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Treatment effect of niacin on HDL metabolism and endothelial function in patients with low HDL with or without hypertriglyceridemia

Grant number: 11/20300-3
Support type:Regular Research Grants
Duration: July 01, 2012 - June 30, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Andrei Carvalho Sposito
Grantee:Andrei Carvalho Sposito
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

It is estimated a worldwide burden of about 200 million people presenting acute or chronic manifestations of atherosclerosis. Despite the undoubted benefit of reducing low density lipoprotein cholesterol (LDL) plasma levels, even in subjects who achieve optimal levels of reduction, a residual risk of 55% remains. In parallel, the most frequently found dyslipidemia in individuals with atherosclerotic disease is the decreased high density lipoprotein (HDL) cholesterol plasma levels, or hipoalfalipoproteinemia. HDL has been consistently associated with protection against atherogenesis in epidemiological, translational, in animal models and in vitro studies. Based on these assumptions, the elevation of plasma HDL has been pursued as a possibility to mitigate the residual risk. Nevertheless, contradictory results have been observed in studies using drugs aiming to raise HDL cholesterol levels, including nicotinic acid (niacin or vitamin B3). Among the possibilities for such divergence of the results, stands the inclusion of patients with different pathophysiology and, therefore, different kinds of association with atherogenesis and response to therapies. In fact, hipoalfalipoproteinemia in the presence or absence of hypertriglyceridemia present pathophysiology, atherogenicity and response to niacin or fibrate quite distinct. While in individuals with hypertriglyceridemia, enhanced catabolism of HDL is the cause more prominent for hypoalfalipoproteinemia, in those without hypertriglyceridemia deficient HDL synthesis is the main cause. Consistent with this hypothesis, subanalysis of the aforementioned studies which considered only patients with hipoalfalipoproteinemia associated with increased triglyceride (TG) levels found clinical benefit with the drug treatment. In the present study, we aim to evaluate the response to the treatment with niacin on patients with hipoalfalipoproteinemia, with or without elevated TG. We aim to evaluate the effect of this treatment on the phenotypic and functional changes of HDL particles and its impact on systemic inflammatory activity, the plasma content of nitric oxide and endothelium-dependent vasodliation. (AU)