| Grant number: | 12/18044-1 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | December 01, 2012 |
| End date: | November 30, 2014 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Andrei Carvalho Sposito |
| Grantee: | Valéria Nasser Figueiredo |
| Host Institution: | Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
Abstract Over the last four decades, niacin treatment of the atherogenic lipid profile and the incidence of cardiovascular events has been evaluated in numerous other studies, with contradictory results which suggest that different clinical phenotypes can influence the efficacy this treatment. The study was based on the divergence of results and was designed based on two assumptions. The first hypothesis: a frequent adverse effect in patients receiving niacin is the development of significant cutaneous warmth and facial vasodilatation that can cause of treatment discontinuation (50%). This effect is due to increased prostaglandin D2 synthesis (PGD2) which in large quantities can causes widespread vasodilatation with severe hypotension. Recent studies have elucidated the molecular mechanism that mediates niacin-induced flushing: Niacin acting through the G protein-coupled receptor GPR109A stimulates the production of several prostaglandins, including PGE2 and PGD2, in mast cells, keratinocytes and monocytes/macrophages. Particularly, PGD2 acting through the DP receptor has been alleged to cause the niacin-induced flush. Consequently, a combination of the DP receptor antagonist laropiprant with niacin is currently marketed for treatment of dyslipidemias. However, it is plausible that the laropiprant is used in combination with niacin to reduce this side effect. However, no studies have evaluated this influence. The first hypothesis was evaluated by a short-term study (Phase 1) in which we compared the systemic arterial pressure and brachial artery reactivity in patients taking niacin and niacin with Laropiprant. Our second hypothesis is based on the interaction between the lipid phenotype and the effects of niacin therapy on cardiovascular health. There are several mechanisms by which treatment with niacin may interact with lipid metabolism and attenuate atherogenesis. This includes its effects on hepatic synthesis and metabolism of apolipoprotein A-I. However, it is estimated that the effect on HDL cholesterol concentrations is due to reduced availability of triglyceride-rich lipoproteins (they substrate they act on the exchange cholesterol esters in HDL by the action of cholesterol ester transfer protein). Thus, it is plausible to expect that not just the amount of HDL but also function of HDL modify between individuals with and without hypertriglyceridemia treated with niacin. The second study we will evaluate the hypothesis that the role of triglyceridemia in patients with hypoalphalipoproteinemia, with or without hypertriglyceridaemia on treatment with niacin. We will analyze the effect of treatment on functional and phenotypic changes in HDL. | |
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