© 1995 American Heart Association, Inc.
Articles |
Lowering of HDL2b by Probucol Partly Explains the Failure of the Drug to Affect Femoral Atherosclerosis in Subjects With Hypercholesterolemia
A Probucol Quantitative Regression Swedish Trial (PQRST) Report
From the King Gustaf V Research Institute, Karolinska Hospital, Stockholm (J.J., L.S.E., G.W.); Research Centre of General Medicine, North Western Health Board, Stockholm County Council (J.J.); Department of Internal Medicine, University Hospital, Linköping (A.G.O., J.M.); Department of Diagnostic Radiology, University Hospital, Uppsala (L.B., S.N., U.E.), Sweden; and the Life Insurance Companies Institute for Medical Statistics, Ullevål Hospital, Oslo, Norway (I.H.).
Correspondence to Jan Johansson, MD, PhD, Research Centre of General Medicine, Borgmästarvillan–Karolinska Hospital, S-171 76 Stockholm, Sweden.
Abstract The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n=303) was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine (8 g BID) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic (>6.86 mmol/L) subjects. Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery. In this report we studied in a representative subgroup (n=72) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL particle size subclasses. Probucol lowered the relative level of HDL2b, comprising the largest HDL particles, by 53% and the protein concentration of HDL2b by 67%. The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety. The change in lumen volume correlated significantly with change in HDL, ie, HDL cholesterol (r=.34, P<.01), HDL2 cholesterol (r=.37, P<.01), HDL2b protein (r=.44, P<.001), and the relative HDL2b value (r=.51, P<.001). The corresponding values for relative HDL2b distribution calculated on the active (n=35) and placebo (n=37) groups separately were also significant (r=.39 and .32, respectively; both P<.05). The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction. HDL2b lowering was highly significantly correlated to probucol concentration. We suggest that the lowering effects of probucol on HDL and particularly on the HDL2b fraction at least in part explain why regression of femoral atherosclerosis was not obtained by the drug.
Key Words: high-density lipoprotein particle size • atherosclerosis • arteriography • cholestyramine and antioxidation
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