Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy

Abstract

Background: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs.

Methods: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added.

Results: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4-124.7] to 67.5 [IQR: 62.1-114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1-114.3] to 70.2 [IQR: 58.3-106.2], and to 74.9 [IQR: 55.6-101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7-288.7] to 297.0 [IQR: 266.2-300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level.

Conclusion: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently.

Keywords: Endothelial lipase; Familial hypercholesterolemia; Lipoprotein lipase.

Fig. 1

Study design. The present study was conducted as a prospective open randomized study to investigate the efficacy and safety of coadministration of rosuvastatin at 20 mg/day, ezetimibe at 10 mg/day, and granulated colestimide at 3.62 g/day. Any lipid-lowering agents had been washed out ≥ 4 weeks before entry into the study. Study subjects were divided into two groups by an envelope-based method to elucidate the secondary end point of the present study: rosuvastatin at 20 mg/day (group 1) versus rosuvastatin at 10 mg/day coadministered with ezetimibe at 10 mg/day (group 2). The white, blue, pink, and purple arrows indicate baseline, second, third, and last blood sampling, respectively

Fig. 2

Lipase mass concentration during coadministration of three drugs in group 1. a  LPL mass concentration. b  EL mass concentration. White indicates the baseline. Blue indicates the second blood sampling when rosuvastatin was administered at 20 mg/day. Pink indicates the third blood sampling when rosuvastatin at 20 mg/day and ezetimibe at 10 mg/day were coadministered. Purple indicates the last blood sampling when rosuvastatin at 20 mg/day, ezetimibe at 10 mg/day, and colestimide at 3.62 g/day were coadministered

Fig. 3

Lipase mass concentration during coadministration of three drugs in group 2. a  LPL mass concentration. b  EL mass concentration. White indicates the baseline. Blue indicates the second blood sampling when rosuvastatin at 10 mg/day and ezetimibe at 10 mg/day were coadministered. Pink indicates the third blood sampling when rosuvastatin at 20 mg/day and ezetimibe at 10 mg/day were coadministered. Purple indicates the last blood sampling when rosuvastatin at 20 mg/day, ezetimibe at 10 mg/day, and colestimide at 3.62 g/day were coadministered