The Effects of Niacin on Lipoprotein Subclass Distribution

John M. Morgan, MD; Christina M. Carey, PA-C; Anne Lincoff, MD; David M. Capuzzi, MD, PhD

Disclosures
In This Article

Abstract and Introduction

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution. A MEDLINE search was conducted for clinical studies reporting the effects of niacin on lipoprotein subclasses. The niacin-associated elevations in HDL cholesterol likely stem from differential drug effects on subclasses, producing favorable changes in levels of HDL2 and apolipoprotein A-I. Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses. In addition, it also tends to decrease concentrations of the larger very-low-density lipoprotein subclasses. Niacin confers diverse benefits with respect to both the quantity and quality of lipid and lipoprotein particles.

Epidemiologic evidence has long suggested that elevated serum levels of low-density lipoprotein (LDL) cholesterol and triglycerides (TG), as well as low levels of high-density lipoprotein (HDL) cholesterol, increase the risk of coronary heart disease (CHD).[1] Moreover, decades of randomized, controlled trials have shown that lipid-modifying therapies, notably the statins, significantly reduce the rates of primary and secondary cardiovascular events by approximately 25%-35% compared with placebo.[2,3] Nonetheless, cardiovascular risk in treated patients remains significant.

Dyslipidemia is a heterogeneous metabolic condition that involves a complex, interacting array of lipids and lipoproteins with varying influence on CHD risk.[4,5] LDL, HDL, and very-low-density lipoprotein (VLDL) represent families of lipoprotein particles that differ in size, composition, and density and also vary in atherogenicity. It is therefore not surprising that drug therapy aimed at total lipid levels, which actually encompass a range of lipoprotein subclasses collectively measured by typically undiscriminating assays, may often fail to maximize risk reduction. More successful would be an agent or combination of agents that has favorable effects on subclasses and total lipid levels.

The lipid-modifying effects of niacin at pharmacologic dosages have been recognized for more than a half-century. Niacin has been shown to improve concentrations of all lipid-related CHD risk factors; it is the most powerful agent currently available for raising HDL cholesterol and also lowers TG, LDL cholesterol, and lipoprotein(a).[1] It has also been shown to favorably influence the distribution of HDL, LDL, and VLDL sub-classes.[6,7,8] Moreover, niacin therapy, alone or combined with other agents, has been associated with reversal of angiographic coronary artery disease progression and reductions in cardiovascular morbidity and mortality.[9,10,11]

The increasing recognition of the importance of the lipid and lipoprotein subclasses in the atherogenic process is leading to renewed interest in the multidimensional properties of niacin. Therefore, it is timely to review the effects of niacin on lipoprotein subclasses.

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