There is increasing evidence that
high-density lipoprotein (HDL) and its subfractions are protective against atherosclerotic
cardiovascular disease. Physical exercise,
weight reduction, smoking cessation,
diabetes mellitus control, and specific drugs, including
niacin,
fibrates, and
estrogens, are effective methods to increase HDL levels.
Niacin is the oldest and most powerful clinical agent for raising HDL levels. Niaspan, an extended-release
niacin formulation, is as potent as immediate-release
niacin in increasing levels of
HDL cholesterol; subfractions HDL2 and HDL3;
apolipoprotein A-I, the major
protein of HDL, and its cardioprotective subfraction
lipoprotein A-I. Recent research from our laboratory suggests a novel mechanism by which
niacin inhibits hepatic removal of HDL-
apoprotein A-I without interfering with the removal of
cholesterol carried by HDL, thus augmenting reverse
cholesterol transport. Other mechanistic studies indicate that
fibrates and
estrogens stimulate the synthesis and production of HDL-
apoprotein A-I. Because
niacin decreases HDL-
apoprotein A-I removal, and
fibrates and
estrogens increase HDL-
apoprotein A-I production, combinations of
niacin with these agents may raise HDL levels more than
fibrates or
estrogens alone.