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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:236-249.)
© 1996 American Heart Association, Inc.

Articles

Effects of Colestipol Alone and in Combination With Simvastatin on Apolipoprotein B Metabolism

Allan Gaw; Christopher J. Packard; Grace M. Lindsay; Elizabeth F. Murray; Bruce A. Griffin; Muriel J. Caslake; Ian Colquhoun; David J. Wheatley; A. Ross Lorimer; James Shepherd

From the Institute of Biochemistry (A.G., C.J.P., G.M.L., E.F.M., B.A.G., M.J.C., J.S.), Department of Cardiac Surgery (I.C., D.J.W.), and the Department of Medical Cardiology (A.R.L.), Glasgow Royal Infirmary, Glasgow, UK.

Correspondence to Dr A. Gaw, Department of Pathological Biochemistry, Royal Infirmary University/NHS Trust, Glasgow G31 2ER, UK.

Abstract The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol 6.5 mmol/L [250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P<.001) and LDL cholesterol (LDL-C) by 23% (P<.001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P<.001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P<.05) that was largely due to a fall in the clearance rate of VLDL₁ apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL₂ to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P=.01) and LDL (37%, P<.04) apoB pools due to enhanced clearance of IDL (214%, P<.03) and reduced total input of LDL (39%, P<.003).

Key Words: VLDL turnover • bile acid sequestrant resin • 3-hydroxy-3-methylglutaryl coenzyme A–reductase inhibitor

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