Challenges in familial chylomicronemia syndrome diagnosis and management across Latin American countries: An expert panel discussion.

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by extremely high triglyceride levels due to impaired clearance of chylomicrons from plasma. This paper is the result of a panel discussion with Latin American specialists who raised the main issues on diagnosis and management of FCS in their countries. Overall FCS is diagnosed late on the course of the disease, is characterized by heterogeneity on the occurrence of pancreatitis, and remains a long time in care of different specialists until reaching a lipidologist. Pancreatitis and secondary diabetes are frequently seen, often due to late diagnosis and inadequate care. Molecular diagnosis is unusual; however, loss of function variants on the lipoprotein lipase gene are apparently the most frequent etiology. A founder effect of the glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gene has been described in the northeast of Brazil. Low awareness of the disease amongst health professionals contributes to inadequate care and an inadequate patient journey.

Diagnosis and Management of Statin Intolerance.

Statins are the main treatment for hypercholesterolemia and the cornerstone of atherosclerotic cardiovascular disease prevention. Many patients taking statins report muscle-related symptoms, one of the most important causes of statin treatment discontinuation, which is associated with an increased risk of cardiovascular events. Therefore, it is important to identify patients who are truly statin intolerant to avoid unnecessary discontinuation of this beneficial treatment. Some studies indicate that not all muscle complaints are caused by statins, and most patients can tolerate a statin upon re-challenge, down-titration of dose, or switching to another statin. In this paper, we review the definitions of statin intolerance and approaches to reducing cardiovascular risk among individuals reporting statin-associated muscle symptoms.

[Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia]. / Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2 / Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

INTRODUCTION: The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. AIMS: To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. METHODS: Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. RESULTS: A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). CONCLUSION: In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

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.

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...

Diabetes and Quality of Life: Initial Approach to Depression, Physical Activity, and Sexual Dysfunction.

The different aspects that contribute to quality of life in patients with diabetes mellitus, such as mood, are of great importance for the treatment of this disease. These aspects not only influence the well-being of patients but also influence treatment adherence, therefore affecting the course of the disease. A panel of experts from Argentina, Chile, and Uruguay performed a review of the main aspects affecting quality of life in patients with diabetes: physical activity, mood disorders, and sexual activity. The consensus of the panel was that physical activity is important in the treatment of patients with diabetes because it reduces morbidity, mortality, and disease complications, and it should be performed on a regular basis, bearing in mind the patient's characteristics. Increased physical activity is associated with better glycemic control, and in individuals with glucose intolerance, it delays progression toward diabetes. In patients with diabetes, there is a high prevalence of depression, which can influence treatment adherence. Therefore, early detection of depression is essential to improve the course of diabetes. Regarding sexual activity, erectile dysfunction may be a significant sign in the case of suspected diabetes and the early diagnosis of vasculopathy in patients with diabetes. In conclusion, greater emphasis should be placed on improving patient knowledge, early detection, and multidisciplinary approaches to deal with the aspects of diabetes that affect patients' quality of life.

Estimación del riesgo cardiovascular y detección de ateromatosis carotídea subclínica en mujeres posmenopáusicas de mediana edad / Estimation of Cardiovascular Risk and Detection of Subclinical Carotid Atheromatosis in Middle-aged Postmenopausal Women

Introducción La incidencia de enfermedad cardiovascular en la mujer aumenta luego de la menopausia.Los puntajes de riesgo tradicionales subestiman el riesgo en la mujer posmenopáusica. El diagnóstico de placa aterosclerótica carotídea (PAC) podría mejorar la estratificación del riesgo. Objetivos 1) Estimar el riesgo cardiovascular en mujeres posmenopáusicas de mediana edad en prevención primaria. 2) Conocer la prevalencia de PAC. 3) Calcular la precisión de los puntajes de riesgo para detectar PAC. Material y métodos Se calcularon el puntaje de Framingham a 10 años (PF10) y el puntaje recomendado por la Organización Mundial de la Salud (POMS), evaluando la concordancia entre ellos. Se determinó la prevalencia de PAC mediante ultrasonido. Se realizó un análisis ROC. Resultados Se incluyeron 334 mujeres (edad 57 ± 5 años). El 96% y el 91% de la población se clasificó como de "riesgo bajo" según el PF10 y el POMS, respectivamente. La concordancia entre los dos puntajes fue regular (kappa 0,31). La prevalencia de PAC fue del 29%. Se observó una correspondencia entre el riesgo estimado por los puntajes y la prevalencia de PAC. Las mujeres con PAC presentaron una prevalencia mayor de hipertensión arterial y tabaquismo, mostrando más frecuentemente un patrón "metabólico" que las mujeres sin PAC. El área bajo la curva del PF10 para detectar PAC fue de 0,79 (IC 95% 0,73-0,84), siendo el punto de corte óptimo = 3%. Conclusiones En esta población clasificada en su mayoría como de riesgo bajo, la prevalencia de PAC fue considerable. Ante un PF10 = 3%, la solicitud de una ecografía carotídea podría optimizar la estratificación del riesgo cardiovascular.(AU)

Background Cardiovascular disease in women increases after menopause. Traditional risk scores underestimate the risk in postmeno-pausal women. The diagnosis of carotid atherosclerotic plaque (CAP) could improve risk stratification. Objectives The aim of the study was: 1) To estimate cardiovascular risk in middle-aged postmenopausal women in primary preven-tion. 2) To find CAP prevalence. 3) To assess the precision of risk scores used to detect CAP. Methods The level of agreement between the 10-year Framingham risk score (10-FRS) and the score recommended by the World Health Organization (WHOS) was assessed. Ultrasound was used to determine CAP occurrence. A ROC analysis was performed. Results The study included a total of 334 women with mean age 57 ± 5 years. According to 10-FRS and WHOS, 96% and 91% of the population were respectively classified as "low risk". An adequate level of agreement between both scores was found (kappa 0.31). CAP occurred in 29% of cases. Score estimated risk correlated with CAP prevalence. Women with CAP presented higher incidence of hypertension and smoking, evidencing a more frequent "metabolic" pattern than women without CAP. The area under the curve of 10-FRS to detect CAP was 0.79 (95% CI 0.73-0.84), with an optimal cut-off point = 3%. Conclusions In this population, mostly classified as low risk, there was considerable CAP prevalence. A carotid ultrasound might help to stratify cardiovascular risk when 10-FRS is = 3%.(AU)

Estimación del riesgo cardiovascular y detección de ateromatosis carotídea subclínica en mujeres posmenopáusicas de mediana edad / Estimation of Cardiovascular Risk and Detection of Subclinical Carotid Atheromatosis in Middle-aged Postmenopausal Women

Introducción La incidencia de enfermedad cardiovascular en la mujer aumenta luego de la menopausia.Los puntajes de riesgo tradicionales subestiman el riesgo en la mujer posmenopáusica. El diagnóstico de placa aterosclerótica carotídea (PAC) podría mejorar la estratificación del riesgo. Objetivos 1) Estimar el riesgo cardiovascular en mujeres posmenopáusicas de mediana edad en prevención primaria. 2) Conocer la prevalencia de PAC. 3) Calcular la precisión de los puntajes de riesgo para detectar PAC. Material y métodos Se calcularon el puntaje de Framingham a 10 años (PF10) y el puntaje recomendado por la Organización Mundial de la Salud (POMS), evaluando la concordancia entre ellos. Se determinó la prevalencia de PAC mediante ultrasonido. Se realizó un análisis ROC. Resultados Se incluyeron 334 mujeres (edad 57 ± 5 años). El 96% y el 91% de la población se clasificó como de "riesgo bajo" según el PF10 y el POMS, respectivamente. La concordancia entre los dos puntajes fue regular (kappa 0,31). La prevalencia de PAC fue del 29%. Se observó una correspondencia entre el riesgo estimado por los puntajes y la prevalencia de PAC. Las mujeres con PAC presentaron una prevalencia mayor de hipertensión arterial y tabaquismo, mostrando más frecuentemente un patrón "metabólico" que las mujeres sin PAC. El área bajo la curva del PF10 para detectar PAC fue de 0,79 (IC 95% 0,73-0,84), siendo el punto de corte óptimo = 3%. Conclusiones En esta población clasificada en su mayoría como de riesgo bajo, la prevalencia de PAC fue considerable. Ante un PF10 = 3%, la solicitud de una ecografía carotídea podría optimizar la estratificación del riesgo cardiovascular.

Background Cardiovascular disease in women increases after menopause. Traditional risk scores underestimate the risk in postmeno-pausal women. The diagnosis of carotid atherosclerotic plaque (CAP) could improve risk stratification. Objectives The aim of the study was: 1) To estimate cardiovascular risk in middle-aged postmenopausal women in primary preven-tion. 2) To find CAP prevalence. 3) To assess the precision of risk scores used to detect CAP. Methods The level of agreement between the 10-year Framingham risk score (10-FRS) and the score recommended by the World Health Organization (WHOS) was assessed. Ultrasound was used to determine CAP occurrence. A ROC analysis was performed. Results The study included a total of 334 women with mean age 57 ± 5 years. According to 10-FRS and WHOS, 96% and 91% of the population were respectively classified as "low risk". An adequate level of agreement between both scores was found (kappa 0.31). CAP occurred in 29% of cases. Score estimated risk correlated with CAP prevalence. Women with CAP presented higher incidence of hypertension and smoking, evidencing a more frequent "metabolic" pattern than women without CAP. The area under the curve of 10-FRS to detect CAP was 0.79 (95% CI 0.73-0.84), with an optimal cut-off point = 3%. Conclusions In this population, mostly classified as low risk, there was considerable CAP prevalence. A carotid ultrasound might help to stratify cardiovascular risk when 10-FRS is = 3%.