Effect of Extended‐Release Niacin on High‐Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin‐Treated Patients

Abstract

BackgroundThe aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment.Methods and ResultsIn a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity.ConclusionsERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01054508.

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

“…164 Moreover, extended-release niacin when added to statin monotherapy resulted in lowering of lipoprotein(a) and oxidized LDL as well as the inflammatory markers SAA and monocyte chemoattractant protein-1. 165 As a consequence, like statins, also niacin has attracted research interest as a therapeutic candidate for modifying HDL structure and function. In fact, mass spectrometry-based proteome analysis revealed that 1 year combination treatment with atorvastatin (10 to 20 mg daily) plus extended-release niacin (2 g daily) in CAD patients remodeled the protein composition of HDL3 particles toward that of healthy control subjects.…”

“…No differences were observed in the protective effects of HDL against LDL oxidation between dyslipidemic patients treated with extended-release niacin/laropiprant on top of statin therapy and those treated with statin monotherapy. 165 An intervention study in patients with dyslipidemia found no significant change in serum cholesterol efflux capacity after 6 weeks of extended-release niacin therapy (titrated up to 1 g/day). 170 Similarly, adding niacin (2 g daily) to simvastatin therapy provided no additional benefit with regard to cholesterol efflux capacity and HDL inflammatory index in patients with carotid atherosclerosis, despite increasing HDL-cholesterol by 29%.…”

Treating multiple antiaging pathways improves health markers in open label clinical study

“…3 also includes a comparison to the HDL Cholesterol increase found in a clinical trial with Extended Release Niacin (ERN in Fig. 3), which raised HDL Cholesterol 18% (p < 0.001) in this trial [71].…”

“…Total Cholesterol (TC) and blood glycosylated hemoglobin (HbA1c) levels were also tested in the [70], and Extended Release Niacin (ERN at 1500 mg/day for 6 weeks, N = 27), which is taken from a placebo-ERN crossover clinical trial [71]. All stared results are significant with p < 0.05 subjects at baseline and after 15 weeks of SC100+.…”

Impacto de la dieta mediterránea sobre las lipoproteínas de alta densidad

“…Por lo tanto, el desarrollo farmacológico centrado en las lipoproteínas HDL no debiera enfocarse exclusivamente en la búsqueda de nuevas drogas que aumenten los niveles de colesterol HDL, sino que, además, mejoren las capacidades funcionales de las partículas de HDL. Por ejemplo, el ácido nicotínico no sólo incrementa las cifras de colesterol HDL, sino que también mejora la acción de las partículas de HDL como aceptoras de colesterol durante el eflujo celular de este lípido 11,12 . Por otro lado, nuevos fármacos en desarrollo -como los inhibidores de la proteína de transferencia de ésteres de colesterol (CETP) que elevan los niveles de colesterol HDL-también aumentan la capacidad funcional intrínseca de las partículas de HDL en el proceso de eflujo celular de colesterol 13,14 , aunque todavía no se ha demostrado su real beneficio clínico en la reducción de eventos cardiovasculares.…”