Circulation, Vol 80, 1313-1319, Copyright © 1989 by American Heart Association
GM Kostner, D Gavish, B Leopold, K Bolzano, MS Weintraub and JL Breslow
Lp(a) is a plasma lipoprotein particle consisting of a plasminogenlike
protein [apo(a)] disulfide bonded to the apo B moiety of low-density
lipoprotein (LDL). Increased plasma levels of Lp(a), either independently
or interactively with LDL levels, have been shown to be a risk factor for
atherosclerosis. Recently, a new class of lipid- lowering drugs, HMG CoA
reductase inhibitors, have been introduced. These drugs act by decreasing
liver cholesterol synthesis resulting in up-regulation of LDL receptors,
increased clearance of LDL from plasma, and diminution of plasma LDL
levels. In this study, we examined the effect of HMG CoA reductase
inhibitors on Lp(a) levels in three groups of subjects, five volunteers and
two groups of five and 14 patients. In all 24 subjects, mean decreases were
observed in total cholesterol (43 +/- 5%), total triglyceride (35 +/- 8%),
very low-density lipoprotein (45 +/- 9%), and LDL cholesterol (43 +/- 5%).
The mean change in high- density lipoprotein cholesterol was an increase of
7 +/- 8%. Despite the very significant decrease in LDL cholesterol levels
(p less than 0.001), Lp(a) levels increased by 33 +/- 12% (p less than
0.005). This was not associated with a measurable change in the chemical
composition or size of the Lp(a) particle. This emphatically suggests that
Lp(a) particles, despite consisting principally of LDL, are cleared from
plasma differently than LDL. The surprising finding of an increase in Lp(a)
levels suggests this class of drugs may have a direct effect on Lp(a)
synthesis or clearance independent of its effect on LDL receptors.
ARTICLES
HMG CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels
Graz University, Austria.
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