Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.

Statin-associated muscle symptoms: position paper from the Luso-Latin American Consortium.

In the last two decades, statin therapy has proved to be the most potent isolated therapy for attenuation of cardiovascular risk. Its frequent use has been seen as one of the most important elements for the reduction of cardiovascular mortality in developed countries. However, the recurrent incidence of muscle symptoms in statin users raised the possibility of causal association, leading to a disease entity known as statin associated muscle symptoms (SAMS). Mechanistic studies and clinical trials, specifically designed for the study of SAMS have allowed a deeper understanding of the natural history and accurate incidence. This set of information becomes essential to avoid an unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents overdiagnosis and an inadequate suspension of one of the most powerful prevention strategies of our times. In this context, the Luso-Latin American Consortium gathered all available information on the subject and presents them in detail in this document as the basis for the identification and management of SAMS.

Efecto de la inhibición de la proteína símil angiopoyetina tipo 3 (ANGPTL3): utilidad para el tratamiento de las dislipemias graves / Angiopoietin-like type 3 (angptl) inhibition: its role in the treatment of severe dyslipidemia

Las variantes de ANGPTL3 con pérdida de función están asociadas con efectos beneficiosos sobre el metabolismo lipídico y de carbohidratos y con riesgo reducido de enfermedad coronaria. Los cambios beneficiosos en los parámetros lipídicos que se obtienen con la inhibición de ANGPTL3 junto con la reducción en aterosclerosis que se observa en modelos animales y en estudios epidemiológicos de genética humana hacen de ANGPTL3 un nuevo objetivo terapéutico para prevenir las enfermedades cardiovasculares. Dos estrategias novedosas han surgido para inhibir esta proteína: un anticuerpo monoclonal y un oligonucleótido antisentido, con capacidad para reducir tanto el colesterol como los triglicéridos plasmáticos en forma notoria. Aunque el horizonte es promisorio, todavía no sabemos si los efectos de una variante presente desde el comienzo de la vida serán reproducidos por la inhibición de esta proteína que se realiza más tarde en la vida a través de una intervención farmacológica. (AU)

Loss-of-function ANGPTL3 variants are associated with beneficial effects on carbohydrate and lipid metabolism, and reduced risk of coronary heart disease. The beneficial changes in lipid parameters obtained by ANGPTL3 inhibition together with atheroprotection observed in animal models and in epi-demiological studies of human genetics make ANGPTL3 a new therapeutic target to prevent cardiovascular diseases. Two novel strategies have emerged to inhibit this protein: a monoclonal antibody and an antisense oligonucleotide, with the ability to significantly lower plasma cholesterol and triglycerides. Although the horizon is promising, we still do not know if the effects of a variant present from the beginning of life will be reproduced by the inhibition of this protein that takes place later in life through a pharmacological intervention. (AU)

Endothelial and leukocyte adhesion molecules in primary hypertriglyceridemia.

Hypertriglyceridemia is known to be associated to functional impairment of the endothelium and, consequently, to higher risk of atherosclerosis. Nevertheless, some crucial steps in the development of the atherosclerotic plaque are still unknown in primary hypertriglyceridemia. The aim of the present study was to explore the expression of soluble and leukocyte-associated cell adhesion molecules in a group of patients with primary hypertriglyceridemia, both including (n=50) and excluding (n=24) subjects with metabolic syndrome, in comparison with control normotriglyceridemic individuals (n=30). Lipid profile, CETP activity, HDL and VLDL chemical composition were evaluated. Soluble (VCAM-1, ICAM-1 and E-selectin) and leukocyte cell adhesion molecules (CD18, CD49d and CD54) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. Patients with primary hypertriglyceridemia as compared with control subjects showed significantly higher VCAM-1 (15.6+/-4.5 ng/ml versus 13.9+/-3.8 ng/ml, respectively; p<0.05) and ICAM-1 (16.9+/-3.1 ng/ml versus 15.2+/-3.2 ng/ml, respectively; p<0.05). Regarding leukocyte cell adhesion molecules, significant increases were also detected in monocyte CD18 (398+/-180 versus 332+/-136 arbitrary units, respectively; p<0.05) and CD54 (49+/-14 versus 42+/-12 arbitrary units, respectively; p<0.05), and lymphocyte CD18 (122+/-53 versus 101+/-33 arbitrary units, respectively; p<0.05). ICAM-1 plasma levels, as well as monocyte CD18 and CD54, and lymphocyte CD18 persisted elevated even if patients with metabolic syndrome were discarded among those with hypertriglyceridemia. The increase in circulating and leukocyte cell adhesion molecules in primary hypertriglyceridemic patients would highlight the inflammatory process which is a key event in atherogenesis.

Statin-associated muscle symptoms: position paper from the Luso-Latin American Consortium

In the last two decades, statin therapy has proved to be the most potent isolated therapy for attenuation of cardiovascular risk. Its frequent use has been seen as one of the most important elements for the reduction of cardiovascular mortality in developed countries. However, the recurrent incidence of muscle symptoms in statin users raised the possibility of causal association, leading to a disease entity known as statin associated muscle symptoms (SAMS). Mechanistic studies and clinical trials, specifically designed for the study of SAMS have allowed a deeper understanding of the natural history and accurate incidence. This set of information becomes essential to avoid an unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents overdiagnosis and an inadequate suspension of one of the most powerful prevention strategies of our times. In this context, the Luso-Latin American Consortium gathered all available information on the subject and presents them in detail in this document as the basis for the identification and management of SAMS...

Aterosclerosis subclínica y estimación de riesgo coronario: comparación de tablas de riesgo / Subclinical atherosclerosis and coronary risk assessment: comparing risk tables

Para guiar el tratamiento preventivo se utilizan distintas tablas de estimación de riesgo coronario. Por otro lado, las alteraciones de la pared arterial son una manifestación de aterosclerosis subclínica y su detección mediante ecografía puede emplearse para predecir eventos coronarios. Objetivo: Comparar la prevalencia de aterosclerosis subclínica evaluada mediante ecografía carótidofemoral entre grupos de bajo riesgo definidos por diferentes tablas. Material y métodos: Se estudiaron 151 pacientes dislipidémicos con edad de 53 ± 12 años (rango: 20-82 años; 45 por ciento varones), índice de masa corporal: 26 ± 3 kg/m2, 42 por ciento hipertensos, 17 por ciento tabaquistas y3 por ciento diabéticos a los que se les realizaron ecografías carótido-femorales y que calificaron paraevaluación de riesgo. Se calculó el riesgo individual mediante diferentes tablas de estimación de riesgo y se incluyeron los individuos con riesgo coronario estimado menor del 10 por ciento a diez años. Se excluyeron del análisis los pacientes con riesgo moderado y alto. Se definió aterosclerosis subclínica a la presencia de placas ateroscleróticas en la ecografía arterial. Secomparó la prevalencia de aterosclerosis subclínica entre los grupos de bajo riesgo. Resultados: Uno de cada dos pacientes considerados de bajo riesgo presentó aterosclerosis subclínica, independientemente de la tabla utilizada. No hubo diferencias significativas en la prevalencia de aterosclerosis subclínica entre subgrupos. El 73 por ciento de los pacientes fueron categorizados de bajo riesgo por ATP III y el 78 por ciento por AHA/ACC, en comparación con el 45 por ciento calculado por Europea II (p < 0,001). Conclusiones: La ecografía carótido-femoral complementa la evaluación realizada mediante tablas de riesgo en la toma de decisiones terapéuticas en prevención primaria.

Aterosclerosis subclínica y estimación de riesgo coronario: comparación de tablas de riesgo / Subclinical atherosclerosis and coronary risk assessment: comparing risk tables

Para guiar el tratamiento preventivo se utilizan distintas tablas de estimación de riesgo coronario. Por otro lado, las alteraciones de la pared arterial son una manifestación de aterosclerosis subclínica y su detección mediante ecografía puede emplearse para predecir eventos coronarios. Objetivo: Comparar la prevalencia de aterosclerosis subclínica evaluada mediante ecografía carótidofemoral entre grupos de bajo riesgo definidos por diferentes tablas. Material y métodos: Se estudiaron 151 pacientes dislipidémicos con edad de 53 ± 12 años (rango: 20-82 años; 45 por ciento varones), índice de masa corporal: 26 ± 3 kg/m2, 42 por ciento hipertensos, 17 por ciento tabaquistas y3 por ciento diabéticos a los que se les realizaron ecografías carótido-femorales y que calificaron paraevaluación de riesgo. Se calculó el riesgo individual mediante diferentes tablas de estimación de riesgo y se incluyeron los individuos con riesgo coronario estimado menor del 10 por ciento a diez años. Se excluyeron del análisis los pacientes con riesgo moderado y alto. Se definió aterosclerosis subclínica a la presencia de placas ateroscleróticas en la ecografía arterial. Secomparó la prevalencia de aterosclerosis subclínica entre los grupos de bajo riesgo. Resultados: Uno de cada dos pacientes considerados de bajo riesgo presentó aterosclerosis subclínica, independientemente de la tabla utilizada. No hubo diferencias significativas en la prevalencia de aterosclerosis subclínica entre subgrupos. El 73 por ciento de los pacientes fueron categorizados de bajo riesgo por ATP III y el 78 por ciento por AHA/ACC, en comparación con el 45 por ciento calculado por Europea II (p < 0,001). Conclusiones: La ecografía carótido-femoral complementa la evaluación realizada mediante tablas de riesgo en la toma de decisiones terapéuticas en prevención primaria.(AU)

Oportunidades y desafíos en el manejo de las dislipidemias / Opportunities and challenges in the management of dislipidemia

Mucho se ha avanzado en el adecuado enfoque de las dislipidemias. Los tratamientos actuales muestran su eficacia y las novedosas herramientas que surgen permitirán practicar una medicina individualizada. La prevención desde la infancia es nuestra mayor oportunidad.

Oportunidades y desafíos en el manejo de las dislipidemias / Opportunities and challenges in the management of dislipidemia

Mucho se ha avanzado en el adecuado enfoque de las dislipidemias. Los tratamientos actuales muestran su eficacia y las novedosas herramientas que surgen permitirán practicar una medicina individualizada. La prevención desde la infancia es nuestra mayor oportunidad.(AU)

Determinación no invasiva de aterosclerosis subclínica y estratificación del riesgo cardiovascular / Non invasive assessment of subclinical atherosclerosis and stratification of cardiovascular risk

At present, cardiovascular diseases are the most frequent cause of morbidity and mortality in the world. Atherosclerosis has an important roll in the pathophysiology of cardiovascular diseases, mainly on the ischemic cardiopathy...The incorporation of ultrasonic screening for non invasive detection of subclinical atherosclerosis would allow the identification of a higher numbe of patients at high risk for coronary event and recommended for primary prevention