Association of rs662799 and rs5070 genetic polymorphisms with hypertriglyceridemia and atherogenic dyslipidemia in pediatric patients in Southeast Mexico.

BACKGROUND AND AIMS: Triglycerides are the initiators of the metabolic changes that lead to atherogenic dyslipidemia (AD). The APOA5 and APOA1 genes are involved in the response and metabolism of serum lipids and lipoproteins, where single nucleotide polymorphisms (SNP) rs662799 (promoter region) and rs5070 (intronic region) have been associated with the susceptibility to dyslipidemia. Until now, few studies evaluate the association of these polymorphisms with the presentation of hypertriglyceridemia and AD among Mexican children. Therefore, the objective was to determine the association between rs662799 and rs5070 with hypertriglyceridemia and AD in a pediatric population of southeastern Mexico. MATERIALS AND METHODS: A case-control analysis was performed including 268 infants aged 2-16 years, anthropometric, clinical variables, and serum lipid profiles were analyzed. DNA was extracted from blood samples and genotyping of polymorphisms was executed with the TaqMan SNP genotyping assay. Allele and genotypic frequencies were calculated. For genetic association analysis, logistic regression models were fitted according to models of inheritance. RESULTS: The SNP rs662799 (C) was significantly associated with hypertriglyceridemia in the overdominant model (OR=3.89, p=0.001) and AD in the dominant model (OR=4.01, p=0.001). The SNP rs5070 (T) has a protective effect against hypertriglyceridemia in the additive risk model (OR=0.68, p=0.03). CONCLUSION: Polymorphism rs662799 was significantly associated with cases of hypertriglyceridemia and AD in minors in southeastern Mexico. On the other hand, rs5070 polymorphism was not associated with cases of hypertriglyceridemia or AD.

Chia seeds and chemical-elicited sprouts supplementation ameliorates insulin resistance, dyslipidemia, and hepatic steatosis in obese rats.

Chia seeds (CS) and sprouts are rich in bioactive compounds. This study aimed to assess the effects of germination and chemical elicitation (salicylic acid [SA]; hydrogen peroxide [H2 O2 ]) on proximate chemical, total phenolics compounds (TPC), non-extractable proanthocyanidins (NEPA), and carotenoids content of chia sprouts; besides, the effects of their supplementation on obesity-associated complications in rats fed with high-fat and fructose diet (HFFD) were evaluated. Protein, carbohydrate, TPC, NEPA, and carotenoids content were higher in sprouts than CS; elicitation enhanced TPC and carotenoids compared to non-elicited (NE) sprouts. CS, NE, and elicited chia sprouts ameliorated insulin resistance and dyslipidemia at the same level in HFFD-fed rats. NE and SA-chia sprouts exerted the biggest reduction in hepatic triglycerides, which could be partially related to inhibition of pancreatic lipase activity. In addition, SA elicitation induced the greatest effect on insulin levels and corporal weight. CS and their sprouts decreased obesity and its complication, mainly SA-elicited sprouts. PRACTICAL APPLICATIONS: The growing epidemic of non-communicable diseases such as diabetes and obesity has led to the search for prevention and treatment through lifestyle changes, including the consumption of foods rich in bioactive compounds, such as seeds and their sprouts. Since sprouts contain higher concentrations of bioactive compounds and nutrients than seed, germination is a natural alternative to produce ready-to-eat functional foods. Chemical elicitation is a strategy to increase even more the bioactivity of sprouts. CS has been recognized for its beneficial health effects ameliorating dyslipidemia and insulin resistance. This study demonstrates that elicitation, with SA and H2 O2 , during germination of CS, increases the nutrient and phytochemical content of sprouts, with beneficial effects on body weight gain, insulin resistance, dyslipidemia, and prevention of NAFLD progression in diet-induced obese rats. Therefore, chia sprouts, natural and elicited, may be used as potential nutraceutical foods for the prevention and treatment of obesity and its complications.

Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON.

BACKGROUND: Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM. METHODS: This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD. RESULTS: In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C < 1.4 mmol/L and an LDL-C reduction of at least 50%, > 75% achieved non-HDL-C < 2.2 mmol/L at the mean of weeks 10 and 12, and > 67% achieved ApoB < 65 mg/dL at week 12. CONCLUSIONS: Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.

The CNIC-polypill improves atherogenic dyslipidemia markers in patients at high risk or with cardiovascular disease: Results from a real-world setting in Mexico.

BACKGROUND: In many patients, the risk of cardiovascular (CV) events persists despite statin treatment and attaining target LDL-c levels. This residual risk is in part attributed to atherogenic dyslipidemia (AD). We studied the clinical effectiveness of the CNIC-polypill in improving the lipid profile, and lipid ratios and indices indicative of AD that are more accurate in predicting lipid-related CV risk. METHODS: Post-hoc analysis of a multicenter, observational, non-comparative, prospective registry in 533 patients in Mexico. We evaluated blood lipids at baseline (usual care) and after 12 months of treatment with the CNIC-polypill (Sincronium®), including total cholesterol (TC), triglycerides (TG), cholesterol low-density lipoproteins (LDL-c), cholesterol high-density lipoproteins (HDL-c), and cholesterol non-high-density lipoproteins (non-HDL-c). We also calculated and compared AD-related lipid ratios and indices, including remnant cholesterol (RC), Castelli's risk index-I (CRI-I), atherogenic index (AI), atherogenic coefficient (AC), a surrogate of insulin resistance (IRS), atherogenic index of plasma (AIP), and lipoprotein combined index (LCI). RESULTS: At 1 year of treatment, there was a significant reduction in the levels of TC (-22.6%), TG (-29.2%), LDL-c (-13.8%), and non-HDL-c (-29.2%) (all p < 0.001). The likelihood that patients attained their corresponding target LDL-c and TG levels was almost three-fold and seven-fold higher, respectively (p < 0.001). The values of the AD-related ratios RC, CRI-I, AI, AC, AIP, and LCI were all significantly lower (p < 0.001) after one year of treatment. CONCLUSIONS: In patients with or at high risk of CVD, one-year treatment with the CNIC-polypill significantly lowered lipid ratios indicative of AD compared to baseline.

Atherogenic dyslipidemia in Latin America: prevalence, causes and treatment. Consensus / Dislipidemia aterogénica en Latinoamérica: prevalencia, causas y tratamiento. Un consenso

Abstract: Atherogenic dyslipidemia (DA) is a poorly recognized entity in the current clinical practice guidelines. Due to the frequent lipid alterations associated with this metabolic abnormality in Latin America (LA), we organized a group of experts that has adopted the name of Latin American Association for the study of Lipids (ALALIP), to generate a document for analyzing in LA the prevalence of the lipid profile related to this condition, and to offer practical recommendations for its optimal diagnosis and treatment. Methodology: It was is selected a group of regional experts and, using a modified Delphi methodology, we conducted a comprehensive literature review, with emphasis on studies or reviews that had implications for LA. Subsequently developed a series of key questions about the epidemiology, pathophysiology, diagnosis, and treatment of the AD to be discussed by the group of experts. As a convention those recommendations that had 100% acceptance was consider unanimous; those with at least 80% as for consensus, and of disagreement, those with less than 80%. Results: Although there is no a global study on risk factors that has been made on the basis of a representative sample of the entire population of LA, the systematic analysis of the national health surveys and regional cohort studies based on local population sampling shows a consistent evidence of the high prevalence of the lipid abnormalities that define the AD. The prevalence of low levels of high density lipoprotein cholesterol (HDL-C) ranges from 34.1% (CESCAS I study) to 53.3% (LASO study), with different frequencies between men and women and the selected cut-off point. The prevalence of elevated triglycerides (TRG) varies from 25.5% (LASO study) to 31.2% (National Health Survey of Chile) being always more prevalent in men than in women. Only two studies report the prevalence of AD in LA: the National Health Survey of Mexico 2006 with an 18.3%, and a Venezuelan study that estimates the weighted prevalence of AD in 24.7%. There are multiple causes for these findings: an inadequate nutrition-characterized for high consumption of foods with a high caloric density and a high intake of cholesterol and trans fats-, a sedentary lifestyle, a high prevalence of obesity in the region, and possibly epigenetic changes that make our population more susceptible for having this abnormal lipid profile. Conclusions: Lipid abnormalities that define AD have a high prevalence in LA; the interaction between the style of living, the inheritance, and epigenetic changes possibly are its cause. Since they are considered as an important cause of residual cardiovascular risk, they must be diagnosed and treated actively as a secondary target after reaching the goal for low density lipoprotein-cholesterol (LDL-C). It is important to design a global study of risk factors in our region to let us know the true prevalence of AD and its causes, and to help us in the design of public policies adapted to our reality in a population and individual scale.

Resumen: La dislipidemia aterogénica (DA) es una entidad poco reconocida en las guías de práctica clínica actuales. Debido a las frecuentes alteraciones lipídicas asociadas a esta anomalía metabólica en América Latina (AL), hemos organizado un grupo de expertos que ha adoptado el nombre de Asociación Latinoamericana para el Estudio de Lípidos (ALALIP), para generar un documento en el que se analice la prevalencia en AL del perfil lipídico relacionado con esta afección y ofrecer recomendaciones prácticas para su óptimo diagnóstico y tratamiento. Metodología: Se seleccionó un grupo de expertos regionales y, utilizando una metodología Delphi modificada, se realizó una revisión bibliográfica exhaustiva, con énfasis en estudios o revisiones que tuvieran implicaciones para AL. Posteriormente se desarrolló una serie de preguntas clave sobre la epidemiología, la fisiopatología, el diagnóstico y el tratamiento de la DA, que fueron discutidas por el grupo de expertos. Como convención, las recomendaciones que tuvieron un 100% de aceptación fueron consideradas unánimes; aquellas con al menos el 80% como para el consenso, y de desacuerdo, aquellas con menos del 80%. Resultados: Aunque no existe un estudio global sobre los factores de riesgo que se haya realizado sobre la base de una muestra representativa de toda la población de AL, el análisis sistemático de las encuestas nacionales de salud y los estudios de cohortes regionales evidencian la alta prevalencia de las anormalidades lipídicas que definen la DA. La prevalencia de niveles bajos de colesterol de lipoproteínas de alta densidad (HDL-C) oscila entre el 34.1% (estudio CESCAS I) y el 53.3% (estudio LASO), con diferentes frecuencias entre hombres y mujeres y el punto de corte seleccionado. La prevalencia de triglicéridos elevados (TRG) varía de 25.5% (estudio LASO) a 31.2% (Encuesta Nacional de Salud de Chile) siendo siempre más prevalente en hombres que en mujeres. Sólo dos estudios informan la prevalencia de DA en AL: la Encuesta Nacional de Salud de México 2006 con un 18.3%, y un estudio venezolano que estima la prevalencia ponderada de la DA en 24.7%. Existen múltiples causas para estos hallazgos: una nutrición inadecuada -caracterizada por el alto consumo de alimentos con alta densidad calórica y un alto consumo de colesterol y grasas trans- un estilo de vida sedentario, una alta prevalencia de obesidad en la región y posiblemente cambios epigenéticos que hacen que nuestra población sea más susceptible a tener este perfil lipídico anormal. Conclusiones: Las anomalías lipídicas que definen la DA tienen una alta prevalencia en AL; la interacción entre el estilo de vida, la herencia, y los cambios epigenéticos posiblemente son su causa. Debido a que se consideran una causa importante de riesgo cardiovascular residual, deben ser diagnosticados y tratados activamente como un objetivo secundario después de alcanzar la meta para el colesterol de lipoproteína de baja densidad (LDL-C). Es importante diseñar un estudio global de los factores de riesgo en nuestra región para hacernos conocer la verdadera prevalencia de la DA y sus causas y ayudarnos en el diseño de políticas públicas adaptadas a nuestra realidad en una escala poblacional e individual.

Dislipidemia aterogénica en Latino América: prevalencia, causas y tratamiento / Atherogenic dislipidemia in Latin America: prevalence, causes and treatment

En las guías clínicas actuales, la dislipidemia aterogénica (DA) es una entidad escasamente atendida. Debido a las frecuentes alteraciones en los lípidos asociados a la DA en Latino América (LA), se organizó un grupo de expertos que se ha denominado Academia Latino Americana para el estudio de los Lípidos (ALALIP) para generar un documento con análisis de su prevalencia y ofrecer recomendaciones prácticas. Se utilizó la metodología Delphi modificada, con revisión comprensiva de la literatura con énfasis en aquellas publicaciones con implicaciones para LA. Subsecuentemente, se desarrollaron preguntas claves para ser discutidas. En LA no existe un estudio global sobre los factores de riesgo que representan a la totalidad de la población. El análisis sistemático de las encuestas nacionales de salud y de los estudios sistemáticos de cohorte muestran consistentemente una alta prevalencia de las anormalidades lipídicas que definen la DA. La concentración baja del colesterol unido a las lipoproteínas de alta densidad (C-HDL) varía entre 34,1% a 53,3% y la de triglicéridos (TG) elevados del 25,5% al 31,2%, con mayor prevalencia entre los hombres. Múltiples causas se han reconocidos, como alta ingesta de alimentos de mayor densidad calórica, contenido de colesterol, grasas trans, sedentarismo y cambios epigenéticos. La DA bien puede ser tratada con los cambios terapéuticos del estilo de vida (CTEV) con incremento en la actividad física, ejercicio regular y dieta baja en carbohidratos y alta en ácidos grasos poliinsaturados, tales como los ácidos grasos omega-3 como intervención primaria. De ser necesario, esta estrategia sera suplementada con terapia farmacológica como la monoterapia con estatinas o la combinación de fibratos/ácidos grasos omega-3. Las anormalidades lipídicas que definen la DA tienen una elevada prevalencia en LA; su interacción con un estilo de vida no saludable, herencia y cambios epigenéticos están ligados a sus posibles causas. La DA es una causa importante de riesgo cardiovascular residual (RCVR) que debe ser diagnosticada y tratada. Es importante y necesario diseñar un estudio global de factores de riesgo en LA para conocer la real prevalencia de la DA.

In the current clinical guidelines, atherogenic dyslipidemia (AD) is a poorly recognized entity. Due to the frequent lipid alterations associated with AD in Latin America (LA), we organized a group of experts named Latin American Academy for the study of Lipids (ALALIP), to generate a document for analyzing its prevalence and to offer practical recommendations. Using the Delphi methodology, we conducted a comprehensive literature review, with emphasis on those publications with implications for LA. Subsequently we developed key questions to be discussed. In LA there is no a global study on risk factors that represent the entire population. The systematic analysis of national health surveys and regional cohort studies showed a consistent high prevalence of the lipid abnormalities that define AD. Low high density lipoprotein cholesterol (HDL-C) ranges from 34.1% to 53.3% and elevated triglycerides (TG) from 25.5% to 31.2%, more prevalent in men. There are multiple causes: high consumption of foods with a high caloric density, cholesterol and trans fats, sedentary lifestyle and epigenetic changes. AD must be well treated with therapeutic changes in lifestyle with increased in physical activities, regular exercise and a diet with a low proportion of carbohydrates y rich in poliunsatured fatty acid, such as omega-3 fatty acid as primary intervention. If needed, this strategie must be supplemented with pharmacological therapies such as monotherapy with statins or a combination of fibrates plus omega-3.fatty acid. Lipid abnormalities that define AD have a high prevalence in LA; the interaction between non-healthy lifestyle, inheritance and epigenetic changes, possibly are its cause. AD is an important cause of cardiovascular residual risk (CVRR), that must be diagnosed and treated. It is important and neccesary to design a global study of risk factors in LA to know the true prevalence of AD.

Dislipidemia aterogénica en latino américa: prevalencia, causas y tratamiento / Atherogenic dyslipidemia in Latin America: prevalence, causes and treatment

En las guías clínicas actuales, la dislipidemia aterogénica (DA) es una entidad no muy atendida. Debido a las frecuentes alteraciones en los lípidos asociados a la DA en Latino América (LA). Métodos: organizamos un grupo de expertos denominado Academia Latino Americana para el estudio de los Lípidos (ALALIP) para así generar un documento con análisis de su prevalencia y recomendaciones terapéuticas prácticas. Se utilizó la metodología Delphi modificada, con una revisión integral de la literatura y énfasis en las publicaciones con implicaciones para LA. Subsecuentemente, desarrollamos preguntas claves para ser discutidas. Resultados: En Latinoamérica (LA) no existe un estudio global sobre los factores de riesgo que representan a la totalidad de la población. El análisis sistemático de las encuestas nacionales de salud y de los estudios sistemáticos de cohorte muestran consistentemente una alta prevalencia de las anormalidades lipídicas que definen la DA. La concentración baja del colesterol unido a las lipoproteínas de alta densidad (C-HDL) varía entre 34,1% a 53,3% y la de triglicéridos (TG) elevados del 25,5% al 31,2%, con mayor prevalencia entre los hombres. La DA bien puede ser tratada con los cambios del estilo de vida (CTEV) como ncremento en laactividad física, dieta baja en carbohidratos y alta en ácidos grasos poliinsaturados, tales como los ácidos grasos omega-3 como intervención primaria. De ser necesario, esta estrategia sera suplementada con terapia farmacológica como la monoterapia con estatinas o la combinación de fibratos/ácidos grasos omega-3. Conclusiones: Las anormalidades lipídicas que definen la DA tienen una elevada prevalencia en LA; su interacción con un estilo de vida no saludable, herencia y cambios epigenéticos están ligados a sus posibles causas. La DA es una causa importante de riesgo cardiovascular residual (RCVR) que debe ser diagnosticada y tratada. Es importante y necesario diseñar un estudio global de factores de riesgo en LA para conocer la real prevalencia de la DA(AU)

In the current clinical guidelines, atherogenic Med Interna (Caracas) 2017; 33 (3): 121 - 139 Dislipidemia Aterogénica en Latino América: Prevalencia, causas y tratamiento Carlos I. Ponte-N, Jesús E. Isea-Pérez, Alberto J. Lorenzatti, Patricio López-Jaramillo, Fernando Stuardo Wyss-Q, Xavier Pintó, Fernando Lanas, Josefina Medina, Livia T. Machado-H, Mónica Acevedo, Paola Varleta Alfonso Bryce, Carlos Carrera, Carlos Ernesto Peñaherrera, José Ramón Gómez-M, Alfredo Lozada, Alonso Merchan-V, Daniel Piskorz, Enrique Morales, María Paniagua, Félix Medina-Palomino, Raúl Alejandro Villar-M, Leonardo Cobos, Enrique Gómez-Álvares, Rodrigo Alonso, Juan Colan, Julio Chirinos, Jofre Lara, Vladimir Ullauri, Ildefonso Arocha Documento de la posición de expertos de la Academia Latino Americana para el estudio de los Lípidos (ALALIP) y avalado por la Sociedad Interamericana de Cardiología (SIAC), Sociedad Sur Americana de Cardiología (SSC), el Colegio Panamericano de Endotelio (CPAE) y la Sociedad Internacional de Aterosclerosis (IAS). Publicado en conjunto con las Revistas de la Sociedad Venezolana de Medicina Interna y de la Sociedad Venezolana de ndocrinología y Metabolismo. dyslipidemia (AD) is a poorly recognized entity. Due to the frequent lipid alterations associated with AD in Latin America (LA), we organized a group of experts named Latin American Academy for the study of Lipids (ALALIP), to generate a document to analize it´s prevalence and to offer practical recommendations. Methodology: Using the Delphi methodology, we conducted a comprehensive literature review, with emphasis on those publications with implications for LA. Subsequently we developed key questions to be discussed. Results: In LA There is no a global study on risk factors that represent the entire population. The systematic analysis of national health surveys and regional cohort studies showed a consistent high prevalence of the lipid abnormalities that define AD. Low high density lipoprotein cholesterol (HDL-C) ranges from 34.1% to 53.3% and elevated triglycerides (TG) from 25.5% to 31.2% more prevalent in men. There are multiple causes: high consumption of foods with a high caloric density, cholesterol and trans fats, sedentary lifestyle and epigenetic changes. AD must be well treated with therapeutic changes in lifestyle with increase in physical activities, regular exercise and a diet with a low proportion of carbohydrates and rich in poliunsatured fatty acid, such as omega-3 fatty acids as primary intervention. If needed, this strategy must be supplemented with pharmacological therapies such as monotherapy with statins or a combination of fibrates plus omega-3. fatty acid. conclusions: Lipid abnormalities that define AD have a high prevalence in LA; the interaction between non-healthy lifestyle, inheritance and epigenetic changes, possibly are the cause. AD is an important cause of cardiovascular residual risk (CVRR), that must be diagnosed and treated It is important and necesary to design a global study of risk factors in LA to know the true prevalence of AD(AU)