Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.

BACKGROUND: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. METHODS: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants. RESULTS: LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. CONCLUSION: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p.V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.

A Latin American perspective on the new ACC/AHA clinical guidelines for managing atherosclerotic cardiovascular disease.

Atherosclerotic heart disease and stroke are leading causes of disability and death worldwide, affecting not only developed countries, but also low- and middle-income regions. Different strategies for handling dyslipidemia as a critical pathogenic risk factor for atherosclerosis have been proposed. However, these recommendations are not applied at all in many countries or even in whole regions of the world. Recently, new US guidelines on risk assessment, lifestyle changes, and high blood cholesterol level treatment to manage atherosclerotic disease were released. In this article, we analyze these new guidelines and discuss their potential applications in preventive cardiovascular medicine in Latin America.

[Association between diabetes mellitus and cardiovascular disease in Chilean adults: analysis of the National Health Survey 2009-2010]. / Asociación entre diabetes mellitus y patología cardiovascular en la población adulta de Chile: estudio de la Encuesta Nacional de Salud 2009-2010.

BACKGROUND: Diabetes mellitus (DM) is a recognized atherosclerotic cardiovascular disease (ACVD) risk factor. This association has yet to be quantified in the Chilean population. AIM: To compare the frequency of ACVD between diabetic and non-diabetic Chilean subjects. MATERIAL AND METHODS: Data was extracted from the Chile National Health Survey (ENS) performed in 2009-2010. DM diagnosis was made with fasting glucose. ACVD (coronary, cerebral and peripheral vascular disease) was established by self-report. Major cardiovascular risk factors were identified by clinical and laboratory assessment. RESULTS: A total of 5,416 adults (2,200 men and 3,216 women) were surveyed in ENS 2009-2010. Of these, 508 were diabetic and 375 reported ACVD. ACVD frequency was 16.1% and 6.1% in diabetic and non-diabetic subjects, respectively. In diabetic men, the frequency of ACVD steadily increased with age, from 5.1% to 22.1%. In diabetic women, the highest frequency of ACVD (17.4%) was found in ages ranging from 45 to 54 years. In people younger than 54 years, the odds ratio for ACVD in diabetic compared to non-diabetic subjects, was 3.59 in men (χ2 = 4.03 p < 0.03) and 5.26 in women (χ2 = 7.7 p < 0.007). Cardiovascular risk factors and metabolic syndrome were significantly more common in diabetic subjects with reported ACVD. CONCLUSIONS: DM is associated with an increased frequency of ACVD and cardiovascular risk factors in Chilean adults. In line with international reports, our findings suggest that DM is also a cardiovascular risk factor in Chile, particularly relevant for women.

[The contribution of Goldstein and Brown to the study of cholesterol metabolism]. / Rememorando la contribución de Goldstein y Brown al estudio del metabolismo del colesterol: a un cuarto de siglo del Premio Nobel de Medicina.

In December 1985, the Nobel Prize of Medicine was awarded to Drs. Joseph L. Goldstein and Michael S. Brown for their fundamental scientific work on the regulation of cholesterol metabolism mediated by the low density lipoprotein receptor pathway. This article briefly reviews the academic and research accomplishments of Drs. Brown and Goldstein as a tribute to these physician-scientists for their well-deserved award and enormous contribution to biomedical science worldwide.

[Cholesteryl ester transfer protein inhibition in the management of atherosclerotic cardiovascular disease: second act "A rebirth of hope"]. / Inhibición de la proteína de transferencia de ésteres de colesterol para el manejo de la enfermedad cardiovascular ateroesclerótica: el segundo acto "Una esperanza que renace"

Despite the clinical use of statins to reduce serum levels of LDL cholesterol and treat atherosclerotic cardiovascular disease, a high proportion of patients remain at significant residual cardiovascular risk. In this context, low HDL cholesterol levels are an additional risk factor and intervention studies suggest that a fraction of the cardiovascular protection achieved with pharmacotherapy is explained specifically by the increase in serum levels of HDL cholesterol. Pharmacological inhibitors of the cholesteryl ester transfer protein (CETP) can induce a significant elevation in HDL cholesterol and, potentially, lead to better control of residual cardiovascular risk beyond the benefit demonstrated by statins. While the use of torcetrapib had unexpected side effects, dalcetrapib and anacetrapib are new CETP inhibitors with a better safety profile and are currently under study to evaluate their effects on vascular lesions and clinical events in patients at high cardiovascular risk. If these studies show positive findings, we will witness a new biomedical advance as significant as was the clinical.

Abdominal obesity is a common finding in normal and overweight subjects of Chile and is associated with increased frequency of cardiometabolic risk factors.

BACKGROUND/OBJECTIVES: Abdominal obesity (AO) is associated with elevated risk for cardiovascular diseases; however, this association is less clear for non-obese people. We estimated the association of AO and cardiovascular risk factors (CVRF) and disease in non-obese adult individuals from Chile. SUBJECTS/METHODS: 5248 adults (15 years of age or older) of both sexes from the Chilean National Health Survey (October 2009 -September 2010, response rate 85%.) were included. Information on myocardial infarction and stroke was self-reported. BMI, waist circumference (WC), arterial pressure, plasma glucose, and cholesterol levels were measured. Predictive accuracy of WC was evaluated by area under curve of receiver operating characteristic analysis and cut off points were established by Youden Index. Relationship between AO and CVRF was analyzed by Chi-squared tests. RESULTS: Normal weight/overweight/obesity were present in 34.4%/45.2%/18.1% of men and 33.4%/33.6%/27.5% of women. Predictive accuracy of WC to identify at least one CVRF was 0.70/0.67 and optimal cutoff points for WC in non-obese subjects were 91/83 cm in men/women, respectively. AO was present in 98.2%/99.1% of obese, 70.5%/77.4% of overweight and 12.4%/16.4% of normal weight men/women. AO was associated with increased frequency of CVRF in overweight men (6/8 and stroke) and women (4/8) and higher frequency in normal weight men (8/8 and myocardial infarction/stroke) and women (6/8 and myocardial infarction). CONCLUSIONS: WC cutoff points calculated for non-obese chilean population discriminate more differences in CVRF in normal weight woman. AO significantly increases the frequency of CVRF and diseases in overweight and especially normal weight individuals. WC can be used as a low cost, feasible and reproducible predictor for CVRF in non-obese individuals in most clinical settings.

Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome.

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1%. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95% CI: 1.68-2.48 and 1.09; 95% CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22% and 36% for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

Egg intake and cardiovascular disease: a scientifi c literature review / Consumo de huevo y enfermedad cardiovascular: una revisión de la literatura científica.

Eggs are a highly nutritive food. They contain high quality protein and several nutrients with potential health benefi ts. Nevertheless, the appearance of cardiovascular disease as an important public health issue, with high morbidity and mortality rates worldwide, along with the identifi cation of high blood cholesterol levels as a risk factor for this disease, was responsible for the advice to limit dietary cholesterol (and, therefore, eggs) that was promoted by health care professionals and institutions during the 70s. To date, several cohort studies show that the intake of one egg a day does not increase cardiovascular risk in the general population. However, this evidence is not clear among diabetic patients, and raises the question whether its consumption in large quantities is entirely safe in this particular population. Additionally, intervention studies have shown that egg consumption does not adversely affect cardiovascular risk factors neither in healthy individuals nor in those with cardiometabolic disease. Moreover, these studies suggest that the incorporation of egg to the diet could bring additional benefits such as promoting a less atherogenic lipid profile.

El huevo es un alimento que aporta proteína de alta calidad y numerosos nutrientes con potenciales beneficios para la salud. Sin embargo, la aparición de la enfermedad cardiovascular como importante causa de morbilidad y mortalidad en el mundo, junto con la identificación de los niveles elevados de colesterol plasmático como factor de riesgo para esta patología, llevó, en los años 70, a profesionales e instituciones de salud a limitar el consumo de colesterol y, por tanto, de huevo en la población. Hasta la fecha, los análisis de cohortes prospectivas tienden a mostrar que el consumo de hasta un huevo diario no aumenta significativamente el riesgo cardiovascular en la población sana. Sin embargo, esta evidencia no es clara en los pacientes diabéticos y pone en duda que este alimento consumido en cantidades elevadas sea del todo inocuo en esta población en particular. Asimismo, estudios de intervención a corto plazo han mostrado que, en general, el consumo de huevo no afecta negativamente los factores de riesgo cardiovascular en individuos sanos así como en aquellos con enfermedad cardiometabólica. Además, estos estudios sugieren que la incorporación del huevo en la dieta podría traer beneficios adicionales, promoviendo un perfil lipídico menos aterogénico.

Physiological and pathological implications of cholesterol.

Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

Retracted: Advances in the physiological and pathological implications of cholesterol.

Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades.

Consumo de huevo y enfermedad cardiovascular: una revisión de la literatura científica / Egg intake and cardiovascular disease: a scientific literature review

El huevo es un alimento que aporta proteína de alta calidad y numerosos nutrientes con potenciales beneficios para la salud. Sin embargo, la aparición de la enfermedad cardiovascular como importante causa de morbilidad y mortalidad en el mundo, junto con la identificación de los niveles elevados de colesterol plasmático como factor de riesgo para esta patología, llevó, en los años 70, a profesionales e instituciones de salud a limitar el consumo de colesterol y, por tanto, de huevo en la población. Hasta la fecha, los análisis de cohortes prospectivas tienden a mostrar que el consumo de hasta un huevo diario no aumenta significativamente el riesgo cardiovascular en la población sana. Sin embargo, esta evidencia no es clara en los pacientes diabéticos y pone en duda que este alimento consumido en cantidades elevadas sea del todo inocuo en esta población en particular. Asimismo, estudios de intervención a corto plazo han mostrado que, en general, el consumo de huevo no afecta negativamente los factores de riesgo cardiovascular en individuos sanos así como en aquellos con enfermedad cardiometabólica. Además, estos estudios sugieren que la incorporación del huevo en la dieta podría traer beneficios adicionales, promoviendo un perfil lipídico menos aterogénico (AU)

Eggs are a highly nutritive food. They contain high quality protein and several nutrients with potential health benefits. Nevertheless, the appearance of cardiovascular disease as an important public health issue, with high morbidity and mortality rates worldwide, along with the identification of high blood cholesterol levels as a risk factor for this disease, was responsible for the advice to limit dietary cholesterol (and, therefore, eggs) that was promoted by health care professionals and institutions during the 70s. To date, several cohort studies show that the intake of one egg a day does not increase cardiovascular risk in the general population. However, this evidence is not clear among diabetic patients, and raises the question whether its consumption in large quantities is entirely safe in this particular population. Additionally, intervention studies have shown that egg consumption does not adversely affect cardiovascular risk factors neither in healthy individuals nor in those with cardiometabolic disease. Moreover, these studies suggest that the incorporation of egg to the diet could bring additional benefits such as promoting a less atherogenic lipid profile (AU)

Consumo de huevo y diabetes mellitus tipo 2: Una revisión de la literatura científica / Egg intake and diabetes mellitus type 2: A review of the scientific literature

RESUMEN El huevo es un alimento altamente nutritivo con potenciales beneficios para la salud. Sin embargo, debido a su elevado contenido de colesterol, su consumo ha sido restringido en la población general. El objetivo de esta revisión es difundir en la comunidad científica la evidencia más reciente sobre los efectos del consumo de huevo específicamente en sujetos con diabetes mellitus. Estudios observacionales muestran que el consumo de hasta un huevo al día no se asocia a una mayor prevalencia de enfermedad cardiovascular en la población general, pero podría aumentar el riesgo entre los diabéticos. Asimismo, algunos de estos estudios han mostrado que un elevado consumo de huevo se asocia a un aumento en la incidencia de diabetes en la población general. Por otro lado, estudios de intervención a corto plazo en este subgrupo muestra que el consumo de huevo no afecta negativamente los factores de riesgo cardiovascular ni control glicémico en estos pacientes. Además, su consumo podría aumentar el impacto del uso de dietas hipocalóricas en la disminución de peso corporal, una importante herramienta en el manejo médico de la diabetes.

ABSTRACT Eggs are a highly nutritious food with potential health benefits. However, because of its high cholesterol content, physicians have recommended consumption restrictions in the general population. The aim of this review is to update the scientific community on the latest research about the impact of egg consumption in subjects with diabetes mellitus. Although several observational studies show that an intake of one egg a day does not increase cardiovascular risk in the general population, however risk may increase among diabetics. Additionally, some prospective cohorts have associated associated higher egg intake with an increased diabetes incidence in the general population. On the other hand, short-term intervention studies have not shown any adverse outcome in terms of cardiovascular risk or glycemic control with egg intake. Moreover, there are studies that suggest a beneficial effect of egg consumption in weight reduction, an important therapeutic tool in diabetes management.

[Physical activity and cardiovascular risk factors among Chilean young men and women]. / Actividad física y su asociación con factores de riesgo cardiovascular: Un estudio en adultos jóvenes.

BACKGROUND: Physical activity (PA) has a protective role in cardiovascular diseases. AIM: To quantify PA in young adults and to correlate it with cardiovascular risk factors. MATERIAL AND METHODS: A cross-sectional study was performed employing the international physical activity questionnaire (IPAQ), to measure the PA of 983 randomly selected young adults from Valparaiso region born between 1974 and 1978. Its results were associated with levels of obesity, insulin resistance and cardiovascular risk factors defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP- ATP III) RESULTS: Mean physical activity among men and women was 3731 ± 3923 and 1360 ± 2303 METs-minutes/week, respectively (p < 0.001). Fifty percent of women and 21.5% of men had an insufficient level of physical activity (p < 0.001). Sixty percent of men and 23.4% of women had an intense level of physical activity (p < 0.001). There was an inverse association of physical activity and insulin resistance. A high physical activity was protective, specially among men, against a low HDL cholesterol level and high triglyceride levels with Odds Ratios of 0.59 (confidence interval (CI): 0,35-0.98) and 0.49 (CI: 0,27-0,87) respectively, after adjusting for body mass index and age. CONCLUSIONS: In this sample, men had higher levels of physical activity, that was protective against insulin resistance and the presence of cardiovascular risk factors.

[The metabolic syndrome: from an aggravating condition to a pathogenic risk factor for chronic diseases]. / El síndrome metabólico: De factor agravante a principal factor de riesgo patogénico en diversas enfermedades crónicas.

In recent years, a rapidly increasing number of studies have focused on the association between metabolic syndrome and several chronic diseases. However, it is difficult to determine a well defined pathogenic relationship, due to the etiological heterogeneity and comorbidities of these diseases. Research efforts are aiming to identify the convergent biological mechanisms that mediate the effects of hyperinsulinemia, hyperglycemia, dyslipidemia, and hypertension. All these conditions define the metabolic syndrome, that increases the risk for several diseases. The knowledge of these biological mechanisms associated with this syndrome will elucidate the pathogenic association between a variety of chronic diseases, including its pathogenic link with cardiovascular diseases and the most common forms of dementia. The development of new therapeutic and preventive strategies for these diseases will be a corollary of this research.

[Prevalence of metabolic syndrome among Chilean adults]. / Prevalencia de sindrome metabólico en población adulta chilena: Datos de la Encuesta Nacional de Salud 2003.

BACKGROUND: There are several diagnostic criteria for Metabolic Syndrome (MS) definition. AIM: To study their application in the Chilean general adult population. MATERIAL AND METHODS: We analyzed data from a random sub sample of 1.833 adults aged 17 years and older surveyed during the First Chilean National Health Survey conducted in 2003. The prevalence of MS was estimated using the update Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF 2005) criteria. The distribution of MS was analyzed according to age, gender, educational level, geographic area, obesity and sedentary lifestyle. RESULTS: The overall prevalence of MS was 31.6% (95% CI 28.5-34.9) and 36.8% (95% CI 33.5-40.3), according to update ATPIII-NCEP and IDF criteria respectively. Both criteria had a 90% concordance. Demographic and socioeconomic distribution was similar for both criteria. The prevalence of high blood pressure, high fasting glucose, and low HDL cholesterol (MS components) were: 46, 22 and 53% respectively. The prevalence of abnormal waist circumference was 30 and 59% according to update ATPIII-NCEP and IDF criteria, respectively. Using update ATPIII-NCEP criteria, the gender, age and educational level adjusted odds ratio (OR) for having MS was 9.59 (95% IC 6.8-13.6) for obese subjects compared with normal weight subjects and 2.14 (95% IC 1.3-3.7) for sedentary subjects compared with non sedentary. CONCLUSIONS: There was a 90% agreement between update ATPIII-NCEP and IDF criteria for the diagnosis of MS. The overall prevalence of MS in this population was 32% usuing update ATPIII-NCEP criteria, with higher prevalence among obese and sedentary subjects.

Asociación entre diabetes mellitus y patología cardiovascular en la población adulta de Chile: estudio de la Encuesta Nacional de Salud 2009-2010 / Association between diabetes mellitus and cardiovascular disease in Chilean adults: Analysis of the national health survey 2009-2010

Background: Diabetes mellitus (DM) is a recognized atherosclerotic cardiovascular disease (ACVD) risk factor. This association has yet to be quantified in the Chilean population. Aim: To compare the frequency of ACVD between diabetic and non-diabetic Chilean subjects. Material and Methods: Data was extracted from the Chile National Health Survey (ENS) performed in 2009-2010. DM diagnosis was made with fasting glucose. ACVD (coronary, cerebral and peripheral vascular disease) was established by self-report. Major cardiovascular risk factors were identified by clinical and laboratory assessment. Results: A total of 5,416 adults (2,200 men and 3,216 women) were surveyed in ENS 2009-2010. Of these, 508 were diabetic and 375 reported ACVD. ACVD frequency was 16.1% and 6.1% in diabetic and non-diabetic subjects, respectively. In diabetic men, the frequency of ACVD steadily increased with age, from 5.1% to 22.1%. In diabetic women, the highest frequency of ACVD (17.4%) was found in ages ranging from 45 to 54 years. In people younger than 54 years, the odds ratio for ACVD in diabetic compared to non-diabetic subjects, was 3.59 in men (χ2 = 4.03 p < 0.03) and 5.26 in women (χ2 = 7.7 p < 0.007). Cardiovascular risk factors and metabolic syndrome were significantly more common in diabetic subjects with reported ACVD. Conclusions: DM is associated with an increased frequency of ACVD and cardiovascular risk factors in Chilean adults. In line with international reports, our findings suggest that DM is also a cardiovascular risk factor in Chile, particularly relevant for women.

Rememorando la contribución de Goldstein y Brown al estudio del metabolismo del colesterol: a un cuarto de siglo del Premio Nobel de Medicina / The contribution of Goldstein and Brown to the study of cholesterol metabolism

Background: In December 1985, the Nobel Prize of Medicine was awarded to Drs. Joseph L. Goldstein and Michael S. Brown for their fundamental scientific work on the regulation of cholesterol metabolism mediated by the low density lipoprotein receptor pathway. This article briefly reviews the academic and research accomplishments of Drs. Brown and Goldstein as a tribute to these physician-scientists for their well-deserved award and enormous contribution to biomedical science worldwide.

Inhibición de la proteína de transferencia de ésteres de colesterol para el manejo de la enfermedad cardiovascular ateroesclerótica: el segundo acto "Una esperanza que renace" / Cholesteryl ester transfer protein inhibition in the management of atherosclerotic cardiovascular disease: second act "A rebirth of hope"

Despite the clinical use of statins to reduce serum levels of LDL cholesterol and treat atherosclerotic cardiovascular disease, a high proportion of patients remain at significant residual cardiovascular risk. In this context, low HDL cholesterol levels are an additional risk factor and intervention studies suggest that a fraction of the cardiovascular protection achieved with pharmacotherapy is explained specifically by the increase in serum levels of HDL cholesterol. Pharmacological inhibitors of the cholesteryl ester transfer protein (CETP) can induce a significant elevation in HDL cholesterol and, potentially, lead to better control of residual cardiovascular risk beyond the benefit demonstrated by statins. While the use of torcetrapib had unexpected side effects, dalcetrapib and anacetrapib are new CETP inhibitors with a better safety profile and are currently under study to evaluate their effects on vascular lesions and clinical events in patients at high cardiovascular risk. If these studies show positive findings, we will witness a new biomedical advance as significant as was the clinical.

[HDL cholesterol: a new target in the treatment of lipid disorders and atherosclerosis?]. / El colesterol HDL: un nuevo objetivo terapéutico en el manejo de las dislipidemias y la ateroesclerosis?

Low plasma HDL cholesterol levels are an independent risk factor for atherosclerotic cardiovascular disease. During the past years, the study of HDL has been stimulated by the discovery of novel genes and proteins, which have provided new insights into the molecular and cellular mechanisms involved in HDL metabolism. In addition, recent clinical studies focused on treating low HDL as primary objective in high cardiovascular risk patients have been very encouraging. Furthermore, new drugs for raising HDL cholesterol are under development. This article reviews the recent progress in the HDL field and its important implications for the pathophysiology and treatment of atherosclerosis. In the near future, we expect that new drugs with specific and beneficial effects on HDL metabolism and the associated cardiovascular risk should improve the current approach to this disease with high burden on health systems and society.

Actividad física y su asociación con factores de riesgo cardiovascular: Un estudio en adultos jóvenes / Physical activity and cardiovascular risk factors among Chilean young men and women

Background: Physical activity (PA) has a protective role in cardiovascular diseases. Aim: To quantify PA in young adults and to correlate it with cardiovascular risk factors. Material and Methods: A cross-sectional study was performed employing the international physical activity questionnaire (IPAQ), to measure the PA of 983 randomly selected young adults from Valparaiso region born between 1974 and 1978. Its results were associated with levels of obesity, insulin resistance and cardiovascular risk factors defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP- ATP III) Results: Mean physical activity among men and women was 3731 ± 3923 and 1360 ± 2303 METs-minutes/week, respectively (p < 0.001). Fifty percent of women and 21.5 percent of men had an insuffcient level of physical activity (p < 0.001). Sixty percent of men and 23.4 percent of women had an intense level of physical activity (p < 0.001). There was an inverse association of physical activity and insulin resistance. A high physical activity was protective, specially among men, against a low HDL cholesterol level and high triglyceride levels with Odds Ratios of 0.59 (confdence interval (CI): 0,35-0.98) and 0.49 (CI: 0,27-0,87) respectively, after adjusting for body mass index and age. Conclusions: In this sample, men had higher levels of physical activity, that was protective against insulin resistance and the presence of cardiovascular risk factors.