Effects of atorvastatin on the clearance of triglyceride-rich lipoproteins in familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCHL) patients have an impaired catabolism of postprandial triglyceride (TG)-rich lipoproteins (TRLs). We investigated whether atorvastatin corrects the delayed clearance of large TRLs in FCHL by evaluating the acute clearance of Intralipid (10%) and TRLs after oral fat-loading tests. Sixteen matched controls were included. Atorvastatin reduced fasting plasma TG (from 3.6 +/- 0.4 to 2.5 +/- 0.3 mM; mean +/- SEM) without major effects on fasting apolipoprotein B48 (apoB48) and apoB100 in large TRLs. Atorvastatin significantly reduced fasting intermediate density lipoprotein (Svedberg flotation, 12-20)-apoB100 concentrations. After Intralipid, TG in plasma and TRL showed similar kinetics in FCHL before and after atorvastatin treatment, although compared with controls, the clearance of large TRLs was only significantly slower in untreated FCHL, suggesting an improvement by atorvastatin. Investigated with oral fat-loading tests, the clearance of very low density lipoprotein (Sf20-60)-apoB100 improved by 24%, without major changes in the other fractions. The most striking effects of atorvastatin on postprandial lipemia in FCHL were on hepatic TRL, without major improvements on intestinal TRLs. Fasting plasma TG should be reduced more aggressively in FCHL to overcome the lipolytic disturbance causing delayed clearance of postprandial TRLs.
|Keywords||Administration, Oral, Adult, Apolipoproteins B/blood, Cholesterol/blood, Fat Emulsions, Intravenous/pharmacology, Fats/administration & dosage/pharmacology, Female, Heptanoic Acids/*therapeutic use, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use, Hyperlipidemia, Familial Combined/*blood/*drug therapy, Lipoproteins/*antagonists & inhibitors/blood, Male, Middle aged, Pyrroles/*therapeutic use, Research Support, Non-U.S. Gov't, Triglycerides/*antagonists & inhibitors/blood/pharmacokinetics|
|Persistent URL||dx.doi.org/10.1210/jc.2003-031329, hdl.handle.net/1765/13592|
Castro Cabezas, M., Verseyden, C., Meijssen, S., Jansen, H., & Erkelens, D.W.. (2004). Effects of atorvastatin on the clearance of triglyceride-rich lipoproteins in familial combined hyperlipidemia.. Journal of Clinical Endocrinology and Metabolism, 89(12), 5972–5980. doi:10.1210/jc.2003-031329