Peroxidación lipídica y factores de riesgo cardovascular

INTRODUCCIÓN: La lesión más incipiente que ha sido descrita en la patogénesis de la arteriosclerosis es la estría grasa. En este proceso los monocitos y los macrófagos juegan un papel muy importante. Los macrófagos no poseen receptores para las LDL negativas, sin embargo son capaces de reconocer las LDL modificadas a través del receptor scraveger. Ello provocará la entrada masiva de ésteres de colesterol en el interior de la célula, al no estar sujeta a ningún sistema de control, originando la formación de las células espumosas.De entre las diversas modificaciones que puede sufrir la partícula LDL, la oxidación es de todas ellas la más importante. Se ha podido comprobar un incremento en la susceptibilidad a oxidarse las LDL en pacientes con factor de riesgo coronario.OBJETIVOS: 1- Estudiar los niveles de peroxidación lipídica en plasma y en la fracción LDL en un grupo de población general y en sujetos con factores de riesgo coronario. 2- Estudiar los niveles de peroxidación lipídica en plasma y en la fracción LDL en pacientes hipercolesterolémicos. 3- Valorar las modificaciones de la peroxidación lipídica en plasma y en la fracción LDL en los pacientes hipercolesterolémicos tratados con probucol. 4- Estudiar los niveles de peroxidación lipídica en plasma y en la fracción LDL en pacientes diabéticos. 5- Estudiar los niveles de peroxidación lipídica en plasma en pacientes con obesidad mórbida. 6- Valorar los cambios en los niveles de peroxidación lipídica en plasma inducidos por una dieta muy baja e calorías. 7- Valorar los niveles de peroxidación lipídica en plasma y en la fracción LDL en relación a la edad y por último valorar los niveles de peroxidación lipídica en plasma y en la fracción LDL en relación al consumo de tabaco.MATERIAL Y MÉTODOS : Se seleccionaron un total de ochenta y tres pacientes (37&#9794; y 46&#9792;) con edades comprendidas entre los veintitrés y los sesenta y cuatro años, que acudían a control a la Unidad de Lípidos y de Enfermedades Metabólicas del Hospital de "Sant Joan de Reus". Estos pacientes estaban afectos de hipercolesterolemia aislada (n=33), diabetes tipo II (n=25) y obesidad mórbida (n=25).Asimismo, se reclutaron un total de noventa y tres individuos de la población sana (58&#9794; y 35&#9792;) con edades comprendidas entre los diecisiete y los ochenta y ocho años. Para su posterior estudio fueron divididos en relación a la edad (menores de 30, entre 30 y 64 y mayores de 65), ellos a su vez fueron estudiados en relación a su hábito tabáquico.Se incluyeron hipercolesterolémicos con niveles de colesterol en plasma > 6.5 mmol/L y niveles de triglicéridos Las pacientes con obesidad mórbida fueron hospitalizadas durante un periodo de veintiún días, durante los cuales fueron sometidas a una dieta muy baja en calorías e hiperproteica (VLCD) (MODIFAST). Se obtuvieron muestras sanguíneas al inicio y al finalizar dicho periodo.Se elaboró una historia clínica y exploración física completa, se determinaron los valores lipídicos y las fracciones lipoproteicas así como los valores de peroxidación lipídica en plasma y en a fracción LDL a todos los individuos incluidos en el estudio.RESULTADOS: En los pacientes hipercolesterolémicos observamos un descenso significativo en los niveles de colesterol total y colesterol LDL (15 y 13%) y (14 y 10%) respectivamente tras las 12 y 24 semanas de haber iniciado el tratamiento (pEn el grupo de pacientes diabéticos el nivel de colesterol en plasma fue de 5.28±0.82 y de triglicéridos 1.62±2.03, no apreciándose diferencias significativas en relación al grupo control de población sana. Sin embargo, los niveles de oxidación en plasma en diabéticos fue 6.89±1.53 y en el grupo control fue 5.14±1.74 (pEn el grupo de pacientes con obesidad mórbida normolipémicos observamos, al comparar el periodo de pre-dieta con el post-dieta, un descenso (pEl grupo de población sana de mayor edad presentó niveles de colesterol en plasma y colesterol HDL superiores a los otros grupos de forma significativa (p En el grupo de población sana no fumadora, los valores lipídicos fueron superiores a los fumadores aunque sin diferencias a excepción de los triglicéridos con una p De las diferentes correlaciones estudiadas solamente vimos una correlación positiva entre el colesterol plasmático y la oxidación en plasma en el grupo de varones fumadores y entre la edad y los niveles de oxidación en plasma y en la fracción LDL en el grupo de población sana. CONCLUSIONES: 1- Los sujetos con factores de riesgo vascular estudiados por nosotros, presentaron niveles de oxidación lipídica superiores al grupo control. 2- Los pacientes hipercolesterolémicos presentaron niveles de oxidación lipídica en plasma y en la fracción LDL superiores en un 33% y un 32% (p65 años presentaron niveles de oxidación lipídica en plasma y en LDL superiores en un 35% y un 30% respectivamente a los sujetos de edad entre los 30-64 años. Los varones 65 años, aunque en LDL la oxidación fue superior. 7- Los varones fumadores presentaron niveles de oxidación lipídica en LDL, significativamente superiores al grupo de no fumadores en un 31%. En plasma estas diferencias no fueron significativas.We have analysed the plasma and LDL oxidation susceptibility in individuals with and without the presence od cardiovascular risk factors. OBJECTIVES: To study the lipid peroxidation levels in plasma and LDL fraction in subjects with and without DHD risk factors: Hipercholesterolemia, Obesity, Diabetis, Odl age and Tabacco. To study the modification induced in the lipid peroxidation levels in plasma and LDL in hypercholesterolemia subjects after Probucol treatment and in obese subjects after a very low calory diet. SUBJECTES AND METHODS: Were recruited 83 patients attending to the metabolic Unit of Sant Joan Hospital (33 hypercholesterolemia, 25 diabetic, 25 obese). As control group were recruited 93 apparenty healthy individuals. A complete lipoprotein profile was determined by ultracentrifugation in them all. Thiobarbituric acid reacting substances were measured inn plasma and LDL fraction. In the hypercholesterolemia patients similar measurement were also carried out after 3 and 6 month if Probucol treatment. In the morbide obesity patients TBARS were analysed after 4 weeks on a very calory diet. RESULTS: Hipercholesterolemia patients had a higher concentration of TBARS both in plasma and LDL that the normalcholesterolemia subjects (7.69±2.19 vs 5.14±1.74 p65 years respect to the 30-64 years group (8.09±1.30 vs 5.14±1.74), 30-64 years group (8.09±1.30 vs 5.14±1.74 p<0.01, 3.07±0.54 vs 2.19±0.54 p<0.01). TBARS and age were lineally correlated r:0.6543 p<0.01, r:0.5923 p<0.01, when smokers were excluded. Smokers had higher TBARS in plasma and LDL oxidation concentration tham non smokers (6.72±1.73 vs 6.03±1.96, 4.0±1.15 vs 2.74±0.86 p<0.01). CONCLUSIONS: Hypercholesteolemia, diabetis, morbide obesity, smoking and ageing are associated to increased plasma and LDL oxidability. This could be a mechanism to explain the increased CHD risk associated the this conditions. Probucol and weight lose tend to correct the susceptibility to oxidation

Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL : "Herniated" HDL, a common feature in diabetes

Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects

HDL Triglycerides: A New Marker of Metabolic and Cardiovascular Risk

While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL&ndash;triglyceride (HDL-TG) concentration is not well known. We aim to examine plasma HDL-TG concentrations, assessed by 1H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital. The presence of arteriosclerotic plaques was assessed by ultrasonography. A complete lipoprotein profile was performed by 1H-NMR (Liposcale test). HDL-TG was strongly positively correlated with total triglycerides, glycerol, and fatty liver index, while a strong negative correlation was observed with HDL-cholesterol (HDL-C) and HDL-particle number (HDL-P). HDL-TG was associated with all triglyceride-rich lipoprotein parameters and had an opposite association with HDL-C and HDL-P. It was also significantly correlated with circulating cholesterol ester transfer protein (CETP). HDL-TG concentrations were higher as metabolic syndrome components increased. HDL-TG was also higher with worsening glucose metabolism. Patients with carotid plaques also showed higher HDL-TG. In contrast to HDL-C, HDL-TG is directly associated with metabolism and arteriosclerotic vascular alterations. HDL-TG should be considered a biomarker of metabolic and cardiovascular risk and could be a marker of HDL dysfunction

Green synthesis of Ag nanoparticles using grape stalk waste extract for the modification of screen-printed electrodes

Peer Reviewe

Familial hypercholesterolemia in a European Mediterranean population—Prevalence and clinical data from 2.5 million primary care patients

Familial hypercholesterolemia (FH), the most frequent hereditary cause of premature coronary heart disease (CHD), is underdiagnosed and insufficiently treated. Objectives The objectives of the study were to estimate the prevalence of the FH phenotype (FH-P) and to describe its clinical characteristics in a Mediterranean population. Methods Data were obtained from the Catalan primary care system's clinical records database (Catalan acronym: SIDIAP). Patients aged >7 years with at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2,554,644) were included. Heterozygous FH-P and homozygous FH-P were defined by untreated low-density lipoprotein cholesterol plasma concentrations. The presence of cardiovascular diseases and risk factors was defined by coded medical records from primary care and hospital discharge databases. Results The age- and sex-standardized prevalence of heterozygous FH-P and homozygous FH-P were 1/192 individuals and 1/425,774 individuals, respectively. In the group aged 8 to 18 years, 0.46% (95% confidence interval: 0.41–0.52) had FH-P; overall prevalence was 0.58% (95% confidence interval: 0.58–0.60). Among patients with FH-P aged >18 years, cardiovascular disease prevalence was 3.5 times higher than in general population, and CHD prevalence in those aged 35 to 59 years was 4.5 times higher than in those without FH-P. Lipid-lowering therapy was lacking in 13.5% of patients with FH-P, and only 31.6% of men and 22.7 of women were receiving high or very high-intensity lipid-lowering therapy. Conclusion Prevalence of FH-P was higher than expected, but underdiagnosed and suboptimally treated, especially in women. Moreover, treatment started late considering the high CHD incidence associated with this conditio

Autosomal dominant hypercholesterolemia in Catalonia : Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting

Background: Autosomal dominant hypercholesterolemia (ADH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is estimated to be greatly underdiagnosed. The most cost-effective strategy for increasing ADH diagnosis is a cascade screening from mutation-positive probands. Objective: The objective of this study was to evaluate the results from 2008 to 2016 of ADH genetic analysis performed in our clinical laboratory, serving most lipid units of Catalonia, a Spanish region with approximately 7.5 million inhabitants. Methods: After the application of the Dutch Lipid Clinic Network (DLCN) clinical diagnostic score for ADH, this information and blood or saliva from 23 different lipid clinic units were investigated in our laboratory. DNA was screened for mutations in LDLR, APOB, and PCSK9, using the DNA-array LIPOchip, the next-generation sequencing SEQPRO LIPO RS platform, and multiplex ligation-dependent probe amplification (MLPA). The Simon Broome Register Group (SBRG) criteria was calculated and analyzed for comparative purposes. Results: A total of 967 unrelated samples were analyzed. From this, 158 pathogenic variants were detected in 356 patients. The main components of the DLCN criteria associated with the presence of mutation were plasma LDL cholesterol (LDLc), age, and the presence of tendinous xanthomata. The contribution of family history to the diagnosis was lower than in other studies. DLCN and SBRG were similarly useful for predicting the presence of mutation. Conclusion: In a real clinical practice, multicenter setting in Catalonia, the percentage of positive genetic diagnosis in patients potentially affected by ADH was 38.6%. The DLCN showed a relatively low capacity to predict mutation detection but a higher one for ruling out mutation

A Therapeutic Dendritic Cell-Based Vaccine for HIV-1 Infection

A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects

Familial hypercholesterolemia in a European Mediterranean population-Prevalence and clinical data from 2.5 million primary care patients

BACKGROUND: Familial hypercholesterolemia (FH), the most frequent hereditary cause of premature coronary heart disease (CHD), is underdiagnosed and insufficiently treated. OBJECTIVES: The objectives of the study were to estimate the prevalence of the FH phenotype (FH-P) and to describe its clinical characteristics in a Mediterranean population. METHODS: Data were obtained from the Catalan primary care system's clinical records database (Catalan acronym: SIDIAP). Patients aged >7 years with at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2,554,644) were included. Heterozygous FH-P and homozygous FH-P were defined by untreated low-density lipoprotein cholesterol plasma concentrations. The presence of cardiovascular diseases and risk factors was defined by coded medical records from primary care and hospital discharge databases. RESULTS: The age- and sex-standardized prevalence of heterozygous FH-P and homozygous FH-P were 1/192 individuals and 1/425,774 individuals, respectively. In the group aged 8 to 18 years, 0.46% (95% confidence interval: 0.41-0.52) had FH-P; overall prevalence was 0.58% (95% confidence interval: 0.58-0.60). Among patients with FH-P aged >18 years, cardiovascular disease prevalence was 3.5 times higher than in general population, and CHD prevalence in those aged 35 to 59 years was 4.5 times higher than in those without FH-P. Lipid-lowering therapy was lacking in 13.5% of patients with FH-P, and only 31.6% of men and 22.7 of women were receiving high or very high-intensity lipid-lowering therapy. CONCLUSION: Prevalence of FH-P was higher than expected, but underdiagnosed and suboptimally treated, especially in women. Moreover, treatment started late considering the high CHD incidence associated with this condition