ABC-TGc fue significativamente mayor en los varones (26,20 [11,0…

Importancia de la dislipidemia en la enfermedad cardiovascular: un punto de vista

The authors present their view on the prevention of cardiovascular diseases, accepting the European ESC/EAS guidelines. They consider that the aim of the lipid control, based on LDL-C goals, is essential for the prevention and treatment of cardiovascular diseases. In subjects with metabolic syndrome (mainly, abdominal obesity, pre-diabetes and diabetes), the primary objective should be apoB or Non-HDL-C, which are better associated with cardiovascular risk. The treatment must be lifestyle changes and control of other risk factors. After calculating cardiovascular risk, statins are the first therapeutic step, with the strength and dose needed to achieve LDL-C goals. If targets are not achiev…

Estudio de los valores plasmáticos de Lp(a) en el defecto familiar de unión de la apo B 100 en una población mediterránea del sur de Europa

Aims: 1) to study lipoprotein (a) (Lp(a)) plasma values in subjects with familial ligand-defective apo B 100 (FDB). Methods: We studied 19 heterozygous FDB subjects (8 males) from 12 families, carriers of R3500Q mutation on apo B gene and 90 controls (34 males). The genetic diagnosis was established with PCR-SSCP analysis and automatic sequencing. In all subjects plasma lipids, apoli-poprotein B and Lp(a) levels were determined with standard procedures. Results: Subjects carriers of R3500Q mutation on apo B gene have significantly higher plasma Lp(a) and log transformed Lp(a) values and prevalence of Lp(a) > 30 cut point for coronary heart disease than controls. Conclusions: Subjects with F…

Increased plasma xanthine oxidase activity is related to nuclear factor kappa beta activation and inflammatory markers in familial combined hyperlipidemia

Abstract Background and aims Xanthine oxidase (XO) has been described as one of the major enzymes producing free radicals in blood. Oxidative stress and inflammatory processes have been implicated in the pathogenesis of endothelial dysfunction and the progression of atherosclerosis but until now, there is little data about the influence of vascular prooxidant systems and inflammation in familial combined hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in FCH and if it was related to the inflammatory process represented by NFkB, IL-6 and hsCRP, and assessing the correlation between XO activity and insulin resistance (IR). Method and results 40 Non-related subje…

Misclassification of subjects with insulin resistance and associated cardiovascular risk factors by homeostasis model assessment index. Utility of a postprandial method based on oral glucose tolerance test

Different methods are available for assessing insulin sensitivity in the fasting state. However, insulin resistance (IR) is initially a postprandial disturbance; and usually, when basal (fasting) disturbance appears, the process has been in progress for some time. Our aim was to investigate if a postprandial measurement, performing an oral glucose tolerance test (OGTT), is more sensitive than fasting values. We wished to identify early IR states in healthy, nonobese individuals and ascertain if this situation was associated with other cardiovascular risk factors. A total of 90 nonobese, nondiabetic, and nonsmoker individuals were studied. They were divided into 3 groups according to IR stat…

Association of C677T polymorphism in MTHFR gene, high homocysteine and low HDL cholesterol plasma values in heterozygous familial hypercholesterolemia.

Aim: to investigate the association of C677T polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene, homocysteine plasma values (Hcy), and plasma HDL cholesterol in heterozy-gous familial hypercholesterolemia (hFH).Methods: One hundred and twenty-five hFH subjects were studied. Plasma lipid, lipoprotein, vitamin B12, folic acid and Hcy values were determined. C677T polymorphism in the MTHFR gene was detected by SSCP-PCR. Genetic diagnosis of FH was determined by a three-step protocol using SSCP-PCR, Southern blot, long PCR and automatic sequencing.Results: We found significant differences in plasma HDL-C (CC 1.39±0.34, CT 1.33±0.39 and TT 1.14±0.26 mmol/L, p=0.028) between th…

Estudio de los valores de 8-oxo-7,8-dihidro-2’-desoxiguanosina como marcador de estrés oxidativo del ADN en pacientes con hiperlipemia familiar combinada

Fundamento y objetivo: Comparar los valores de 8-oxo-7,8-dihidro-2'-desoxiguanosina (8-oxo-dG) como marcador de estres oxidativo entre personas sanas y pacientes con hiperlipemia familiar combinada (HFC), modelo de dislipemia mixta con resistencia a la insulina y cardiopatia isquemica precoz, y estudiar su relacion con parametros clinicobiologicos de resistencia a la insulina. Sujetos y metodo: Se ha analizado a 40 pacientes (15 mujeres) no relacionados entre si y diagnosticados de HFC y a 20 sujetos sanos (8 mujeres) normolipemicos y no diabeticos. Se recogieron de forma estandarizada parametros clinicos, antropometricos y bioquimicos: perfil lipidico, glucemia e insulinemia basales y dete…

Familial Combined Hyperlipidemia, Metabolic Syndrome and Cardiovascular Disease

Our aim was to investigate the relationship between metabolic syndrome and cardiovascular disease (i.e., survivors of myocardial infarction) in patients with familial combined hyperlipidemia (FCH). We compared a group of 20 male patients with FCH who had survived a myocardial infarction with two other groups matched for age and body mass index, comprising 20 individuals with FCH who had not had a myocardial infraction and 20 control subjects. Plasma lipid, glucose, and insulin levels were determined. Metabolic syndrome was judged to present on the basis of World Health Organization (WHO) and National Cholesterol Education Program-Adult treatment panel (NCEP-ATPIII) criteria. Differences bet…

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test

Factores asociados con el ingreso hospitalario de pacientes diabéticos con ulceración en el pie

Fundamento Identificar y analizar los factores asociados con el ingreso hospitalario en diabeticos con ulceras en los pies, con el fin de identificar y tratar los pacientes de alto riesgo y evitar su ingreso hospitalario, que es la mayor fuente de gasto sanitario debido al pie diabetico. Sujetos y Metodo Hemos estudiado a 108 diabeticos (59 varones, edad media [DE] 68 [11] anos, 100 con diabetes tipo 2, con 16,4 [10,3] anos de evolucion) que acudieron a la unidad del pie diabetico desde enero 1996 hasta septiembre de 1997 con ulceras en los pies. En la primera visita se recogieron parametros clinicos y bioquimicos de riesgo en un protocolo clinico. Los sujetos fueron seguidos una media de 2…

FABP4 plasma levels are increased in familial combined hyperlipidemia

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 hom…

Hipoglucemia grave y prolongada secundaria a cotrimoxazol en sujeto con factores predisponentes

Association between the TaqIB polymorphism in the cholesteryl ester transfer protein gene locus and plasma lipoprotein levels in familial hypercholesterolemia

Abstract Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides (TG) and cholesteryl ester between lipoprotein particles. Subjects with familial hypercholesterolemia (FH) have been reported to have higher CETP activities, which could contribute to the lower high-density lipoprotein-cholesterol (HDL-C) levels and increased cardiovascular risk observed in some of these patients. Several polymorphisms have been reported in the CETP locus; the common TaqlB polymorphism is associated, in normolipidemic subjects, with decreased CETP activity and levels and with increased HDL-C levels. No data is available on the influence of this polymorphism in FH subjects. We have e…

Sobrecarga oral de glucosa y riesgo cardiovascular

Registro de hipertrigliceridemias de la Sociedad Española de Arteriosclerosis

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influe…

Los niveles plasmáticos de IL-18 se relacionan con la insulinemia y están modulados por polimorfismos del gen de IL-18

INTRODUCTION Atherosclerosis is an inflammatory chronic disease influenced by multiple factors. Different prospective studies have shown that plasmatic levels of inflammatory markers were related to atherosclerosis and cardiovascular disease. OBJECTIVE To evaluate whether plasmatic levels of interleukin 18 (IL-18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and its possible association with insulin levels and other cardiovascular risk factors. METHODS 746 individuals were studied for a period of two years by opportunistic selection in the metropolitan area of Valencia. Parameters of lipid and glucose metabolism were analyzed by standard methodology. IL-18 was m…

Identificación y caracterización del primer español con defecto homocigoto familiar de unión de la apolipoproteína B

Fundamento El defecto familiar de union de la apolipoproteina B-100 (DFB) es una enfermedad hereditaria autosomica dominante debida a mutaciones localizadas en el gen de la apolipoproteina B-100, clinicamente indistinguible de la hipercolesterolemia familiar. Describimos el primer homocigoto espanol para el DFB. Metodos Estudiamos por tecnica de PCR–SSCP la mutacion R3500Q en los familiares de primer y segundo grado de la familia con DFB previamente descrita por nuestro grupo. Ademas, analizamos la actividad del receptor de LDL en un ensayo con LDL conjugada con oro coloidal. Resultados El paciente presenta en ambos alelos la mutacion R3500Q causante de DFB. El estudio de la actividad del r…

Value of the Definition of Severe Familial Hypercholesterolemia for Stratification of Heterozygous Patients

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS crite…

Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento ( I ). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the associa…

Chronic kidney disease and dyslipidaemia

Chronic kidney disease (CKD) has to be considered as a high, or even very high risk cardiovascular risk condition, since it leads to an increase in cardiovascular mortality that continues to increase as the disease progresses. An early diagnosis of CKD is required, together with an adequate identification of the risk factors, in order to slow down its progression to more severe states, prevent complications, and to delay, whenever possible, the need for renal replacement therapy. Dyslipidaemia is a factor of the progression of CKD that increases the risk in developing atherosclerosis and its complications. Its proper control contributes to reducing the elevated cardiovascular morbidity and …

COSMIC project : consensus on the objectives of the metabolic syndrome in clinic

Juan Pedro-Botet,1 Juan F Ascaso,2,3 Vivencio Barrios,4,5 Alejandro De la Sierra,6 Javier Escalada,7,8 Jes&uacute;s Mill&aacute;n,9 Jose M Mostaza,10 Pablo P&eacute;rez-Mart&iacute;nez,8,11 Xavier Pint&oacute;,8,12 Jordi Salas-Salvad&oacute;,8,13 Pedro Valdivielso14 1Lipids and Vascular Risk Unit, Hospital del Mar, Universitat Aut&ograve;noma de Barcelona, Barcelona, Spain; 2Endocrinology and Nutrition Service, Hospital Cl&iacute;nico, Universitat de Valencia, Valencia, Spain; 3INCLIVA Research Institute, Diabetes and Metabolic Diseases Ciber (Networked Biomedical Research Centres &ndash; CIBERDEM), Carlos III, Valencia, Spain; 4Cardiology Service, Hospital Universitario Ram&oacute;n y Caja…

Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus.

Background To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients. Methods Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, HbA1c and microalbuminuria were measured using standard procedures. Results Plasma Hcy, microalbuminuria, HbA…

Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia

We have examined the apo AI - 75 (G/A) and apo AI + 83(MspI +/-) polymorphisms at the APOA1 gene locus for associations with plasma lipid levels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozygotes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35%, fat, 10% saturated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet. No gender-related differences for any of the lipid variables examined were found and the data were analyzed for men and women combined. For the apo AI - 75 (G/A) polymorphism, there were 51 G/G and 18 G/A subjects. At baseline, G/A subjects showed significantly lower total ch…

Waist to hip ratio as a marker of insulin resistance in healthy subjects

Insuficiencia mitral de etiología desconocida en paciente de 20 años

Papel de la dislipemia aterogénica en el desarrollo del síndrome metabólico

Fundamento y objetivo Averiguar si el diagnostico de sindrome metabolico (SM) definido por los criterios de la International Diabetes Federation (IDF) en 2005 identifica a un mayor numero de sujetos con dislipemia aterogenica de elevado riesgo cardiovascular que los criterios del National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP-III). Pacientes y metodo Estudiamos a una poblacion de 344 sujetos no diabeticos (158 varones y 186 mujeres), de edades comprendidas entre 20 y 70 anos, seleccionados por un metodo de muestreo simple aleatorio entre los que consultaron durante un ano en un centro de salud en el area metropolitana de Valencia (metodo de busqueda oportunista).…

Autosomal Recessive Hypercholesterolemia

Abstract Background Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. Objectives Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. Methods Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. Results We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years…

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 1…

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia.

Eur J Clin Invest 2010; 40 (2): 89–94 Abstract Background  Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. Materials and methods  Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear c…

Riesgo cardiovascular residual de origen lipídico. Componentes y aspectos fisiopatológicos

Resumen Es indudable la relacion del cLDL y el riesgo cardiovascular, asi como de los beneficios del tratamiento con estatinas. Una vez conseguido el objetivo de cLDL, son notables las evidencias que demuestran la persistencia de un elevado riesgo cardiovascular, concepto denominado riesgo residual. El riesgo residual de origen lipidico se fundamenta en la dislipidemia aterogenica, caracterizada por un aumento de trigliceridos y de las lipoproteinas ricas en trigliceridos, un descenso del cHDL y alteraciones cualitativas de las particulas LDL. Las medidas mas utilizadas para identificar esta dislipidemia se basan en la determinacion de colesterol total, trigliceridos, HDL, colesterol no HDL…

Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease that increases with age. Because of this, and due to its chronic complications, T2DM causes high human, social, and financial costs. In addition, the elderly population with T2DM has a marked clinical heterogeneity. Therefore, our main objective was to analyze the relationship of age with the clinical and biological manifestations of the disease and the prevalence of chronic complications in patients with T2DM.A cross-sectional study of a large population with T2DM (n=405) randomly selected from a Diabetes Unit and 2 health care centers (60%). The clinical, anthropometric, and biochemical variables of the subjects were c…

Control del perfil lipídico global

Resumen Se revisa la importancia del control lipidico global en la prevencion cardiovascular. Diversos estudios y metaanalisis demuestran que el control del colesterol LDL mantiene aun un elevado riesgo cardiovascular, que se relaciona con la presencia de lipoproteinas ricas en trigliceridos, y por ello con aumento de los trigliceridos plasmaticos y de los valores de apolipoproteina B que contienen estas lipoproteinas. La importancia de esta relacion se debe al cambio ocurrido en los ultimos anos en el perfil lipidico de nuestra poblacion, relacionado con el aumento de obesidad y de resistencia a la insulina; este perfil se denomina dislipidemia aterogenica. Asi, la hipertrigliceridemia deb…

Oxidative stress and mrna expression after an oral unsaturated fat load test in subjects with abdominal obesity

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population

SUMMARY Background: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points fo…

Evaluation of clinical diagnosis criteria of familial ligand defective apoB 100 and lipoprotein phenotype comparison between LDL receptor gene mutations affecting ligand-binding domain and the R3500Q mutation of the apoB gene in patients from a South European population

Familial hypercholesterolemia (FH) and familial defective apoB 100 (FDB) are characterized by increased plasma low-density lipoprotein cholesterol (LDLc) levels and risk of coronary heart disease (CHD). FDB is clinically indistinguishable from FH. The aims of this study were to evaluate clinical diagnosis criteria for FDB and to compare the lipoprotein phenotype between carriers of LDL receptor (LDLR) gene mutations that affect the ligand-binding domain and subjects with the R3500Q mutation in apoB gene. We studied 213 subjects (113 probands) with FH and 19 heterozygous FDB subjects. Genetic diagnosis was determined by following a protocol based on Southern blot and polymerase chain reactio…

Management of homozygous familial hypercholesterolaemia in two brothers

Homozygous familial hypercholesterolaemia (HoFH) is a rare, genetic disorder of abnormally high levels of low-density lipoprotein cholesterol (LDL-C) requiring aggressive interventions to retard the evolution of atherosclerotic cardiovascular disease. We treated two brothers (ages 46 years and 47 years) with HoFH with statins, lipoproteinapheresis (LA) and the microsomal triglyceride transfer protein inhibitor lomitapide. Both brothers carried the p.Thr434Arg homozygous LDLR mutation and had childhood total cholesterol levels >700 mg/dL. Inter-LA LDL-C levels remained high; therefore, they were given escalating doses of oral lomitapide (5–10 mg/day). One brother was able to maintain LDL-C l…

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting.Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state.Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio &amp;gt;20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after admi…

Polymorphisms in endothelin system genes, arsenic levels and obesity risk.

Background/objectivesObesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity.Subjects/methodsWe analyz…

Documento de consenso sobre el manejo de la dislipemia aterogénica de la Sociedad Española de Arteriosclerosis

Resumen Documento de posicionamiento y resumen de las recomendaciones recientemente publicadas por el Grupo de Trabajo de Dislipemia Aterogenica de la Sociedad Espanola de Arteriosclerosis y por la Sociedad Europea de Arteriosclerosis.

Cardiovascular autonomic neuropathy in type 1 diabetic patients with and without peripheral neuropathy.

One hundred Type 1 diabetic patients (54 men, 46 women) mean age 28.9 +/- 8.4 years, were selected from among individuals referred to our hospital, with no previous diagnosis of diabetic chronic complications including diabetic neuropathy. After clinical and physical examinations, subjects were divided into two groups: with (n = 37) and without (n = 63) peripheral neuropathy. The percentage of subjects with cardiovascular autonomic neuropathy (AN), diagnosed by positive results to at least two of the five cardiovascular tests (Valsalva ratio, EI ratio, 30/15 ratio, blood-pressure response to standing up and handgrip test), was 40%: 72.9% in the group with peripheral neuropathy and 20.6% in …

Documento de consenso de la Sociedad Española de Arteriosclerosis (SEA) para la prevención y tratamiento de la enfermedad cardiovascular en la diabetes mellitus tipo 2

Este artículo se encuentra disponible en la siguiente URL: https://www.elsevier.es/es-revista-clinica-e-investigacion-arteriosclerosis-15-articulo-documento-consenso-sociedad-espanola-arteriosclerosis-S0214916818300846 This is the pre-peer reviewed version of the following article: Ruiz-García, A., Arranz-Martínez, E., Morón-Merchante, I., Pascual-Fuster, V., Tamarit, JJ., Trias-Villagut, F. et al. (2018). Documento de consenso de la Sociedad Española de Arteriosclerosis (SEA) para la prevención y tratamiento de la enfermedad cardiovascular en la diabetes mellitus tipo 2. Clínica e Investigación en Arteriosclerosis, vol. 30, supl. 1 (julio), pp. 1-19, which has been published in final form …

Consensus document on the management of the atherogenic dyslipidaemia of the Spanish Society of Arteriosclerosis.

Positioning document and summary of recommendations recently published by the Working Group on Atherogenic Dyslipemia of the Spanish Society of Arteriosclerosis and by the European Society of Arteriosclerosis.

Enhanced reduction in oxidative stress and altered glutathione and thioredoxin system response to unsaturated fatty acid load in familial hypercholesterolemia.

Abstract Objectives Familial hypercholesterolemia (FH) is characterized by increased oxidative stress (OS) levels. In the postprandial state, lipids and lipoproteins modulate OS status through their impact on pro-oxidant and antioxidant mechanisms. The objective of this study was to evaluate in patients with FH the response to an unsaturated oral fat load test (OFLT) by analyzing the mRNA levels of genes involved in the glutathione and thioredoxin antioxidant systems. Design and Methods We analyzed 14 FH patients and 20 normolipidemic and normoglycemic controls. In both groups, mRNA values of antioxidant enzyme genes (glutathione and thioredoxin systems) were determined at baseline and at 2…

Utilidad de la ultrasonografía endoscópica para el diagnóstico de localización de tumores neuroendocrinos pancreáticos: presentación de 2 insulinomas benignos

Los insulinomas son tumores neuroendocrinos que se manifiestan por episodios de hipoglucemia de ayuno. El diagnostico se basa en la sospecha clinica, que debe ir seguida de la demostracion de hiperinsulinismo y la localizacion tumoral. Sin embargo, la localizacion no siempre es posible con las tecnicas de imagen habituales, por lo que se debe recurrir a otras mas complejas. Presentamos 2 casos de insulinomas cuya localizacion tumoral no fue posible con tecnicas de imagen convencionales, pero si con ultrasonografia endoscopica.

Indications of PCSK9 inhibitors in clinical practice. Recommendations of the Spanish Society of Arteriosclerosis (SEA), 2019

A group of experts convened by the Spanish Society of Arteriosclerosis (SEA) has been in charge of updating the SEA document on the indications of PCSK9 inhibitors (PCSK9i) in clinical practice that was published in 2016. This update is justified by the fact that the data from clinical trials carried out on a large scale with PCSK9i have shown that in addition to their high potency to lower atherogenic cholesterol, they reduce the risk of atherosclerotic cardiovascular disease, both in patients with stable disease, and with recent disease, and with a high degree of security. This update provides the recommendations and level of evidence for the prescription of iPCSK9 in patients with homozy…

Asociación de factores lipídicos, genotipo de APOE y tipos de mutación del gen del receptor de LDL con el infarto agudo de miocardio en sujetos con hipercolesterolemia familiar heterocigota

Fundamento Evaluar la relacion de los lipidos, del genotipo de APOE y del tipo de mutacion delgen del receptor de LDL, clasificandolas en nulas y no nulas, sobre la prevalencia de infartoagudo de miocardio (IAM) en individuos heterocigotos con hipercolesterolemia familiar (HF) delsur de Europa, donde existen pocos datos al respecto. Pacientes y metodo Se trata de un estudio transversal que compara individuos con HF e IAM(n = 32) y a individuos con HF sin IAM (n = 76) mayores de 35 anos (41 varones y 67 mujeres).En 88 sujetos se establecio el diagnostico genetico, siendo divididos en portadores de mutacionesnulas o no nulas del gen del receptor de LDL. Se han comparado los factores clasicosd…

Estándares SEA 2019 para el control global del riesgo cardiovascular

One of the main goals of the Spanish Society of Arteriosclerosis is to contribute to a wider and greater knowledge of vascular disease, its prevention and treatment. Cardiovascular diseases are the leading cause of death in our country and also lead to a high degree of disability and health expenditure. Arteriosclerosis is a multifactorial disease, this is why its prevention requires a global approach that takes into account the different risk factors with which it is associated. Thus, this document summarizes the current level of knowledge and integrates recommendations and procedures to be followed for patients with established cardiovascular disease or high vascular risk. Specifically, t…

Polymorphisms of the UCP2 gene are associated with body fat distribution and risk of abdominal obesity in Spanish population

Eur J Clin Invest 2011 Abstract Background  Increased accumulation of fat results from an imbalance between energy expenditure and intake, being modulated by different environmental and genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins able to spend energy generating heat. Therefore, variations in these genes are good candidates as potential modulators of body fat accumulation. Our aim was to investigate the possible association of genetic variations of the gene codifying the UCP2 protein with obesity and fat distribution. Design  We performed a cross-sectional study in 2367 individuals from two population-based studies from different regions of Spain. The Horte…

Systemic inflammation in primary hypercholesterolemia results in platelet and leukocyte activation and their enhanced endothelial adhesiveness

Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant disease characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C). Phenotypic expression is highly variable, being influenced by diet, age, gender, body mass index, apolipoprotein E genotype and type of LDL-receptor gene mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate lipid levels in several populations. To analyse the effect of this polymorphism in the lipid phenotype expression of FH and treatment response, we studied a sample of 222 Spanish FH patients, of whom 147 were studied before and after trea…

Altered Semmes–Weinstein monofilament test results are associated with oxidative stress markers in type 2 diabetic subjects

Abstract Background Different lines of evidence suggest that oxidative stress (OS) is implicated in the pathogenesis of diabetic neuropathy. The Semmes–Weinstein monofilament (SWM) test is an efficient tool for evaluating diabetic polyneuropathy and diabetic foot. In this study, we analyzed the association between OS markers and altered SWM test results in type 2 diabetes (T2DM) patients. Methods Seventy T2DM patients were studied and 34 showed altered SWM results. The clinical and biochemical parameters were determined using standardized methods. Levels of oxidized glutathione (GSSG) and malondialdehyde (MDA) were measured in circulating mononuclear cells using high-performance liquid chro…

Diferencias en las características clínico-biológicas y prevalencia de complicaciones crónicas en relación con el envejecimiento de pacientes con diabetes tipo 2

Resumen La diabetes tipo 2 (DMT2) es una enfermedad con elevada prevalencia que aumenta con la edad. Por este motivo y por sus complicaciones cronicas genera elevado coste humano, social y economico en la poblacion mayor. Ademas, la poblacion mayor con DMT2 presenta una marcada heterogeneidad clinica. Por lo que nuestro objetivo principal es conocer como se relaciona la edad con el fenotipo clinico-biologico y cual es la prevalencia de complicaciones cronicas en el paciente con DMT2. Material y metodos Estudio transversal de una amplia poblacion de DMT2 (n = 405) seleccionada de forma aleatoria de una Unidad de Diabetes y 2 centros de salud (60%). En estos sujetos se recogieron variables cl…

Hipercolesterolemia familiar homocigota: adaptación a España del documento de posición del grupo de consenso sobre hipercolesterolemia familiar de la Sociedad Europea de Arteriosclerosis. Documento de Consenso de la Sociedad Española de Arteriosclerosis (SEA) y la Fundación Hipercolesterolemia Familiar (FHF).

Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening disease characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). The Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) has recently published a clinical guide to diagnose and manage HoFH (Eur Heart J. 2014;35:2146-57). Both the Spanish Society of Atherosclerosis (SEA) and Familial Hypercholesterolaemia Foundation (FHF) consider this European Consensus document of great value and utility. However, there are particularities in our country which advise to ha…

Mitral regurgitation of unknown etiology in a 20-year-old patient

Los fibratos en la prevención primaria de la enfermedad cardiovascular. Comentarios a los resultados de una revisión sistemática de la Colaboración Cochrane

Resumen Los fibratos son un grupo de hipolipidemiantes que reducen los trigliceridos, elevan las lipoproteinas de alta densidad y disminuyen la fraccion de particulas de LDL pequenas y densas. Recientemente, se han publicado los resultados de un estudio de la Colaboracion Cochrane sobre su eficacia y seguridad en la prevencion primaria de la enfermedad cardiovascular. Este estudio incluye una revision sistematica y un metaanalisis de 6 estudios (16.135 pacientes) que evaluan, en personas en prevencion primaria, los beneficios clinicos de los fibratos comparados con el uso de un placebo o de otros hipolipidemiantes. Concluyen que, comparados con placebo, los fibratos son utiles para reducir …

Colesterol-no HDL como objetivo terapéutico

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological st…

Postprandial Changes in Chemokines Related to Early Atherosclerotic Processes in Familial Hypercholesterolemic Subjects: A Preliminary Study.

Familial hypercholesterolemia (FH) is associated with higher levels of inflammatory mediators such as chemokines, which contribute to an increased risk of premature atherosclerosis in these patients. We studied the response of chemokines related to early atherosclerotic processes during an oral unsaturated fat load test (OFLT) in patients with heterozygous FH and compared this response to normolipidemic and normoglycemic subjects.Blood samples were taken from 12 FH patients and 20 healthy controls with a similar age, gender distribution, and body mass index. Plasma chemokine levels were determined in both groups in a fasting state and at 2, 4, 6, and 8 h after an OFLT using human cytokine m…

Anthropometric parameters and permanent remission of comorbidities 10 years after open gastric bypass in a cohort with high prevalence of super-obesity

Abstract Background and aim Roux-en-Y gastric bypass (RYGB) is an effective treatment for weight loss in patients with morbid obesity. However, few studies have assessed its long-term efficacy in super-obese patients. The study objective was to analyse the long-term effectiveness of RYGB and its effect on improvement of comorbidities after 10 years of follow-up, and to compare the results depending on baseline BMI ( 2 vs ≥50 kg/m 2 ). Patients and methods A retrospective study was conducted in 63 patients referred for RYGB with a 10-year or longer follow-up period. Mean BMI before surgery was 55 kg/m 2 . Results Mean BMI decreased to 38.1 kg/m 2 at 10 years of follow-up. The success rates a…

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients

Abstract HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each interventi…

Severe, long-term hypoglycemia induced by co-trimoxazole in a patient with predisposing factors

Influencia de las mutaciones HF Valencia 1 y 2 del gen del receptor de LDL sobre la respuesta terapéutica a simvastatina en sujetos con hipercolesterolemia familiar heterocigota caracterizada molecularmente

Fundamento Analizar si el diagnostico molecular de la hipercolesterolemia familiar (HF) ayuda apredecir la respuesta terapeutica a simvastatina, en una poblacion mediterranea del sur de Europa. Sujetos y metodo Hemos estudiado la respuesta terapeutica en 27 sujetos con diagnostico genetico de HF (11 varones) pertenecientes a 8 familias con HF, seleccionadas por muestreo aleatorio entre 30 familias con HF con diagnostico molecular, en un estudio de intervencion sin grupo control con 20 mg/dia de simvastatina. Comparamos las caracteristicas clinicobiologicas entre sujetos clasificados como HF mutaciones nulas (HF Valencia 1 y Valencia 2; n = 11) o HF mutaciones no nulas (n = 16) en situacion …

Insulin resistance and oxidative stress in familial combined hyperlipidemia.

Oxidative stress is associated with atherosclerosis. Familial combined hyperlipidemia (FCH) is considered as a human model of primary dyslipidemia and atherosclerosis frequently associated with insulin resistance (IR), but there are few data on its possible relation to oxidative stress. The objective of this study was to evaluate oxidative stress status using different markers in subjects with FCH assessing its possible correlation with anthropometric parameters and IR. This was a cross-sectional study. A cohort of 40 FCH patients (20 with IR (HOMAor=3.2) and 20 without IR (HOMA3.2)), and 20 healthy volunteers were included, all of them non-diabetic, normotensive and non-smokers. We measure…

Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia.

The study objective was to investigate the relationship of insulin resistance (IR) with the lipoprotein phenotype in familial combined hyperlipidemia (FCH). Thirty-seven FCH men diagnosed by clinical and biochemical criteria and classified as lipoprotein phenotype IIa (n = 9), IIb (n = 17), or IV (n = 11) were compared with a healthy control group of 30 men of similar age, body mass index (BMI), waist to hip ratio (WHR), and systolic and diastolic blood pressure. In all subjects, the plasma lipoprotein profile and baseline and post-oral glucose tolerance test (OGTT) glucose and insulin plasma values were measured. An intravenous glucose tolerance test was performed and IR was studied by the…

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the associa…

Efectos no hipoglucemiantes de las glitazonas

Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes

Background Type 1 diabetes mellitus (T1DM) patients display increased risk of cardiovascular disease (CVD) and are characterized by a diminished regulatory T (Treg) cell content or function. Previous studies have shown an association between decreased CDKN2A/2B/2BAS gene expression and enhanced CVD. In the present study the potential relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction and increased cardiovascular risk in T1DM patients was explored. Methods A cross-sectional study was performed in 90 subjects divided into controls and T1DM patients. Circulating leukocyte subpopulations analysis by flow cytometry, expression studies on peripheral blood mononuclear cel…

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause

Objective: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). Methods: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). Results: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels w…

Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation.

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-&alpha

Abdominal obesity, insulin resistance, and metabolic syndrome in a southern European population.

Background: Our objective was to investigate the relationship between abdominal obesity (AO), as measured by waist circumference (WC), insulin resistance (IR), and components of the metabolic syndrome (MS). Methods: A cross-sectional study was carried out with 283 subjects (130 males and 153 females aged 25–65 years) from a primary care outpatient clinic in Valencia (Spain) over a period of 1 year. Body mass index (BMI), waist circumference (WC), blood pressure (BP), total cholesterol, triglycerides, HDL-C, glucose, and insulin were measured by standard methods. IR was defined as HOMA-IR equal to or greater than 3.8. Results: The prevalence of IR was 39.6%. Subjects were divided into groups…

Síndrome metabólico: ¿cómo diagnosticarlo y cómo tratarlo?

El sindrome metabolico es el conjunto de alteraciones metabolicas y cardiovasculares que estan relacionadas con la resistencia a la insulina y la obesidad abdominal. Los componentes del sindrome metabolico se van instaurando progresivamente, y van aumentando en numero y gravedad con la edad; este hecho se relaciona con el grado de obesidad y el sedentarismo, entre otros factores. El diagnostico del sindrome metabolico es un problema debido al elevado numero de criterios utilizado por diferentes sociedades y grupos de expertos. El sindrome metabolico es un concepto integrador de gran importancia por su relacion o asociacion con un elevado riesgo de presentar enfermedades cardiovasculares y d…

Functional role of endothelial CXCL16/CXCR6-platelet-leucocyte axis in angiotensin II-associated metabolic disorders.

Aims Angiotensin-II (Ang-II) is the main effector peptide of the renin-angiotensin system (RAS) and promotes leucocyte adhesion to the stimulated endothelium. Because RAS activation and Ang-II signalling are implicated in metabolic syndrome (MS) and abdominal aortic aneurysm (AAA), we investigated the effect of Ang-II on CXCL16 arterial expression, the underlying mechanisms, and the functional role of the CXCL16/CXCR6 axis in these cardiometabolic disorders. Methods and results Results from in vitro chamber assays revealed that CXCL16 neutralization significantly inhibited mononuclear leucocyte adhesion to arterial but not to venous endothelial cells. Flow cytometry and immunofluorescence s…

Enfermedad renal crónica y dislipidemia

Resumen La enfermedad renal cronica (ERC) ha de ser considerada como una situacion de alto e incluso muy alto riesgo cardiovascular, ya que provoca un aumento de la mortalidad cardiovascular que va incrementandose a medida que progresa la enfermedad. Es preciso realizar un diagnostico precoz de la ERC junto con la adecuada identificacion de los factores de riesgo, al objeto de frenar su evolucion a estadios mas severos, evitar las complicaciones y retrasar, en lo posible, la necesidad de tratamiento sustitutivo renal. La dislipidemia es un factor de progresion de la ERC que aumenta el riesgo de desarrollo de aterosclerosis y sus complicaciones. Su adecuado control contribuye a reducir la el…

Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion

Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CX3CL1/CX3CR1 and CCL2/CCR2 chemokine axes. Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CX3CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-&alpha

Síndrome de apnea-hipopnea del sueño como causa de seudofeocromocitoma

Los feocromocitomas son tumores neuroendocrinos poco frecuentes cuya manifestacion mas caracteristica es la hipertension arterial. Su diagnostico se basa en la demostracion de un exceso de produccion de catecolaminas o de sus metabolitos, seguido de tecnicas de imagen para la localizacion tumoral. Sin embargo, hay situaciones en las que estas hormonas pueden estar elevadas sin que haya un feocromocitoma; por tanto, esto se trata de falsos positivos. En esos casos hablamos de seudofeocromocitoma. Presentamos el caso de un paciente con un nodulo suprarrenal y catecolaminas elevadas de forma repetida en orina de 24 h. Fue intervenido quirurgicamente, pero a pesar de ello persistian las alterac…

Hipertiroidismo en el anciano

. Ademas, existe cierta tendencia a infrautilizar los recursos terapeuticos y preventivos en los ancianos. Las enfermedades tiroideas son muy prevalentes en el anciano, pero su diagnostico y tratamiento difiere de los estandares establecidos en la poblacion de mediana edad 5 , debido a las modificaciones que se producen con el envejecimiento, que conducen a cambios morfologicos y funcionales del tiroides que dificultan la interpretacion de las pruebas diagnosticas. A estos cambios se unen las alteraciones que sobre la funcion tiroidea tienen otras enfermedades intercurrentes, no tiroideas, muy frecuentes entre los ancianos, y las interacciones farmacologicas. Ademas, en el anciano debemos t…

PAI-1 Levels are Related to Insulin Resistance and Carotid Atherosclerosis in Subjects with Familial Combined Hyperlipidemia

Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (…

A study of insulin resistance using the minimal model in nondiabetic familial combined hyperlipidemic patients.

The presence of insulin resistance in 20 male nondiabetic patients with familial combined hyperlipidemia (FCH) and 20 controls of similar age and body mass index (BMI) was investigated using the minimal model method modified by the administration of insulin and an oral glucose tolerance test. The peripheral sensitivity of insulin, expressed as the insulin sensitivity index (Si), was 1.91 ± 1.05 and 2.86 ± 1.19 × 10−4 · min−1 · mU/L in FCH patients and controls, respectively (P < .01), and the corresponding value for the peripheral utilization of glucose independently of insulin (Sg) was 1.70 ± 1.13 in FCH patients and 2.35 ± 0.60 × 10−2 · min−1 in controls (P < .02). In the FCH group, the S…

Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration

Abstract Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardia…

Inhibición de la proproteína convertasa subtilisina/kexina tipo 9 en el tratamiento de la hipercolesterolemia

Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched b…

Changes in CDKN2A/2B expression associate with T-cell phenotype modulation in atherosclerosis and type 2 diabetes mellitus.

Previous studies indicate a role of CDKN2A/2B/2BAS genes in atherosclerosis and type 2 diabetes mellitus (T2DM). Progression of these diseases is accompanied by T-cell imbalance and chronic inflammation. Our main objective was to investigate a potential association between CDKN2A/2B/2BAS gene expression and T cell phenotype in T2DM and coronary artery disease (CAD) in humans, and to explore the therapeutic potential of these genes to restore immune cell homeostasis and disease progression. Reduced mRNA levels of CDKN2A (p16Ink4a), CDKN2B (p15Ink4b), and CDKN2BAS were observed in human T2DM and T2DM-CAD subjects compared with controls. Protein levels of p16Ink4a and p15Ink4b were also dimini…

Hiperlipidemia familiar combinada, síndrome metabólico y enfermedad cardiovascular

Se estudia la relacion entre sindrome metabolico (SM) e infarto agudo de miocardio (IAM) en la hiperlipidemia familiar combinada (HFC). Se comparan 20 sujetos varones con HFC supervivientes a IAM con otras 2 series de sujetos emparejados por edad e indice de masa corporal (IMC): 20 individuos con HFC que no han presentado IAM y 20 controles sanos. Se determinaron los lipidos, la glucosa y la insulina en plasma y la presencia de SM definido por criterios de la Organizacion Mundial de la Salud (OMS) y National Cholesterol Education Program-Adults Treatment Panel (NCEP-ATP-III). El SM definido por criterios OMS se encontro en 19 sujetos con HFC e IAM, en 11 sujetos con HFC sin IAM y en 6 contr…

Insulin resistance in patients with familial combined hyperlipidemia and coronary artery disease.

The minimum model modified by the administration of insulin provides an objective and relatively easily measured index of peripheral sensitivity to insulin which was significantly lower (p <0.02) in familial combined hyperlipidemia (FCH) with ischemic heart disease (IHD) than in FCH without IHD and in control subjects (1.2 +/- 0.6, 1.9 +/- 1.0, 2.9 +/- 1.2 x 10(-4) mU/L/ min, respectively). In patients with FCH, insulin resistance explains, at least in part, their metabolic alterations (hypertension, abnormal glucose tolerance, hyperinsulinemia) and elevated IHD.

La cintura hipertrigliceridémica

La definicion clinica de obesidad abdominal esta en revision. En la sociedad occidental se define clinicamente por el aumento del perimetro o diametro de la cintura, considerando patologico cuando es ≥ 94 cm en el hombre o ≥ 80 cm en la mujer. El aumento de la cintura es un parametro fundamental par definir el sindrome metabolico y se correlaciona con hipertrigliceridemia, que es la alteracion metabolica mas precoz y consistente del sindrome metabolico. La prevalencia de la obesidad abdominal o cintura patologica y su asociacion a hipertrigliceridemia y el resto de las alteraciones metabolicas relacionadas esta aumentando en las sociedades occidentales y en los paises en vias de desarrollo.…

Absence of CCR3 receptor accelerates atherosclerosis in apoE-/- mice

Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism.

OBJECTIVE—To identify a reliable yet simple indirect method for detection of insulin resistance (IR). RESEARCH DESIGN AND METHODS—A total of 65 subjects (44 men and 21 women aged 30–60 years) were selected by a simple random sampling method. Inclusion criteria were voluntary participation from staff and hospital personnel, absence of abnormal glucose tolerance, and normal results of lipid profile and basic blood chemistry. A blood sample was taken after a 12-h overnight fast to determine plasma lipid, glucose, and insulin levels. An intravenous glucose tolerance test with administration of insulin after 20 min and extraction of multiple blood samples for glucose and insulin measurements and…

Plasma homocysteine levels are independently associated with the severity of peripheral polyneuropathy in type 2 diabetic subjects.

Peripheral polyneuropathy (PN) is a frequent complication of diabetes. However, mechanisms underlying the development of PN are multifactorial and not well understood. Our aim was to examine the association of plasma homocysteine (Hcy) with the prevalence and grade of peripheral PN in patients with type 2 diabetes (T2DM). We studied a cohort of 196 subjects with T2DM classified according to the grade of PN (Neuropathy Disability Score, NDS). Subjects with the highest grade of PN were older and had significantly increased levels of creatinine, microalbuminuria, HbA1c, and plasma Hcy compared to the other two groups. The differences in plasma Hcy values were maintained after correcting for co…

A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH) is a genetic disorder characterized by increased low-density lipoprotein (LDL)-cholesterol levels, leading to high risk of premature cardiovascular disease. More than 900 mutations in LDL receptor, six in APOB and 10 in PCSK9 have been identified as a cause of the disease in different populations. All known mutations in PCSK9 causing hypercholesterolemia produce an increase in the enzymatic activity of this protease. Up to now, there are data about the implication of PCSK9 in ADH in a low number of populations, not including a Spanish population.The objective of the study was to study the prevalence of PCSK9 mutations in ADH Spanish population.W…

Dislipidemia aterogénica 2019. Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis

Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity.

Aims To evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses. Methods We included 20 subjects with abdominal obesity (waist circumference > 102 cm for men and > 88 cm for women) and 20 healthy lean controls (waist circumference < 102 cm for men and < 88 cm for women). After 12 hours of fasting we performed a standardized fat load test (0–8 hours) with supracal® (50 g/m2). We determined metabolic parameters, oxidized and reduced glutathione, and malondialdehyde. Results In…

Arteriosclerosis carotídea subclínica en pacientes con hiperlipidemia familiar combinada. Evolución tras dos años de tratamiento con dosis altas de atorvastatina

Resumen Fundamento y objetivo La hiperlipidemia familiar combinada (HFC) es un modelo genetico de dislipidemia aterogenica con insulinorresistencia y cardiopatia isquemica precoz. Nuestro objetivo fue evaluar la presencia de alteraciones a nivel carotideo, como marcador de arteriosclerosis sistemica, en sujetos con HFC, y valorar el efecto del tratamiento con 80 mg de atorvastatina diarios durante 2 anos sobre el grosor de la placa de ateroma. Sujetos y metodos Estudiamos 100 sujetos con HFC sin diabetes en prevencion primaria reclutados consecutivamente. Se determinaron parametros clinicos y bioquimicos, y se realizo ecografia carotidea. En los sujetos con placa de ateroma se inicio tratam…

Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia

Aims To assess the relationship of the lipid profile to coronary heart disease in a group of heterozygous familial hypercholesterolaemic subjects with similar age, sex, body mass index, prevalence of angiotensin converting enzyme DD genotype and type of low density lipoprotein receptor mutation. Methods and Results A total of 66 molecularly defined heterozygous familial hypercholesterolaemic subjects, 33 of whom had coronary heart disease, were studied. Clinical features, cardiovascular risk factors and lipid parameters were compared in both groups. Familial hypercholesterolaemic patients with coronary heart disease showed significantly lower values of mean plasma HDL cholesterol and a high…

Diabetes mellitus tipo 2: nuevos tratamientos

Resumen Se revisan los efectos beneficiosos y los problemas relacionados con los farmacos hipoglucemiantes tradicionales y se analizan los nuevos medicamentos de esta clase relacionados con el efecto incretina: analogos del peptido similar al glucagon tipo 1 e inhibidores de las dipeptidil peptidasas tipo 4. Ambos producen, de forma dependiente de la glucosa, una reduccion de la glucemia, no se relacionan con la hipoglucemia y no aumentan el peso. Otro nuevo grupo son los inhibidores del cotransportador sodio-glucosa tipo 2, que disminuyen la glucemia con bajo riesgo de hipoglucemia y con discreta perdida de peso. Los efectos beneficiosos a largo plazo y la prevencion cardiovascular no esta…