ABSTRACT
INTRODUCTION: Much evidence indicates the importance of the endothelium and hypercholesterolemia in atherosclerosis, as well as the decline in endothelial function with aging. However, it is unclear if treating dyslipidemia in elderly patients improves endothelial function and reduces C-reactive protein levels. OBJECTIVES: To evaluate vasomotor function, lipids and C-reactive protein in mildly hypertensive and hypercholesterolemic elderly patients treated with atorvastatin. METHODS: Forty-seven elderly Brazilian subjects (> 65 years old) with LDL cholesterol (LDL-c) > 130 mg/dL were randomly assigned, in a double-blinded manner, to receive either placebo (n = 23) or 20 mg/day of atorvastatin (n = 24) for 4 weeks. Exclusion criteria included diabetes, serious hypertension, obesity, steroid use, hormone replacement, and statin use within the previous six months. All patients underwent clinical examinations, laboratory tests (glucose, lipids, liver enzymes, creatine phosphokinase and high sensitivity C-reactive protein) and assessment of vasomotor function by high-resolution ultrasound examination of the brachial artery (flow-mediated dilation and sublingual nitrate), both before and after treatment. RESULTS: The patients were 65 to 91 years old; there was no significant difference between basal flow-mediated dilation of placebo (7.3 ± 6.1 percent) and atorvastatin (4.5 ± 5.1 percent; p = 0.20). The same was observed after treatment (6.6 ± 6.2 vs. 5.0 ± 5.6; p = 0.55). The initial nitrate dilatation (8.1 ± 5.4 percent vs. 10.8 ± 7.5 percent; p = 0.24) and that after 4 week treatment (7.1 ± 4.7 percent vs. 8.6 ± 5.0 percent; p = 0.37) were similar. Atorvastatin produced a reduction of 20 percent of the C-reactive protein and 42 percent in the LDL-c; however, there were no changes in the flow-mediated dilation. CONCLUSIONS: Atorvastatin produced a significant change of lipids and C-reactive protein; however, there were no changes in vasomotor ...
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Anticholesteremic Agents/therapeutic use , C-Reactive Protein/analysis , Endothelium, Vascular/drug effects , Heptanoic Acids/therapeutic use , Lipids/blood , Pyrroles/therapeutic use , Vasodilation/drug effects , Anticholesteremic Agents/metabolism , Blood Flow Velocity , C-Reactive Protein/metabolism , Cholesterol, LDL/blood , Double-Blind Method , Heptanoic Acids/metabolism , Hypercholesterolemia/drug therapy , Hypercholesterolemia/metabolism , Hypercholesterolemia/physiopathology , Hypertension/drug therapy , Hypertension/metabolism , Hypertension/physiopathology , Pyrroles/metabolism , Regional Blood Flow/physiology , Severity of Illness IndexABSTRACT
Os fibratos são as drogas de escolha nas hipertrigliceridemias. Após sua absorção, os fibratos são metabolizados pelo fígado, utilizando isoenzimas P450 não compartilhadas pelas estatinas. Entretanto, para alguns fibratos, como o genfibrozil, uma interação com estatinas pode ocorrer durante a sua glucuronidação, ou pelo deslocamento de frações livres de estatina ligadas às proteínas plasmáticas. A vida-média plasmática é variável entre os fibratos (2-80 h). Recentemente, foi demonstrado que os fibratos promovem suas ações lipídicas pelo estímulo dos PPAR-alfa. Através dessa ação, existe um incremento na transcrição de alguns genes relacionados com o metabolismo lipídico, como a LLP, APOAI, APOAII, ABCA-1, bem como uma diminuição na expressão da APOCIII, e muitas outras ações.
Subject(s)
Humans , Anticholesteremic Agents/pharmacology , Clofibrate/pharmacology , Anticholesteremic Agents/metabolism , Clofibrate/metabolism , Lipid Metabolism/drug effectsABSTRACT
Los fitoesteroles y sus formas reducidas, los fitoestanoles, son esteroles de origen vegetal ampliamente distribuidos en la naturaleza y cuya estructura es muy similar a la del colesterol. Desde hace años se conoce que estos esteroles producen efectos hipocolesterolémicos cuando son ingeridos en el rango de 1-3 g/día, por lo cual se les considera como importantes aliados en la prevención de las enfermedades cardiovasculares, siendo su consumo indicado para individuos con hipercolesterolemias leves o moderadas. El efecto hipocolesterolémico de los fitoesteroles y de los fitoestanoles es atribuido a tres acciones metabólicas: inhiben la absorción intestinal de colesterol por competencia en la incorporación del colesterol a las micelas mixtas; disminuyen la esterificación del colesterol en los enterocitos al inhibir la actividad de la enzima acilCoA-colesterol-acil transferasa, y; estimulan el eflujo de colesterol desde los enterocitos hacia el lumen intestinal al aumentar la actividad y la expresión de un transportador de tipo ABC. La acción conjunta de los esteroles y/o estanoles sobre estos mecanismos produce una disminución del colesterol total plasmático y del colesterol-LDL, sin modificar los niveles del colesterol-HDL. Los fitoesteroles y fitoestanoles constituyen un modelo muy adecuado para el desarrollo de alimentos funcionales. Actualmente en diferentes países se comercializan leches, jugos, yogurt y margarinas que contienen ya sea fitoesteroles o fitoestanoles.