Effects of Nicotinic Acid Therapy on Plasma High Density Lipoprotein Subfraction Distribution and Composition and on Apolipoprotein A Metabolism

This report describes the effects of pharmacologic doses (3 g/d) of nicotinic acid on the plasma distribution and chemical composition of the high density lipoprotein (HDL) subfractions HDL₂ and HDL₃ and examines the influence of the drug on the metabolism of the major HDL apoproteins, apolipoproteins A-I (ApoA-I) and A-II (Apo-II).

The drug lowered plasma cholesterol (15%, P < 0.05) and triglyceride (27%, P < 0.01); the former effect a result of a fall in the amount of cholesterol associated with very low density lipoproteins (31%, P < 0.02) and low density lipoproteins (36%, P < 0.02). Conversely, it raised plasma HDL cholesterol (23%, P < 0.05) and increased (by 345%) the plasma HDL₂:HDL₃ ratio. The latter derived from an absolute increment (646%) in circulating HDL₂, coupled with a fall (47%) in HDL₃. This change was not associated with major alterations in the overall cholesterol (free and esterified), triglyceride, phospholipid, or protein content of the subfractions; however, it was accompanied by substantial changes in their protein composition. In particular, the molar ratio of ApoA-I:ApoA-II in HDL₃ declined from 2.7:1 to 2.1:1 during nicotinic acid treatment.

Significant perturbations of ApoA-I and ApoA-II metabolism accompanied the drug-induced HDL subfraction redistribution. Specifically, the plasma concentration of ApoA-I rose by 7% (P < 0.05) because of a decrease in its fractional catabolic rate. Moreover, whereas before treatment 6 and 94% of the plasma ApoA-I circulated with HDL₂ and HDL₃, after commencement of nicotinic acid therapy this distribution became 49 and 51% in HDL₂ and HDL₃, respectively. ApoA-II was found mainly in HDL₃, both before and during nicotinic acid treatment. Administration of the drug caused a 14% reduction in its plasma concentration (P < 0.05), which derived principally from a fall (22%, P < 0.01) in its synthetic rate.

These data suggest that the effects of nicotinic acid on the HDL subfraction distribution may be mediated via (a) net transfer of ApoA-I from HDL₃ to HDL₂ and (b) a reduction in ApoA-II synthesis. Our present understanding of the association between HDL and atherosclerosis indicates that such changes may have prophylactic value in the prevention of coronary artery disease.

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