Effect of ileal exclusion on kinetics of very low density lipoprotein triglycerides in familial hypercholesterolemia

Abstract

Plasma lipoproteins, VLDL triglyceride kinetics, and bile acid and cholesterol synthesis were measured in 21 patients heterozygous for familial hypercholesterolemia with ( n = 11) or without ( n = 10) ileal bypass. LDL cholesterol and apoprotein B concentrations were lower, and cholesterol and bile acid synthesis, the VLDL triglyceride/cholesterol ratio, and the HDL cholesterol concentration were higher in the operated than the control patients. The VLDL triglyceride production rate was increased in the operated normotriglyceridemic patients by about 65%, whereas the fractional catabolism of VLDL triglycerides and the calculated VLDL cholesterol transport were similar in the operated and control groups. VLDL triglyceride production was not correlated with cholesterol or bile acid synthesis. The VLDL triglyceride concentration was positively correlated with the production and negatively with the fractional catabolism of VLDL triglycerides. In unoperated normotriglyceridemic patients the VLDL triglyceride production was positively correlated with LDL cholesterol ( r = 0.69, p < 0.05), LDL triglyceride ( r = 0.84, p < 0.01) and LDL apoprotein B ( r = 0.80, p < 0.01) concentrations, and with the LDL triglyceride/apoprotein B ( r = 0.72, p < 0.05) and LDL triglyceride/cholesterol ( r = 0.68, p < 0.05) ratios. None of these correlations was significant in the operated patients. We conclude that in heterozygous familial hypercholesterolemia (1) VLDL triglyceride level depends on both VLDL triglyceride synthesis and catabolism, (2) LDL level is proportionate to VLDL triglyceride production in the unoperated patients but not in the patients with ileal bypass, (3) ileal exclusion results in an increase in the production rate of VLDL triglycerides in normotriglyceridemic patients but otherwise VLDL triglyceride production is poorly associated with cholesterol and bile acid synthesis, (4) ileal exclusion may induce hepatic secretion of triglyceride-rich VLDL.