El futuro de las necesidades en salud y la Atención Primaria

Este artículo intenta aportar una aproximación al futuro de las necesidades de salud en España y a sus determinantes, así como al papel de la Atención primaria de salud para afrontar ambas

Genetics of Hypercholesterolemia: Comparison Between Familial Hypercholesterolemia and Hypercholesterolemia Nonrelated to LDL Receptor

Severe hypercholesterolemia (HC) is defined as an elevation of total cholesterol (TC) due to the increase in LDL cholesterol (LDL-C) >95th percentile or 190 mg/dl. The high values of LDL-C, especially when it is maintained over time, is considered a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), mostly expressed as ischemic heart disease (IHD). One of the best characterized forms of severe HC, familial hypercholesterolemia (FH), is caused by the presence of a major variant in one gene (LDLR, APOB, PCSK9, or ApoE), with an autosomal codominant pattern of inheritance, causing an extreme elevation of LDL-C and early IHD. Nevertheless, an important proportion of serious HC cases, denominated polygenic hypercholesterolemia (PH), may be attributed to the small additive effect of a number of single nucleotide variants (SNVs), located along the whole genome. The diagnosis, prevalence, and cardiovascular risk associated with PH has not been fully established at the moment. Cascade screening to detect a specific genetic defect is advised in all first- and second-degree relatives of subjects with FH. Conversely, in the rest of cases of HC, it is only advised to screen high values of LDL-C in first-degree relatives since there is not a consensus for the genetic diagnosis of PH. FH is associated with the highest cardiovascular risk, followed by PH and other forms of HC. Early detection and initiation of high-intensity lipid-lowering treatment is proposed in all subjects with severe HC for the primary prevention of ASCVD, with an objective of LDL-C <100 mg/dl or a decrease of at least 50%. A more aggressive reduction in LDL-C is necessary in HC subjects who associate personal history of ASCVD or other cardiovascular risk factors

Sistema de desarrollo basado en Freescale Freedom FRDM-KL25Z con fines docentes

Sistema de Desarrollo basado en Freescale Freedom FRDM-KL25Z con fines docentes, es un proyecto realizado con el fin de obtener un sistema de desarrollo versátil y universal, que permita la realización de las prácticas de la asignatura Sistemas Electrónicos Programables (SEP) perteneciente al Grado de Ingeniería Electrónica y Automática de la Universidad de Zaragoza. El objetivo principal del proyecto es la realización de un sistema de desarrollo que nos posibilite la migración de las prácticas de SEP, realizadas actualmente sobre un microcontrolador de 8 bits, a un microcontrolador ARM Cortex M0+ de 32 bits. Debido a su mayor proliferación, amplia utilización, reducido precio, disponibilidad absoluta, bajo consumo y elevadas prestaciones. Un microcontrolador es un computador completo (microprocesador, E/S, memoria, otros periféricos), aunque de limitadas prestaciones, que está contenido en el chip de un circuito integrado programable y se destina a gobernar una sola tarea con el programa que reside en su memoria. La plataforma de desarrollo Freescale Freedom es un conjunto de herramientas de hardware y software para la evaluación y desarrollo. Es ideal para prototipado rápido de aplicaciones basadas en microcontroladores. La tarjeta Freescale Freedom KL25Z, modelo FRDM-KL25Z, es un diseño rentable y capaz con un microcontrolador Kinetis serie L, uno de los primeros microcontroladores de la industria construido sobre el núcleo ARM ® Cortex ™ M0+. FRDM-KL25Z puede utilizarse para evaluar dispositivos de la serie Kinetis L. Cuenta con un microcontrolador KL25Z128VLK, un dispositivo con una máxima frecuencia de operación de 48MHz, 128KB de memoria flash, un controlador USB, periféricos analógicos y digitales. La placa FRDM-KL25Z es compatible con el diseño de Arduino ™ R3. FRDM-KL25Z es la primera plataforma de hardware de Freescale con OpenSDA (sistema abierto estándar serie integrado y adaptador debugger). Este circuito ofrece varias opciones para comunicaciones series, programación flash y control de ejecución de depuración. El Sistema de Desarrollo basado en Freescale FRDM-KL25Z consta de una placa de periféricos universal, donde se implementan tanto los elementos ya desarrollados en las prácticas de SEP (pulsadores y LEDS de propósito general, display 7 segmentos, teclado, módulo LCD), como nuevos dispositivos electrónicos (memoria EEPROM serie, conversores ADC y DCA, potenciómetro digital, acelerómetro) y diversos sensores (temperatura, presión, humedad). Además de la placa de circuito impreso, se han realizado varias librerías en lenguaje C, sobre la herramienta de diseño CodeWarrior Development Studio (v10.6_SE), que permiten la comunicación de los periféricos con el sistema de desarrollo Freescale FRDM-KL25Z

ANGPTL3 gene variants in subjects with familial combined hyperlipidemia

Angiopoietin-like 3 (ANGPTL3) plays an important role in lipid metabolism in humans. Loss-of-function variants in ANGPTL3 cause a monogenic disease named familial combined hypolipidemia. However, the potential contribution of ANGPTL3 gene in subjects with familial combined hyperlipidemia (FCHL) has not been studied. For that reason, the aim of this work was to investigate the potential contribution of ANGPTL3 in the aetiology of FCHL by identifying gain-of-function (GOF) genetic variants in the ANGPTL3 gene in FCHL subjects. ANGPTL3 gene was sequenced in 162 unrelated subjects with severe FCHL and 165 normolipemic controls. Pathogenicity of genetic variants was predicted with PredictSNP2 and FruitFly. Frequency of identified variants in FCHL was compared with that of normolipemic controls and that described in the 1000 Genomes Project. No GOF mutations in ANGPTL3 were present in subjects with FCHL. Four variants were identified in FCHL subjects, showing a different frequency from that observed in normolipemic controls: c.607-109T>C, c.607-47_607-46delGT, c.835+41C>A and c.*52_*60del. This last variant, c.*52_*60del, is a microRNA associated sequence in the 3'UTR of ANGPTL3, and it was present 2.7 times more frequently in normolipemic controls than in FCHL subjects. Our research shows that no GOF mutations in ANGPTL3 were found in a large group of unrelated subjects with FCHL

Sleep duration and subclinical atherosclerosis: The Aragon Workers' Health Study

Background and aims: Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, and with heterogeneous findings. We evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities. Methods: We performed a cross-sectional analysis of 1968 men, 40–60 years of age, participating in the Aragon Workers' Health Study (AWHS). Duration of sleep during a typical work week was assessed by questionnaire. Coronary artery calcium scores (CACS) was assessed by computed tomography and the presence of carotid plaque and femoral plaque by ultrasound. Results: In fully adjusted models, the odds ratios (95% CI) for CACS >0 comparing sleep durations of =5, 6, and =8 h with 7 h were 1.34 (0.98–1.85), 1.35 (1.08–1.69) and 1.21 (0.90–1.62), respectively (p = 0.04). A similar U-shaped association was observed for CACS =100 and for CACS. The corresponding odds ratios for the presence of at least one carotid plaque were =5, 6, and =8 h with 7 h were 1.23 (0.88–1.72), 1.09 (0.86–1.38), and 0.86 (0.63–1.17), respectively (p = 0.31), and for the presence of at least one femoral plaque were 1.25 (0.87–1.80), 1.19 (0.93–1.51) and 1.17 (0.86–1.61), respectively (p = 0.39). Conclusions: Middle-aged men reporting 7 h of sleep duration had the lowest prevalence of subclinical coronary atherosclerosis as assessed by CACs. Our results support that men with very short or very long sleep durations are at increased risk of atherosclerosis

Pharmacological Primary Cardiovascular Prevention and Subclinical Atherosclerosis in Men: Evidence from the Aragon Workers' Health Study.

The objective of this study is to describe the profile of primary preventive treatment for cardiovascular disease in adult males and to analyze the association between treatment profile and subclinical atherosclerosis. We selected male workers who had undergone ultrasound imaging and had no previous history of cardiovascular disease (n = 2138). Data on the consumption of primary cardiovascular drugs from the previous year were obtained. We performed bivariate analyses to compare patient characteristics according to cardiovascular treatment and the presence of subclinical atherosclerosis, and logistic regression models to explore the association between these two variables. Among participants with no personal history of cardiovascular disease, subclinical atherosclerosis was present in 77.7% and 31.2% had received some form of preventive treatment. Of those who received no preventive treatment, 73.6% had subclinical atherosclerosis. Cardiovascular preventive treatment was associated only with CACS > 0 (odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.06-1.78). Statin treatment was associated with a greater risk of any type of subclinical atherosclerosis (OR, 1.73) and with CACS > 0 (OR, 1.72). Subclinical atherosclerosis existed in almost 75% of men who had no personal history of cardiovascular disease and had not received preventive treatment for cardiovascular disease

Effect of intensive LDL cholesterol lowering with PCSK9 monoclonal antibodies on tendon xanthoma regression in familial hypercholesterolemia

Background and aims: The effect of LDLc lowering with PCSK9 antibodies on tendon xanthomas (TX) is unknown. Methods: TX was measured in 24 heterozygous familial hypercholesterolemia (HeFH) cases and in 24 HeFH controls with or without PCSK9 inhibitors for at least one year. Results: Exposure to PCSK9 inhibitors in cases was 2.96 ± 1.33 years. LDLc decreased 80.8 ± 7.66% in cases and 56.9 ± 11.1% in controls. There was a decrease in maximum (-5.03%) and mean (-5.32%) TX in cases but not in controls (+3.97%, +3.16, respectively, p = 0.01). PCSK9 inhibitor treatment was independently associated with TX reduction. Conclusion: Addition of a PCSK9 inhibitor to statin and ezetimibe resulted in a greater decrease in LDLc and TX after 3 years of treatment

Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE

Background: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). Methods: The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides 90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison. Results: We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively). Conclusions: Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias

Work shift, lifestyle factors, and subclinical atherosclerosis in spanish male workers: A mediation analysis

(1) Background: Working night shifts has been associated with altered circadian rhythms, lifestyle habits, and cardiometabolic risks. No information on the potential association of working shift and the presence of atherosclerosis is available. The aim of this study was to quantify the association between different work shifts and the presence of subclinical atherosclerosis objectively measured by imaging. (2) Methods: Analyses were conducted on the baseline data of the Aragon Workers Health Study (AWHS) cohort, including information on 2459 middle-aged men. Categories of shift work included central day shift, rotating morning-evening or morning-evening-night shift, and night shift. The presence of atherosclerotic plaques was assessed by 2D ultrasound in the carotid and femoral vascular territories. Multivariable logistic models and mediation analysis were conducted to characterize and quantify the association between study variables. (3) Results: Participants working night or rotating shifts presented an overall worse cardiometabolic risk profile, as well as more detrimental lifestyle habits. Workers in the most intense (morning-evening-night) rotating shift presented higher odds of subclinical atherosclerosis (odds ratio: 1.6; 95% confidence interval: 1.12 to 2.27) compared to workers in the central shift, independently of the presence of lifestyle and metabolic risk factors. A considerable (21%) proportion of this association was found to be mediated by smoking, indicating that altered sleep-wake cycles have a direct relationship with the early presence of atherosclerotic lesions. (4) Conclusions: Work shifts should be factored in during workers health examinations, and when developing effective workplace wellness programs

High-quality intake of carbohydrates is associated with lower prevalence of subclinical atherosclerosis in femoral arteries: The AWHS study

Background and aims: High-quality of the carbohydrates consumed, apart from their total amount, appear to protect from cardiovascular disease (CVD). However, the relationship between the quality of carbohydrates and the early appearance of atherosclerosis has not yet been described. Our objective was to estimate the association between the quality of dietary carbohydrates and subclinical atherosclerosis in femoral and carotid arteries. Methods: Cross-sectional study of femoral and carotid atherosclerosis assessed using ultrasounds of 2074 middle-aged males, 50.9 (SD 3.9) years old, with no previous CVD, and pertaining to the Aragon Workers’ Health Study (AWHS) cohort. Food frequency questionnaires were used to calculate a carbohydrate quality index (CQI) defined as: consumption of dietary fiber, a lower glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The presence of plaques across four CQI intervals was studied using adjusted logistic regression models. Results: The CQI showed a direct inverse association with subclinical atherosclerosis in femoral territories. Participants with a higher consumption of high-quality carbohydrates (13–15 points) were less likely to have femoral plaques when compared with participants in the lowest index interval (4–6 points) (OR = 0.59; 95% CI = 0.39, 0.89; p = 0.005). No association was found between the CQI and the presence of subclinical atherosclerosis in carotid territories. A lower consumption of high-quality carbohydrates tended to be associated with a greater atherosclerosis extension, considered as the odds for having more affected territories (p = 0.011). Conclusions: Among middle-aged males, a high-quality intake of carbohydrates is associated with a lower prevalence of femoral artery subclinical atherosclerosis when compared with a lower consumption. Thus, indicating an early relationship between the quality of carbohydrates and the development of CVD. © 2021 The Author(s