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.

• Authors: Hayato Tada, Junji Kobayashi, Masa-Aki Kawashiri, Kazuya Miyashita, Atsushi Nohara, Akihiro Inazu, Katsuyuki Nakajima, Hiroshi Mabuchi, Masakazu Yamagishi
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 15 Pg. 66 (Apr 02 2016) ISSN: 1476-511X [Electronic] England
• PMID: 27039080 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Imidazoles
• Receptors, LDL
• Resins, Synthetic
• colestimide
• Epichlorohydrin
• Rosuvastatin Calcium
• LIPG protein, human
• Lipase
• LPL protein, human
• Lipoprotein Lipase
• Ezetimibe

Topics

• Adult
• Aged
• Anticholesteremic Agents (therapeutic use)
• Drug Therapy, Combination (methods)
• Epichlorohydrin (therapeutic use)
• Ezetimibe (therapeutic use)
• Female
• Humans
• Hyperlipoproteinemia Type II (drug therapy, enzymology)
• Imidazoles (therapeutic use)
• Lipase (blood)
• Lipoprotein Lipase (blood)
• Male
• Middle Aged
• Receptors, LDL (genetics)
• Resins, Synthetic (therapeutic use)
• Rosuvastatin Calcium (therapeutic use)