A proposal to redefine familial combined hyperlipidaemia -- third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation.

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Hyperinsulinemia as a determinant of microalbuminuria in essential hypertension

OBJECTIVE To analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs. PATIENTS AND METHODS Forty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose-tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 +/- 7.0 mg/24 h), and as microalbuminuric…

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…

Requirements for claims of favorable effects on serum lipids by oral antidiabetic agents.

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…

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…

An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia.

An international panel of the International Atherosclerosis Society has developed a new set of recommendations for management of dyslipidemia. The panel identifies non-high density lipoprotein cholesterol (non-HDL-C) as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for higher risk subjects. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or r…

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

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…

Respiratory chain polymorphisms and obesity in the Spanish population, a cross-sectional study

ObjectiveTo study the association of genes involved in the mitochondrial respiratory chain (MRC) pathway with body mass index (BMI) and obesity risk.DesignThis work studies three cross-sectional populations from Spain, representing three provinces: HORTEGA (Valladolid, Northwest/Centre), SEGOVIA (Segovia, Northwest/centre) and PIZARRA (Malaga,South).SettingForty-eight single nucleotide polymorphisms (SNPs) from MRC genes were selected and genotyped by SNPlex method. Association studies with BMI and obesity risk were performed for each population. These associations were then verified by analysis of the studied population as a whole (3731 samples).ParticipantsA total of 3731 Caucasian indivi…

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…

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…

Ancel Keys (1904-2004)

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…

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…

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…

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…

Supresión del eje hipotálamohipofisario-suprarrenal por la exposición crónica a glucocorticoides de uso tópico. Presentación de dos casos clínicos

Presentamos 2 casos clinicos con psoriasis extensa en los que el mal uso prolongado de corticoides topicos indujo la supresion del eje hipotalamohipofisario- suprarrenal y, como consecuencia, una insuficiencia suprarrenal secundaria. Se comentan los mecanismos y los factores que pueden dar lugar a dicha supresion.

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…

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…

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…

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 …

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…

Reduced penetrance of autosomal dominant hypercholesterolemia in a high percentage of families: importance of genetic testing in the entire family.

Abstract Background Autosomal dominant hypercholesterolemias (ADHs) are characterised by increased plasma levels of total and LDL cholesterol, predisposing to premature atherosclerosis. ADHs comprise several diseases with undistinguishable phenotype, caused by mutations in different genes: LDLR, APOB and PCSK9. Genetic studies are usually performed in patients with altered cholesterol levels. However, some persons carrying pathogenic mutations are normocholesterolemic and there are no further studies about this subject. We have studied the frequency of families and individuals carrying ADH mutations who do not present the disease in Spanish population. Methods We have analysed genes known t…

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…

Clinical review: impact of statin substitution policies on patient outcomes.

Background. The increasing awareness of cost issues in health care has led to the increasing use of policy-driven substitution of branded for generic medications, particularly relative to statin treatment for cardiovascular diseases. While there are potential short-term health care savings, the consequences for primary care are under-researched. Our objective was to review data on intensive statin therapy and generic substitution in patients at high cardiovascular risk. Results. Current treatment guidelines for the prevention of cardiovascular disease are consistent in their recommendations regarding statin therapy and treatment targets. Clinical trials demonstrate that to reduce cardiovasc…

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…

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these clai…

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…

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…

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…

Statins and diabetes.

Lipid abnormalities play an important part in raising the cardiovascular risk in diabetic subjects. The main components of diabetic dyslipidemia are increased plasma triglycerides, low concentration of high-density lipoprotein cholesterol, preponderance of small, dense low-density lipoprotein, and excessive postprandial lipemia. Small, dense low-density lipoprotein, the elevation in remnant triglyceride-rich lipoprotein particles, and the low high-density lipoprotein are the most powerful atherogenic components. The coexistence of these three factors strongly aggravates the lipid accumulation in the arterial wall and the formation of atherosclerotic plaques. The position of diabetes in card…

Riesgo elevado de disfunción lipoproteica en la diabetes mellitus tipo 2

La diabetes tipo 2 contribuye a un elevado riesgo cardiovascular. Un componente importante de dicho riesgo puede atribuirse a la dislipidemia diabetica, una agrupacion de anomalias de los lipidos y las lipoproteinas plasmaticos que estan interrelacionadas metabolicamente. Sus principales caracteristicas son una elevacion de los trigliceridos, una reduccion de las lipoproteinas de alta densidad (HDL) y un aumento de las lipoproteinas de baja densidad (LDL) pequenas y densas, a lo que se denomina la “triada lipidica aterogenica”. La dislipidemia diabetica se asocia a resistencia a la insulina, obesidad visceral y contenido de grasa hepatica. La resistencia a la insulina esta relacionada con u…

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…

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

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).…

The lipid composition of red blood cells and their hemorheological behavior in patients with primary hyperlipoproteinemia

Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the R…

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…

Arteriosclerosis and other diseases in heads of government and its consequences for the population.

Abstract Heads of government with cerebrovascular arteriosclerosis and other diseases in key historical moments have led to decisions that have marked the destiny of countries not always in a beneficial direction. Severe diseases in political leaders in power have often been hidden from citiziens with the collaboration of personal physicians. The confidentiality of the patient-doctor relationship in special political circumstances should be re examined and subjected to debate. Legal provisions to ensure total transparency of medical information about the health of heads of government should be implemented. Transparency ensures the trust of citizens.

Weaning induces NOS-2 expression through NF-κB modulation in the lactating mammary gland: importance of GSH

Zaragozá, R; Miralles, VJ; Rus, AD; García, C; Carmena, R; García-Trevijano, ER; Barber, T; Pallardó, FV; Torres, L; Viña, JR. At the end of lactation the mammary gland undergoes involution, a process characterized by apoptosis of secretory cells and tissue remodelling. To gain insight into this process, we analysed the gene expression profile by oligonucleotide microarrays during lactation and after forced weaning. Up-regulation of inflammatory mediators and acute-phase response genes during weaning was found. Expression of IκBα (inhibitory κBα), a protein known to modulate NF-κB (nuclear factor-κB) nuclear translocation, was significantly up-regulated. On the other hand, there was a time-…

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…

Type 2 diabetes, dyslipidemia, and vascular risk: rationale and evidence for correcting the lipid imbalance.

Type 2 diabetes is an important cardiovascular risk factor. A significant component of the risk associated with type 2 diabetes is thought to be because of its characteristic lipid "triad" profile of raised small dense low-density lipoprotein levels, lowered high-density lipoprotein, and elevated triglycerides (TGs). Trials of statins and fibrates have included substantial numbers of patients with diabetes and indicate that lipid lowering reduces cardiovascular event rates in these patients. However, statins alone do not always address all the lipid abnormalities of diabetes. Fibrates, which have low affinity for peroxisome proliferator-activated receptor alpha (PPARalpha), improve most asp…

Intensive lipid lowering with atorvastatin in patients with coronary artery disease, diabetes, and chronic kidney disease

To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes, with and without chronic kidney disease (CKD). Following 8 weeks' open-label therapy with atorvastatin (10 mg/d), 10,001 patients with coronary artery disease were randomized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1, 1998, and December 31, 1999. Of 1501 patients with diabetes, renal data were available for 1431. Patients with CKD were defined as having a baseline estimated glomerular filtration rate (eGFR) below 60…

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.

Arteriosclerosis y otras enfermedades en líderes políticos y sus consecuencias para la población

Resumen La arteriosclerosis cerebrovascular y otras enfermedades de algunos lideres politicos en momentos historicos clave han facultado la toma de decisiones que han marcado el destino de sus paises. Muchas enfermedades graves de lideres politicos, antes y durante su permanencia en el poder, se han ocultado a la poblacion, y a ello han colaborado sus medicos personales presionados por su paciente. La confidencialidad de la relacion medico-enfermo en circunstancias politicas especiales debe ser motivo de reflexion y debate. Seria deseable promulgar disposiciones que impidiesen la ocultacion y garantizasen la total transparencia de los informes medicos sobre el estado de salud de los dirigen…

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…

The diabetogenic action of statins — mechanisms and clinical implications

Treatment with statins has transformed primary and secondary prevention of cardiovascular disease (CVD), including thrombotic stroke. Evidence-based data demonstrate the benefits and safety of statin therapy and help to guide clinicians in the management of populations at high risk of CVD. Nevertheless, clinical trials, meta-analyses and observational studies highlight a 10-12% increase in new-onset diabetes mellitus (NODM) among patients receiving statins. The risk further increases with intensive therapy and among individuals with known risk factors for NODM. Mechanisms underpinning this effect are not yet fully understood; however, Mendelian randomization studies suggest that they are re…

Different impacts of cardiovascular risk factors on oxidative stress.

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant…

Consommation de pommes de terre et risques de maladie cardiovasculaire

Resume Les atouts de la pomme de terre declinee sous ses nombreuses formes, auxquels s’ajoutent ses qualites nutritives et son faible cout, expliquent sa consommation importante en Occident. Il apparait indispensable de reflechir a la place et au role tenu par la pomme de terre dans le cadre d’un regime alimentaire sain, au vu de l’incidence croissante des maladies cardiometaboliques comme l’atherosclerose, l’obesite et le diabete, tres liees a l’alimentation et au mode de vie. Il est delicat, dans le cadre d’etudes menees sur l’homme, de distinguer le role specifique d’un aliment de base par rapport a un autre. Des travaux indiquent toutefois que les pommes de terre possedent des propriete…

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…

40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes

OBJECTIVE—The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes. RESEARCH DESIGN AND METHODS—A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of &amp;lt;130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years…

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 all-cause 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 coron…

Role of GSH in the modulation of NOS-2 expression in the weaned mammary gland

GSH delivery to the lactating mammary gland is essential for the maintenance of lactation as its decrease leads to apoptosis and involution of the mammary gland. In fact, it has already been demonstrated that some of the changes in gene expression found in the lactating mammary gland after forced weaning are reproduced in rats treated with buthionine sulphoximine to deplete GSH levels. An oligonucleotide microarray experiment would give us a better knowledge of the mRNA expression patterns during lactation and after weaning and the possible functions of GSH in the modulation of these events.

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…

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…

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…

Association of selected ABC gene family single nucleotide polymorphisms with postprandial lipoproteins: results from the population-based Hortega study.

The aim of the study was to determine the influence of twenty single nucleotide polymorphisms (SNPs) of the ABCA1, ABCG1, ABCG5 and ABCG8 genes on the plasmatic concentrations of total cholesterol (TC), HDL and LDL cholesterol (HDLc, LDLc) in the postprandial state with a representative Spanish Caucasian population (1473 individuals, 50.0% women, ages ranging 21-85 years). In men, subjects with the AA genotype of the ABCA1 rs2230806 (R219K) polymorphism were associated with increased plasma LDLc levels, while the ABCA1 haplotype, which included the rs2230806 A allele, was associated with higher TC and LDLc plasma concentrations. In women, significant relationships were found between rs18935…

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…

Treat-to-target versus dose-adapted statin treatment of cholesterol to reduce cardiovascular risk

Clinical guidelines should be based on the best available evidence and are of great importance for patient care and disease prevention. In this respect, the 2013 American College of Cardiology/American Heart Association report is highly appreciated and well-recognized. The report included critical questions concerning hypercholesterolaemia, but its translation into a clinical guideline initiated intense debate worldwide because of the recommendation to switch from a treat-to-target approach for low-density-lipoprotein-cholesterol to a statin dose-based strategy.

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 (…

Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: Study in two Spanish populations

Abstract Background ABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet. Objective Our objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations. Methods We grounded our investigation on two general population-based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21–85 years) a…

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…

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…

Dificultad en el tratamiento del hipertiroidismo por amiodarona: Presentación de un caso

La amiodarona puede alterar la función tiroidea en un 15-20% de los pacientes que la toman, dando lugar a hipotiroidismo o hipertiroidismo. La sobrecarga de yodo y la toxicidad directa sobre el tiroides inducida por amiodarona pueden provocar hipertiroidismo. Describimos un caso de tirotoxicosis grave por amiodarona que se diagnosticó buscando la causa que descompensó la cardiopatía de base del paciente, condicionando ésta el pronóstico y el manejo terapéutico. El tratamiento precisó un estrecho seguimiento y se basó en dosis elevadas de propiltiouracilo y dexametasona que no controlaron las consecuencias del hipertiroidismo a nivel cardiaco necesitando la tiroidectomia total. Creemos, con …

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.

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…

Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study

BACKGROUND: Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the metabolic syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study assessed whether intensive lowering of low-density lipoprotein cholesterol with high-dose atorvastatin therapy results in cardiovascular benefits for patients with both coronary heart disease and the metabolic syndrome. METHODS: The TNT study was a prospective, double blind, parallel-group trial done at 256 sites in 14 countries between April, 1998, and August, 2004, with a median follow-…

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…

High Intestinal Cholesterol Absorption Is Associated With Cardiovascular Disease and Risk Alleles in ABCG8 and ABO

Objectives This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). Background Plant sterol–enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. Methods The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorpt…

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…

Low physical activity and its association with diabetes and other cardiovascular risk factors: a nationwide, population-based study

Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM; ISCIII Ministerio de Ciencia e Innovacion); Ministerio de Sanidad y Consumo; Spanish Diabetes Society (SED)