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Effect of niacin on HDL cholesterol and endothelial function in patients with low HDL cholesterol levels with or without hypertriglyceridaemia

Grant number: 12/18044-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2012
Effective date (End): November 30, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Andrei Carvalho Sposito
Grantee:Valéria Nasser Figueiredo
Home 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.

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MODOLO, RODRIGO; FIGUEIREDO, VALERIA N.; MOURA, FILIPE A.; ALMEIDA, BRENO; QUINAGLIA E SILVA, JOSE C.; NADRUZ, JR., WILSON; LEMOS, PEDRO A.; COELHO, OTAVIO R.; BLAHA, MICHAEL J.; SPOSITO, ANDREI C.; GRP, BRASILIA HEART STUDY. Coronary artery calcification score is an independent predictor of the no-reflow phenomenon after reperfusion therapy in acute myocardial infarction. Coronary Artery Disease, v. 26, n. 7, p. 562-566, NOV 2015. Web of Science Citations: 4.
MOURA, FILIPE A.; FIGUEIREDO, VALERIA N.; TELES, BRUNA S. B. S.; BARBOSA, MEYRIANNE A.; PEREIRA, LARA R.; COSTA, ANA P. R.; CARVALHO, LUIZ SERGIO F.; CINTRA, RIOBALDO M. R.; ALMEIDA, OSORIO L. R.; QUINAGLIA E SILVA, JOSE C.; NADRUZ JUNIOR, WILSON; SPOSITO, ANDREI C.; STUDY, BRASILIA HEART. Glycosylated hemoglobin is associated with decreased endothelial function, high inflammatory response, and adverse clinical outcome in non-diabetic STEMI patients. ATHEROSCLEROSIS, v. 243, n. 1, p. 124-130, NOV 2015. Web of Science Citations: 11.
SCHERR, CARLOS; FIGUEIREDO, VALERIA N.; MOURA, FILIPE A.; SPOSITO, ANDREI C. Not Simply a Matter of Fish Intake. CURRENT VASCULAR PHARMACOLOGY, v. 13, n. 5, p. 676-678, 2015. Web of Science Citations: 1.
CARVALHO, LUIZ SERGIO F.; VIRGINIO, VITOR W. M.; PANZOLDO, NATALIA B.; FIGUEIREDO, VALERIA N.; SANTOS, SIMONE N.; MODOLO, RODRIGO G. P.; ANDRADE, JOALBO M.; QUINAGLIA E SILVA, JOSE C.; NADRUZ-JUNIOR, WILSON; DE FARIA, ELIANA C.; SPOSITO, ANDREI C.; GRP, BRASILIA HEART STUDY. Elevated CETP activity during acute phase of myocardial infarction is independently associated with endothelial dysfunction and adverse clinical outcome. ATHEROSCLEROSIS, v. 237, n. 2, p. 777-783, DEC 2014. Web of Science Citations: 15.
MOURA, FILIPE A.; CARVALHO, LUIZ SERGIO F.; CINTRA, RIOBALDO M. R.; MARTINS, NAIARA V.; FIGUEIREDO, VALERIA N.; QUINAGLIA E SILVA, JOSE C.; ALMEIDA, OSORIO L. R.; COELHO, OTAVIO R.; SPOSITO, ANDREI C. Validation of surrogate indexes of insulin sensitivity in acute phase of myocardial infarction based on euglycemic-hyperinsulinemic clamp. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 306, n. 4, p. E399-E403, FEB 2014. Web of Science Citations: 8.
FIGUEIREDO, VALERIA N.; DE SOUZA GODOI, FILIPE CANELA; MARTINS, NESTOR S.; QUINAGLIA E SILVA, JOSE C.; NADRUZ, JR., WILSON; COELHO, OTAVIO R.; SPOSITO, ANDREI C.; GRP, BRASILIA HEART STUDY. Diabetes mellitus unawareness is a strong determinant of mortality in patients manifesting myocardial infarction. CURRENT MEDICAL RESEARCH AND OPINION, v. 29, n. 11, p. 1423-1427, NOV 2013. Web of Science Citations: 3.

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