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Background: The objective of this research is to evaluate the efficacy and safety of drugs in the residual risk in any of its three components: lipid, inflammatory and thrombotic risk. Methods: A systematic review was conducted of randomized clinical trials that included as a primary outcome, at least one of the conditions related to atherosclerotic cardiovascular disease. The databases used were PUBMED/MEDLINE, Scopus and ClinicalTrials.gov. The risk of bias of the studies was assessed using the Risk of Bias 2 tool. Results: and discussion: 18 studies were included in the analysis. Half of the studies had low risk of bias or some concerns. Several drugs were effective in reducing the primary outcome: ethyl eicosapentaenoeic acid (17.2 % E-EPA versus 22 % placebo HR: 0.75; 95 % CI 0.68-0.83; p < 0.001), colchicine in stable coronary artery disease (6.8 % vs placebo 9.6 %, HR 0.59, 95 % CI 0.57-0.83; p < 0.001), Canakinumab (150 mg vs placebo ARR 15 %, HR 0.85, 95 % CI 0.74-0.98; p = 0.021) and Rivaroxaban with Aspirin in stable atherosclerotic disease (4.1 % versus aspirin 5.4 %, HR 0.76, 95 % CI 0.66-0.86, P < 0.001). Serious adverse events did not differ between study groups, except for a higher rate of bleeding with the use of combination antithrombotic therapy. Conclusion: The residual risk can be reduced through the use of different drugs that act by modifying atherogenic lipid levels, modulating inflammatory pathways and the risk of thrombosis, with an acceptable safety profile in most studies.

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Resumen La inflamación es un factor patogénico importante para el desarrollo de la enfermedad cardiovascular aterosclerótica. Actualmente, el biomarcador utilizado con mayor frecuencia que refleja la inflamación sistémica es la proteína C reactiva (PCR), una proteína de fase aguda producida principalmente por los hepatocitos bajo la influencia de la interleucina 6, la interleucina 1 beta y el factor de necrosis tumoral. La evidencia proveniente de estudios epidemiológicos ha demostrado una fuerte asociación entre las concentraciones elevadas de PCR en suero o plasma y la incidencia de un primer evento cardiovascular (incluido infarto agudo de miocardio, accidente vascular cerebral isquémico y muerte cardíaca súbita) en la población general, así como la recurrencia de eventos cardiovasculares adversos en los pacientes con enfermedad establecida. El valor aditivo que la medición de la PCR otorga a los factores de riesgo tradicionales se refleja en novedosas calculadoras de riesgo cardiovascular y en los actuales regímenes de intervención, que ya consideran a la PCR como objetivo terapéutico. Sin embargo, las variaciones en los niveles de PCR, que dependen del sexo, la etnia, el estado hormonal y algunas peculiaridades de los ensayos de medición, deben tenerse en cuenta al decidir implementar la PCR como un biomarcador útil en el estudio y el tratamiento de la enfermedad cardiovascular aterosclerótica. Esta revisión pretende ofrecer una visión actualizada de la importancia de medir la PCR como biomarcador de riesgo cardiovascular más allá de los factores tradicionales que estiman el riesgo de enfermedad aterosclerótica.

Abstract Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

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Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

La inflamación es un factor patogénico importante para el desarrollo de la enfermedad cardiovascular aterosclerótica. Actualmente, el biomarcador utilizado con mayor frecuencia que refleja la inflamación sistémica es la proteína C reactiva (PCR), una proteína de fase aguda producida principalmente por los hepatocitos bajo la influencia de la interleucina 6, la interleucina 1 beta y el factor de necrosis tumoral. La evidencia proveniente de estudios epidemiológicos ha demostrado una fuerte asociación entre las concentraciones elevadas de PCR en suero o plasma y la incidencia de un primer evento cardiovascular (incluido infarto agudo de miocardio, accidente vascular cerebral isquémico y muerte cardíaca súbita) en la población general, así como la recurrencia de eventos cardiovasculares adversos en los pacientes con enfermedad establecida. El valor aditivo que la medición de la PCR otorga a los factores de riesgo tradicionales se refleja en novedosas calculadoras de riesgo cardiovascular y en los actuales regímenes de intervención, que ya consideran a la PCR como objetivo terapéutico. Sin embargo, las variaciones en los niveles de PCR, que dependen del sexo, la etnia, el estado hormonal y algunas peculiaridades de los ensayos de medición, deben tenerse en cuenta al decidir implementar la PCR como un biomarcador útil en el estudio y el tratamiento de la enfermedad cardiovascular aterosclerótica. Esta revisión pretende ofrecer una visión actualizada de la importancia de medir la PCR como biomarcador de riesgo cardiovascular más allá de los factores tradicionales que estiman el riesgo de enfermedad aterosclerótica.

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AIMS: PCSK9 inhibition intensively lowers low density lipoprotein cholesterol and is well tolerated in adults and paediatric patients with familial hypercholesterolaemia (FH). HAUSER-RCT showed that 24 weeks of treatment with evolocumab in paediatric patients did not affect cognitive function. This study determined the effects of 80 additional weeks of evolocumab treatment on cognitive function in paediatric patients with heterozygous FH. METHODS AND RESULTS: HAUSER-OLE was an 80-week open-label extension of HAUSER-RCT, a randomized, double-blind, 24-week trial evaluating the efficacy and safety of evolocumab in paediatric patients (ages 10-17 years) with FH. During the OLE, all patients received monthly 420 mg subcutaneous evolocumab injections. Tests of psychomotor function, attention, visual learning, and executive function were administered at baseline and Weeks 24 and 80 of the OLE. Changes over time were analysed descriptively and using analysis of covariance. Cohen's d statistic was used to evaluate the magnitude of treatment effects. Analysis of covariance results indicated no decrease in performance across visits during 80 weeks of evolocumab treatment for Groton Maze Learning, One Card Learning accuracy, Identification speed, or Detection speed (all P > 0.05). Performance on all tasks was similar for those who received placebo or evolocumab in the RCT (all P > 0.05). For all tests, the least square mean differences between patients who received placebo vs. evolocumab in the parent study were trivial (all Cohen's d magnitude < 0.2). CONCLUSION: In paediatric patients with FH, 80 weeks of open-label evolocumab treatment had no negative impact on cognitive function. REGISTRATION: ClinicalTrials.gov identifier: NCT02624869.

Some children are born with a genetic disorder that causes high cholesterol, which leads to heart disease. Children with high cholesterol can be treated with evolocumab, a medication that lowers blood cholesterol. Because cholesterol is important for development and adequate function of the brain, there is a concern that lowering cholesterol in children may affect mental ability. In this study, we tested whether treating children with evolocumab for 80 weeks affected mental ability in performing several tasks. A battery of tests that measure executive function (Groton Maze Learning Test), visual learning (One Card Learning Test), visual attention (Identification Test), and psychomotor function (Detection Test) showed no decrease in performance across visits during 80 weeks of evolocumab treatment. Performance on all tasks was similar for the children who received placebo for the first 24 weeks then received evolocumab for an additional 80 weeks (placebo/evolocumab) and those who received evolocumab for 24 weeks then received evolocumab for an additional 80 weeks (evolocumab/evolocumab).

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BACKGROUND: To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico. METHODS: CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study. RESULTS: Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1-39.6] and 29.5% [26.7-32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6-25-7], 8.4% [6.8-10.0], 5.0% [3.5-6.5] and 3.9% [2.6-5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively. CONCLUSIONS: In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit.

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Atherosclerotic cardiovascular disease (CVD) remains the leading cause of mortality worldwide. While conventional risk factors have been studied and managed, CVD continues to pose a global threat. Risk scoring systems based on these factors have been developed to predict acute coronary syndromes and guide therapeutic interventions. However, traditional risk algorithms may not fully capture the complexities of individual patients. Recent research highlights the role of inflammation, particularly chronic low-grade inflammation, in the pathogenesis of coronary artery disease (CAD). C-reactive protein (CRP) is an inflammatory molecule that has demonstrated value as a predictive marker for cardiovascular risk assessment, both independently and in conjunction with other parameters. It has been incorporated into risk assessment algorithms, enhancing risk prediction and guiding therapeutic decisions. Pharmacological interventions with anti-inflammatory properties, such as statins, glucagon-like peptide-1 agonists, and interleukin-1 inhibitors, have shown promising effects in reducing both cardiovascular risks and CRP levels. This manuscript provides a comprehensive review of CRP as a marker of systemic inflammation in CAD. By exploring the current knowledge surrounding CRP and its implications for risk prediction and therapeutic interventions, this review contributes to the advancement of personalized cardiology and the optimization of patient care.

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OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.

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Resumen: La hiperlipidemia es altamente prevalente y contribuye de forma sustancial a la enfermedad cardiovascular aterosclerótica, que es una de las principales causas de morbilidad y mortalidad en Colombia. La reducción del colesterol LDL (c-LDL) produce una disminución del riesgo de enfermedad cardiovascular aterosclerótica y de eventos cardiovasculares adversos. La terapia dirigida a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9; su sigla en inglés) ha surgido como una herramienta novedosa para el tratamiento de la hiperlipidemia. Inclisiran es un ARN pequeño de doble hebra, que actúa inhibiendo la transcripción de PCSK-9 en los hepatocitos, lo que conduce a una reducción marcada y sostenida del c-LDL. En contraste con otras terapias hipolipemiantes, como estatinas, ezetimibe y anticuerpos monoclonales (MAbs; su sigla en inglés) e inhibidores de PCSK9, inclisiran propone un régimen de dosificación infrecuente de dos o tres veces al año. Su efecto prolongado representa una ventaja frente al incumplimiento del tratamiento, que es una de las principales causas por las que no se alcanzan los objetivos de c-LDL con la terapia estándar. Esta revisión tiene como objetivo presentar y discutir los datos científicos actuales con relación a la eficacia, tolerabilidad y seguridad del inclisiran en el tratamiento de la hipercolesterolemia.

Abstract: Hyperlipidemia is a highly prevalent condition and contributes substantially to atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Colombia. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies (MAbs) PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice or three times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia.

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Introducción: La artritis reumatoide es una enfermedad autoinmune sistémica, aunque afecta fundamentalmente las articulaciones sinoviales. Más allá de las implicaciones para la calidad de vida del paciente, la presencia de la artritis reumatoide se asocia con una reducción de la esperanza de vida entre 5-10 años. La tasa de mortalidad estandarizada asociada a la artritis reumatoide es superior a la encontrada en la población no afectada; y este exceso de mortalidad se atribuye en gran medida a las enfermedades cardiovasculares, de las cuales la enfermedad vascular aterosclerótica es su principal componente. Objetivo: Determinar cómo se comportaron los factores de riesgo de enfermedad cardiovascular aterosclerótica en pacientes con diagnóstico de artritis reumatoide comparado con el grupo control. Métodos: Se realizó un estudio observacional, de tipo caso-control durante el período comprendido entre enero de 2007 y enero de 2017. Se estudiaron 110 pacientes y 220 controles. En ambos grupos se analizó la frecuencia de factores de riesgo de enfermedad cardiovascular aterosclerótica (tabaquismo, hipertensión arterial, diabetes mellitus y dislipidemia), machados por edad y sexo. Resultados: Predominaron los pacientes del sexo femenino. La mediana de edad de los pacientes fue de 41,0 años. El tabaquismo fue más frecuente en los casos (23,6 por ciento vs 11,4 por ciento, p=0,004), así como la hipertensión arterial y la diabetes mellitus. Conclusiones: En el presente estudio los factores de riesgo como el tabaquismo, la diabetes mellitus y la dislipidemia fueron más frecuentes en los pacientes son artritis reumatoide que en el grupo control(AU)

Introduction: Rheumatoid arthritis is a systemic autoimmune disease, although it mainly affects the synovial joints. Beyond the implications for the patient's quality of life, the presence of rheumatoid arthritis is associated with a reduction in life expectancy in 5-10 years. The standardized mortality rate associated with rheumatoid arthritis is higher than that found in the unaffected population; and this excess mortality is largely attributed to cardiovascular diseases, of which atherosclerotic vascular disease is the main component. Objective: To determine how the risk factors for atherosclerotic cardiovascular disease behaved in patients diagnosed with rheumatoid arthritis compared to the control group. Methods: An observational, case-control study was carried out from January 2007 to January 2017. A hundred ten (110) patients and 220 controls were studied. In both groups, the frequency of risk factors for atherosclerotic cardiovascular disease (smoking, high blood pressure, diabetes mellitus, and dyslipidemia) was analyzed, matched by age and sex. Results: Female patients predominated. The median age of the patients was 41.0 years. Smoking was more frequent variable in the cases (23.6percent vs 11.4percent, p=0.004), as well as arterial hypertension and diabetes mellitus. Conclusions: In the present study, risk factors such as smoking, diabetes mellitus and dyslipidemia were more frequent in patients with rheumatoid arthritis than in the control group(AU)

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ANTECEDENTES: Las enfermedades cardiovasculares son la principal causa mundial de mortalidad y México no es la excepción. Los datos epidemiológicos obtenidos en 1990 mostraron que los padecimientos cardiovasculares representaron el 19.8% de todas las causas de muerte en nuestro país; esta cifra se incrementó de manera significativa a un 25.5% para 2015. Diversas encuestas nacionales sugieren que más del 60% de la población adulta tiene al menos un factor de riesgo para padecer enfermedades cardiovasculares (obesidad o sobrepeso, hipertensión, tabaquismo, diabetes, dislipidemias). Por otro lado, datos de la Organización Panamericana de la Salud han relacionado el proceso de aterosclerosis como la primer causa de muerte prematura, reduciendo la expectativa de vida de manera sensible, lo que tiene una enorme repercusión social. OBJETIVO: Este documento constituye la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología en colaboración con la Sociedad Mexicana de Nutrición y Endocrinología, A.C., Asociación Nacional de Cardiólogos de México, A.C., Asociación Mexicana para la Prevención de la Aterosclerosis y sus Complicaciones, A.C., Comité Normativo Nacional de Medicina General, A.C., Colegio Nacional de Medicina Geriátrica, A.C., Colegio de Medicina Interna de México, A.C., Sociedad Mexicana de Angiología y Cirugía Vascular y Endovenosa, A.C., Instituto Mexicano de Investigaciones Nefrológicas, A.C. y la Academia Mexicana de Neurología, A.C.; con el apoyo metodológico de la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario de expertos. El objetivo de este documento es el de brindar recomendaciones basadas en evidencia para ayudar a los tomadores de decisión en el diagnóstico y tratamiento de las dislipidemias en nuestro país. MATERIAL Y MÉTODOS: Este documento cumple con estándares internacionales de calidad, como los descritos por el Instituto de Medicina de EE.UU., el Instituto de Excelencia Clínica de Gran Bretaña, la Red Colegiada para el Desarrollo de Guías de Escocia y la Red Internacional de Guías de Práctica Clínica. Se integró un grupo multidisciplinario de expertos clínicos y metodólogos con experiencia en revisiones sistemáticas de la literatura y el desarrollo de guías de práctica clínica. Se consensuó un documento de alcances, se establecieron las preguntas clínicas relevantes, se identificó de manera exhaustiva la mejor evidencia disponible evaluada críticamente en revisiones sistemáticas de la literatura y se desarrollaron las recomendaciones clínicas. Se utilizó la metodología de Panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. RESULTADOS: Se consensuaron 23 preguntas clínicas que dieron origen a sus respectivas recomendaciones clínicas. CONCLUSIONES: Esperamos que este documento contribuya a la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos y pacientes en el manejo de las dislipidemias y esto contribuya a disminuir la morbilidad y mortalidad derivada de los eventos cardiovasculares ateroscleróticos en nuestro país. BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide and Mexico is no exception. The epidemiological data obtained in 1990 showed that cardiovascular diseases represented 19.8% of all causes of death in our country. This figure increased significantly to 25.5% for 2015. Some national surveys suggest that more than 60% of the adult population has at least one risk factor for cardiovascular disease (obesity or overweight, hypertension, smoking, diabetes, dyslipidemias). On the other hand, data from the Pan American Health Organization have linked the process of atherosclerosis as the first cause of premature death, significantly reducing life expectancy, which has enormous social repercussions. OBJECTIVE: This document constitutes the Clinical Practice Guide (CPG) prepared at the initiative of the Mexican Society of Cardiology in collaboration with the Mexican Society of Nutrition and Endocrinology, AC, National Association of Cardiologists of Mexico, AC, Mexican Association for the Prevention of Atherosclerosis and its Complications, AC, National Normative Committee of General Medicine, AC, National College of Geriatric Medicine, AC, College of Internal Medicine of Mexico, AC, Mexican Society of Angiology and Vascular and Endovenous Surgery, AC, Mexican Institute of Research Nephrological, AC and the Mexican Academy of Neurology, A.C.; with the methodological support of the Ibero-American Agency for the Development and Evaluation of Health Technologies, in order to establish recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. The objective of this document is to provide evidence-based recommendations to help decision makers in the diagnosis and treatment of dyslipidemias in our country. MATERIAL AND METHODS: This document complies with international quality standards, such as those described by the Institute of Medicine of the USA, the Institute of Clinical Excellence of Great Britain, the Scottish Intercollegiate Guideline Network and the Guidelines International Network. A multidisciplinary group of clinical experts and methodologists with experience in systematic reviews of the literature and the development of clinical practice guidelines was formed. A scope document was agreed upon, relevant clinical questions were established, the best available evidence critically evaluated in systematic literature reviews was exhaustively identified, and clinical recommendations were developed. The modified Delphi Panel methodology was used to achieve an adequate level of consensus in each of the recommendations contained in this CPG. RESULTS: 23 clinical questions were agreed upon which gave rise to their respective clinical recommendations. CONCLUSIONS: We consider that this document contributes to better clinical decision-making and becomes a point of reference for clinicians and patients in the management of dyslipidemias and this contributes to reducing the morbidity and mortality derived from atherosclerotic cardiovascular events in our country.

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BACKGROUND: Hypertension, hyperglycemia, dyslipidemia, overweight, obesity, and tobacco (smoking, chewing, and vaping), together with a pro-inflammatory and procoagulant state, are the main risk factors related to atherosclerotic cardiovascular disease. OBJECTIVE AND METHODS: A group of experts from the Americas, based on their clinical expertise in cardiology, cardiovascular prevention, and cardiometabolic (CM) diseases, joined together to develop these practical recommendations for the optimal evaluation and treatment of residual CM risk factors in Latin America, using a modified Delphi methodology (details in electronic TSI) to generate a comprehensive CM risk reduction guideline, and through personalized medicine and patient-centered decision, considering the cost-benefit ratio The process was well defined to avoid conflicts of interest that could bias the discussion and recommendations. RESULTS: Residual risk reduction should consider therapeutic options adapted to specific patient needs, based on five treatment objectives: triglyceride-rich lipoproteins, inflammation, impaired glucose metabolism, high blood pressure, and prothrombotic status. Comprehensive control of all CM risk factors should be a priority to deal with this important public health problem and prevent premature deaths. The recommendations in this paper address the evidence-based treatment of CM risk and are intended for clinical application in Latin American countries.

Antecedentes: Un grupo de factores de riesgo cardiometabólicos (hipertensión, hiperglucemia, dislipidemia, sobrepeso, obesidad y tabaco (fumado, masticado, vaporizado), junto con un estado proinflamatorio y procoagulante, son los principales factores de riesgo relacionados con la enfermedad cardiovascular aterosclerótica. Objetivo y métodos: Basándose en su experiencia en cardiología, prevención cardiovascular y enfermedades cardiometabólicas, un grupo de expertos de las Américas se unió para desarrollar estas recomendaciones prácticas para la evaluación y tratamiento óptimos de los factores de riesgo cardiometabólicos residuales en América Latina, utilizando una metodología Delphi modificada con el objetivo de generar una guía integral de pautas para la reducción del riesgo cardiometabólico, mediante la medicina personalizada y la decisión centrada en el paciente teniendo en cuenta la relación costo-beneficio. El proceso fue bien definido para evitar conflictos de intereses que podrían sesgar la discusión y las recomendaciones. Resultados: La reducción del riesgo residual debe considerar opciones terapéuticas adaptadas a las necesidades específicas del paciente, basadas en 5 objetivos de tratamiento: lipoproteínas ricas en triglicéridos inflamación, metabolismo de la glucosa, presión arterial alta y estado protrombótico. El Control integral de todos los factores de riesgo cardiometabólicos debe ser una prioridad para hacer frente a este importante problema de salud pública y prevenir las muertes prematuras. Las recomendaciones de este documento abordan el tratamiento basado en evidencia del riesgo cardiometabólico y están destinadas a la aplicación clínica en los países de América Latina.

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resumen está disponible en el texto completo

Abstract Background: Cardiovascular diseases are the leading cause of mortality worldwide and Mexico is no exception. The epidemiological data obtained in 1990 showed that cardiovascular diseases represented 19.8% of all causes of death in our country. This figure increased significantly to 25.5% for 2015. Some national surveys suggest that more than 60% of the adult population has at least one risk factor for cardiovascular disease (obesity or overweight, hypertension, smoking, diabetes, dyslipidemias). On the other hand, data from the Pan American Health Organization have linked the process of atherosclerosis as the first cause of premature death, significantly reducing life expectancy, which has enormous social repercussions. Objective: This document constitutes the Clinical Practice Guide (CPG) prepared at the initiative of the Mexican Society of Cardiology in collaboration with the Mexican Society of Nutrition and Endocrinology, AC, National Association of Cardiologists of Mexico, AC, Mexican Association for the Prevention of Atherosclerosis and its Complications, AC, National Normative Committee of General Medicine, AC, National College of Geriatric Medicine, AC, College of Internal Medicine of Mexico, AC, Mexican Society of Angiology and Vascular and Endovenous Surgery, AC, Mexican Institute of Research Nephrological, AC and the Mexican Academy of Neurology, A.C.; with the methodological support of the Ibero-American Agency for the Development and Evaluation of Health Technologies, in order to establish recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. The objective of this document is to provide evidence-based recommendations to help decision makers in the diagnosis and treatment of dyslipidemias in our country. Material and methods: This document complies with international quality standards, such as those described by the Institute of Medicine of the USA, the Institute of Clinical Excellence of Great Britain, the Scottish Intercollegiate Guideline Network and the Guidelines International Network. A multidisciplinary group of clinical experts and methodologists with experience in systematic reviews of the literature and the development of clinical practice guidelines was formed. A scope document was agreed upon, relevant clinical questions were established, the best available evidence critically evaluated in systematic literature reviews was exhaustively identified, and clinical recommendations were developed. The modified Delphi Panel methodology was used to achieve an adequate level of consensus in each of the recommendations contained in this CPG. Results: 23 clinical questions were agreed upon which gave rise to their respective clinical recommendations. Conclusions: We consider that this document contributes to better clinical decision-making and becomes a point of reference for clinicians and patients in the management of dyslipidemias and this contributes to reducing the morbidity and mortality derived from atherosclerotic cardiovascular events in our country.

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Introducción: El sexo influye en la susceptibilidad de las personas de ambos géneros con relación a la mayoría de las enfermedades comunes, incluidas la diabetes mellitus y la aterosclerosis. Objetivo: Identificar si existen diferencias en la presentación de la enfermedad cardiovascular aterosclerótica entre hombres y mujeres de edad mediana con diabetes mellitus. Métodos: Se realizó un estudio descriptivo de corte transversal en 1449 pacientes con diabetes mellitus en edad mediana (40 a 59 años) que ingresaron en el Centro de Atención al Diabético de Bayamo, Granma, desde el año 2010 al 2019. Se empleó la prueba de Chi Cuadrado para comprobar la relación entre las variables cualitativas, y T de Student para comparar los valores promedio de las variables cuantitativas. Resultados: La proporción de enfermedad cardiovascular aterosclerótica en el sexo masculino fue similar a la del femenino (51,4 por ciento x 48,6 por ciento, p=0.2328). No hubo discrepancias importantes en el porcentaje de la enfermedad, entre ambos sexos, en los diferentes grupos etarios. El riesgo de enfermedad cardiovascular aterosclerótica en los hombres fue mayor que en las mujeres premenopausicas (OR=2,19, IC: 1,4-3,3 p=0,0002), pero inferior respecto a las posmenopáusicas. (OR=1.12, IC: 0.8-1.4, p=0.4129). El análisis multivariado mostró al tiempo de la diabetes >10 años y a la hipertensión arterial como riesgo de enfermedad cardiovascular aterosclerótica en ambos sexos. Asimismo, se evidenció en la edad mayor de 45 años en los hombres (OR=2.5, IC: 1.4-4.6) y la menopausia en las mujeres (OR=1.8, IC: 1.1-3.07). Conclusiones: La frecuencia de la enfermedad cardiovascular aterosclerótica en las personas de edad mediana con diabetes mellitus es similar en ambos sexos. El sexo masculino tiene mayor riesgo de enfermarse que las mujeres premenopausicas, pero menor que las posmenopáusicas. La hipertensión arterial y el tiempo de la diabetes son factores de riesgo comunes para uno y otro sexo(AU)

Introduction: Sex influences the susceptibility of people of both genders to most common diseases, including diabetes mellitus (DM) and atherosclerosis. Objective: Identify if there are differences in the presentation of atherosclerotic cardiovascular disease between middle-aged men and women with diabetes mellitus. Methods: A descriptive cross-sectional study was conducted in 1449 patients with DM in middle age (40 to 59 years) who were admitted to the Diabetic´s Care Center of Bayamo, Granma province, from 2010 to 2019. The Chi-Square test was used to check the relation between the qualitative variables, and the T Student test to compare the average values of the quantitative variables. Results: The proportion of atherosclerotic cardiovascular disease in males was similar to that of females (51.4 percent x 48.6 percent, p=0.2328). There were no major discrepancies in the percentage of atherosclerotic cardiovascular disease, between both sexes, in the different age groups. The risk of atherosclerotic cardiovascular disease in men was higher than in pre-menopausal women (OR=2.19, CI: 1.4-3.3 p=0.0002), but lower than in post-menopausal women. (OR=1.12, CI: 0.8-1.4, p=0.4129). Multivariate analysis showed diabetes >10 years and arterial hypertension as a risk of atherosclerotic cardiovascular disease in both sexes. It was also evidenced in ages over 45 years in men (OR=2.5, CI: 1.4-4.6) and menopause in women (OR=1.8, CI: 1.1-3.07). Conclusions: The frequency of atherosclerotic cardiovascular disease in middle-aged people with diabetes mellitus is similar in both sexes. Males have a higher risk of atherosclerotic cardiovascular disease than pre-menopausal women, but lower than post-menopausal women. High blood pressure and diabetes time are common risk factors for both sexes(AU)

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Resumen Se analiza la determinación de apolipoproteína B (Apo B) en la evaluación y tratamiento de la enfermedad cardiovascular aterosclerótica (ECVA) con respecto a tres aspectos: a) marcador de riesgo aterogénico; b) ventajas sobre los lípidos; c) utilidad en el laboratorio bioquímico. Apo B participa en la aterogénesis. Habitualmente las partículas lipoproteicas aterogénicas se evalúan por su contenido en colesterol pero su masa por partícula es muy variable. Sin embargo, cada partícula tiene una molécula de Apo B por lo que es un estimador de su número y marcador de riesgo. Apo B desempeña un rol causal y explica mejor que el colesterol LDL (C-LDL) la relación etiológica con la enfermedad, tiene mayor capacidad discriminante que los lípidos, agregación familiar y mejor parámetro para el manejo del tratamiento en presencia de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólico, obesidad y diabetes. Puede determinarse sin ayuno previo con trazabilidad respecto de un patrón de referencia, comparabilidad y armonía de los resultados entre los laboratorios y menor error analítico que el colesterol no-HDL. C-LDL sigue siendo el objetivo primario para la evaluación y tratamiento del riesgo aterogénico. Por consenso se han informado los valores de corte para Apo B según categorías de riesgo de ECVA y se recomendó su uso cuando sea posible determinarla. Apo B es un excelente marcador de riesgo aterogénico, presenta mayor exactitud y precisión que los lípidos y su inclusión en el manejo de casos clínicos específicos contribuye a mejorar la calidad del tratamiento.

Abstract The determination of apolipoprotein B (Apo B) in the evaluation and treatment of atherosclerotic cardiovascular disease (ACVD) is analyzed, referring to three aspects: a) marker of atherogenic risk; b) advantages over lipids; c) utility in the biochemical laboratory. Apo B participates in atherogenesis. Atherogenic lipoprotein particles are usually evaluated for their cholesterol content, but their mass per particle is highly variable. However, each particle has an Apo B molecule so it is an estimator of its number and a marker of risk. Apo B plays a causal role and explains better than LDL cholesterol (LDL-C) the etiological relationship with the disease; it has a greater discriminating capacity than lipids, family aggregation and it is a better parameter for the management of treatment in the presence of LDL-C<70 mg/dL, moderate hypertriglyceridemia, metabolic syndrome, obesity, and diabetes. It can be determined without prior fasting with traceability to a reference standard, comparability and harmony of results between laboratories and lower analytical error than non-HDL cholesterol. LDL-C remains the primary endpoint for the evaluation and treatment of atherogenic risk. By consensus, cut-off values for Apo B have been reported according to ACVD risk categories and its use was recommended when it is possible to determine it. Apo B is an excellent marker of atherogenic risk, it has greater accuracy and precision than lipids and its inclusion in the management of specific clinical cases contributes to improving the quality of treatment.

Resumo A determinação da apolipoproteína B (Apo B) na avaliação e tratamento da doença cardiovascular aterosclerótica (DCVA) é analisada, referindo-se a três aspectos: a) marcador de risco aterogênico; b) vantagens sobre os lipídios; c) utilidade no laboratório bioquímico. Apo B participa da aterogênese. As partículas de lipoproteína aterogênica são geralmente avaliadas quanto ao seu conteúdo de colesterol, mas sua massa por partícula é altamente variável. No entanto, cada partícula possui uma molécula de Apo B, por isso é um estimador de seu número e um marcador de risco. A Apo B tem papel causal e explica melhor que o colesterol LDL (C-LDL) a relação etiológica com a doença, tem maior capacidade discriminante que os lipídios, agregação familiar e melhor parâmetro para o manejo do tratamento na presença de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólica, obesidade e diabetes. Pode ser determinado sem jejum prévio com rastreabilidade a respeito de um padrão de referência, comparabilidade e harmonia de resultados entre laboratórios e menor erro analítico do que o colesterol não-HDL. O C-LDL continua sendo o objetivo primário para a avaliação e tratamento do risco aterogênico. Por consenso, os valores de corte da Apo B foram reportados de acordo com as categorias de risco de DCVA e seu uso foi recomendado quando possível. A Apo B é um excelente marcador de risco aterogênico, possui maior acurácia e precisão que os lipídeos e sua inclusão no manejo de casos clínicos específicos contribui para a melhoria da qualidade do tratamento.

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In this eight-year retrospective study, we evaluated the associations between climatic variations and the biological rhythms in plasma lipids and lipoproteins in a large population of Campinas, São Paulo state, Brazil, as well as temporal changes of outcomes of cardiovascular hospitalizations. Climatic variables were obtained at the Center for Meteorological and Climatic Research Applied to Agriculture (University of Campinas - Unicamp, Brazil). The plasma lipid databases surveyed were from 27,543 individuals who had their lipid profiles assessed at the state university referral hospital in Campinas (Unicamp). The frequency of hospitalizations was obtained from the Brazilian Public Health database (DATASUS). Temporal statistical analyses were performed using the methods Cosinor or Friedman (ARIMA) and the temporal series were compared by cross-correlation functions. In normolipidemic cases (n=11,892), significantly different rhythmicity was observed in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (C) both higher in winter and lower in summer. Dyslipidemia (n=15,651) increased the number and amplitude of lipid rhythms: LDL-C and HDL-C were higher in winter and lower in summer, and the opposite occurred with triglycerides. The number of hospitalizations showed maximum and minimum frequencies in winter and in summer, respectively. A coincident rhythmicity was observed of lower temperature and humidity rates with higher plasma LDL-C, and their temporal series were inversely cross-correlated. This study shows for the first time that variations of temperature, humidity, and daylight length were strongly associated with LDL-C and HDL-C seasonality, but moderately to lowly associated with rhythmicity of atherosclerotic outcomes. It also indicates unfavorable cardiovascular-related changes during wintertime.

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Resumen Introducción: Los pacientes con enfermedad aterosclerótica establecida requieren tratamiento con estatinas para reducir la probabilidad de nuevos eventos. Objetivo: Identificar el porcentaje de pacientes con enfermedad coronaria aterosclerótica establecida que logran niveles de cLDL (colesterol LDL) inferiores a 70mg/dl y describir su distribución en tres grupos terapéuticos: estatinas, otros hipolipemiantes y sin tratamiento. Métodos: Estudio observacional descriptivo de corte transversal, en el que se seleccionaron pacientes de tres hospitales de alta complejidad, mayores de 18 años, con enfermedad aterosclerótica diagnosticada a partir del año 2017. El registro del perfil lipídico corresponde al realizado al menos tres meses después del diagnóstico. Resultados: Se incluyeron en total 746 pacientes con enfermedad coronaria aterosclerótica, con un promedio de edad de 65,3±10,9 años y predominio del sexo masculino (75,5%). Del total de los pacientes evaluados se prescribieron un 97,8% de terapia con al menos una estatina, 0,7% de otros hipolipemiantes y 1,5% no presentaron tratamiento. Los pacientes con niveles de cLDL inferior a 70mg/dl corresponden al 56%. Conclusiones: La extensa divulgación de guías de práctica clínica para dislipidemias en adultos en Colombia, y la incorporación de estatinas de alta intensidad, demuestran una mejoría en la proporción del cumplimiento en metas de cLDL para pacientes con enfermedad aterosclerótica establecida. Sin embargo, una alta proporción aún persiste fuera de metas, lo cual constituye una oportunidad de optimización del uso de terapias disponibles y recientemente desarrolladas.

Abstract Introduction: Patients with established atherosclerotic disease require treatment with statins in order to reduce the probability of new events. Objective: To identify the percentage of patients with established atherosclerotic coronary disease that achieve cLDL (LDL - cholesterol) levels less than 70mg/dL, and to describe its distribution in three treatment groups: statins, other lipid lowering drugs, and without treatment. Methods: A cross-sectional, descriptive observational study was conducted on patients diagnosed with atherosclerotic disease from 2017 and over 18-years-old from 3 tertiary hospitals. A record was made of the lipid profile that was performed at least three months after the diagnosis. Results: A total of 746 patients with atherosclerotic coronary disease were included. The mean age was 65.3±10.9 years and the majority (75.5%) were males. Of the total number of patients evaluated, 97.8% were prescribed a therapy with at least one statin, 0.7% with other lipid-lowering drugs, and 1.5% had no treatment. Just over half (56%) of the patients had cLDL levels of less than 70mg/dL. Conclusions: The widespread use of clinical practice guidelines for dyslipidaemias in adults in Colombia, and the incorporation of high-intensity statins, has led to an improvement in the proportion of patients with established atherosclerotic disease achieving cLDL targets. However, a high percentage still does not reach the targets, which suggests a need for an improving of the use of available and recently developed therapies.

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Diversos estudios evidencian la asociación entre los niveles elevados del colesterol de LDL (cLDL) y el riesgo de desarrollar enfermedad cardiovascular aterosclerótica. Con el objetivo de comparar los valores de cLDL obtenidos mediante la medición directa y los valores estimados por las ecuaciones de Friedewald tradicional, modificada y de regresión, se valoró el cLDL de 4.621 pacientes mediante el ensayo directo en el autoanalizador ADVIA 1800. Dichos resultados se agruparon en los estados de normolipemia, hipercolesterolemia, hiperlipemia mixta e hipertrigliceridemia y se establecieron diferencias de estimación con las mencionadas fórmulas en el total de la muestra y en los niveles de decisión clínica para el cLDL. Las tres fórmulas presentaron correlación significativa con el método directo en la totalidad de la muestra; sin embargo, cuando los niveles de triglicéridos de las muestras superaron los 200 mg/dL, la diferencia entre la fórmula de Friedewald y el método directo resultó -11,94%, y llegó a -19,13% para el nivel de triglicéridos mayor de 400 mg/dL. Por otro lado, las ecuaciones de Friedewald modificada y de regresión se vieron afectadas en menor cuantía por el nivel de triglicéridos. Las fórmulas de regresión y de Friedewald modificada se constituyen como alternativas razonables para estimar el cLDL y presentan buena concordancia con el método directo, incluso en niveles altos de colesterol y triglicéridos.

Several studies show the association between high LDL cholesterol (LDLc) levels and the risk of developing atherosclerotic cardiovascular disease. In order to compare the LDLc values obtained by direct measurement and the values estimated by the traditional, modified and regression Friedewald equations, the LDLc of 4,621 patients was assessed by means of the direct test in the ADVIA 1800 autoanalyzer.These results were grouped into the states of normolipemia, hypercholesterolemia, mixed hyperlipemia and hypertriglyceridemia, establishing differences in estimation with the aforementioned formulas in the total sample and in clinical decision levels for LDLc. The three formulas showed a significant correlation with the direct method in the entire sample; however, when the triglyceride levels of the samples exceeded 200 mg/dL, the difference between Friedewald's formula and the direct method was -11.94% reaching -19,13% for the triglyceride level greater than 400 mg/dL, while the modified Friedewald and regression equations were affected to a lesser extent by the triglyceride level. Regression and modified Friedewald formulas are constituted as reasonable alternatives to estimate LDLc and have good agreement with the direct method, even at high cholesterol and triglyceride levels.

Varios estudos evidenciam a associacao entre niveis elevados do colesterol LDL (cLDL) e o risco de desenvolver doenca cardiovascular aterosclerotica. Visando comparar os valores de cLDL obtidos atraves da medicao direta e os valores estimados pelas equacoes de Friedewald tradicional, modificada e de regressao, o cLDL de 4.621 pacientes foi avaliado por meio do teste direto no analisador automatico ADVIA 1800. Tais resultados foram agrupados nos estados de normolipemia, hipercolesterolemia, hiperlipemia mista e hipertrigliceridemia, estabelecendo-se diferencas na estimativa com as formulas mencionadas no total da amostra e nos niveis de decisao clinica para cLDL. As tres formulas apresentaram correlacao significativa com o metodo direto em toda a amostra, no entanto, quando os niveis de triglicerideos das amostras excederam 200 mg/dL, a diferenca entre a formula de Friedewald e o metodo direto foi de -11,94% atingindo -19,13% para o nivel de triglicerideos superior a 400 mg/dL. Por outra parte, as equacoes de Friedewald modificada e de regressao foram afetadas em menor grau pelo nivel de triglicerideos. As formulas de regressao e de Friedewald modificada se constituem como alternativas razoaveis para estimar o cLDL, e apresentam boa concordancia com o metodo direto, mesmo em niveis elevados de colesterol e triglicerideos.

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BACKGROUND: Implementing evidence-based management of dyslipidaemia is a challenge worldwide. OBJECTIVES: To understand physician beliefs and behaviour and identify uncertainties in dyslipidaemia management across four world regions. METHODS: Web-based survey of 1758 physicians in Japan, Germany, Colombia and the Philippines who were selected randomly from existing databases. Key inclusion criteria were 1) for cardiologists and diabetes/endocrinology specialists: ≥50 dyslipidaemia patients examined in the last month; 2) for specialists in neurology/neurosurgery/stroke medicine: ≥50 dyslipidaemia patients and ≥ 20 patients with a history of ischaemic stroke examined in the last month; and 3) for specialists in nephrology and general medicine: based at centres with ≥20 beds and ≥ 50 dyslipidaemia patients examined in the last month. The self-report survey covered dyslipidaemia management, target low-density lipoprotein cholesterol (LDL-C) levels in different patient groups, and statin safety. All physicians gave voluntary consent and all data were anonymised. Analysis was solely descriptive. RESULTS: The survey highlighted key areas of uncertainty in dyslipidaemia management in the four countries. These related to LDL-C targets in different patient groups, the safety of low LDL-C levels, the safety of statins, especially for effects on cognitive, renal and hepatic function and for haemorrhagic stroke risk, and lipid management strategies in patients with chronic kidney disease, including those with concomitant hypertriglyceridaemia. CONCLUSIONS: This survey of physicians in Japan, Germany, Colombia and the Philippines has identified key gaps in knowledge about dyslipidaemia management. These relate to the safety of low LDL-C levels, the safety of statins, and lipid management of chronic kidney disease. The findings from this survey highlight the need for further education to improve the implementation of guideline recommendations for dyslipidaemia management.

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La importancia de la nutrición en modificar el riesgo de enfermedad cardiovascular aterosclerótica (ECVA) se ha enfatizado repetidas veces. Históricamente, el papel de los componentes dietarios ha sido el foco predominante; sin embargo, los alimentos, típicamente, se consumen en combinación más que aisladamente. En los últimos años, se ha puesto una mayor atención a los patrones dietarios y su relación con eventos clínicos del tipo de la ECVA, diabetes mellitus tipo 2 y obesidad; paradójicamente, existe una brecha en la educación nutricional en las escuelas de medicina de todo el mundo. Por lo general, una dieta no saludable está asociada con alteraciones cardiometabólicas, una condición clínica que, gradualmente, puede empeorar y conducir a diversos factores comunes de riesgo de enfermedades crónicas, a mayor morbilidad y mortalidad y menoscabo en la calidad de vida. El público en general debe satisfacer la cantidad de calorías requeridas con una variedad de alimentos densos en nutrientes que abarquen todos los grupos de alimentos para mantener la salud a largo plazo. El estilo de patrones saludables de comer varía individualmente y frecuentemente refleja las preferencias culturales y personales. Una alimentación no saludable puede causar una elevación de la producción posprandial de insulina e hipersecreción crónica de insulina e hiperinsulinemia, lo cual promueve la acumulación de grasa, previene la lipólisis y causa incremento en el riesgo de desarrollar ECVA, obesidad y diabetes tipo(AU)

The importance of nutrition in modifying the risk of atherosclerotic cardiovascular disease (ACVD) has been repeatedly emphasized. Historically, the role of dietary components has been the predominant focus; however, foods are typically consumed in combinations rather than individually. Over the last few years, increasing attention has been given to dietary patterns and their relationship to clinical events such as ACVD, type 2 diabetes and obesity; paradoxically, there is a gap in nutrition education in medical school around the globe. An unhealthy diet is usually associated with cardiometabolic alterations, a clinical situation that can progressively worse, potentially leading to various common risk factors, increased morbidity and mortality, and reduced quality of life. People should aim to fulfill their recommended calorie intake with a variety of nutrient-dense foods that span all food groups to boost long-term health. Healthy eating styles may vary from individual to individual and frequently reflect cultural and personal preferences. An unhealthy diet may cause a high postprandial insulin production and chronic insulin hypersecretion and hyperinsulinemia, which promote fat storage, prevent lipolysis and cause increased the risk for developing ACVD, obesity and type 2 diabetes

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Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease. FH is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (APOB) and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9). However, the phenotype may be encountered in individuals not carrying the latter monogenic defects, in approximately 20% of these effects of polygenes predominate, and in many individuals no molecular defects are encountered at all. These so-called FH phenocopy individuals have an elevated atherosclerotic cardiovascular disease risk in comparison with normolipidemic individuals but this risk is lower than in those with monogenic disease. Individuals with FH are exposed to elevated LDL-C levels since birth and this explains the high cardiovascular, mainly coronary heart disease, burden of these subjects. However, recent studies show that this risk is heterogenous and depends not only on high LDL-C levels but also on presence of previous cardiovascular disease, a monogenic cause, male sex, smoking, hypertension, diabetes, low HDL-cholesterol, obesity and elevated lipoprotein(a). This heterogeneity in risk can be captured by risk equations like one from the SAFEHEART cohort and by detection of subclinical coronary atherosclerosis. High dose high potency statins are the main stain for LDL-C lowering in FH, however, in most situations these medications are not powered enough to reduce cholesterol to adequate levels. Ezetimibe and PCSK9 inhibitors should also be used in order to better treat LDL-C in FH patients.

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