Abstract
BackgroundThe influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood. We compared the effect of two lipid-lowering strategies on HDL functions and identified some HDL-related proteins.MethodsThirty two patients were initially screened and HDLs of 21 patients were finally analyzed. Patients were randomized to receive atorvastatin 20 mg (n = 11) or atorvastatin 5 mg/ezetimibe 10 mg combination (n = 10) for 8 weeks. The cholesterol efflux capacity and other anti-inflammatory functions were assessed based on HDLs of the participants before and after treatment. Pre-specified HDL proteins of the same HDL samples were measured.ResultsThe post-treatment increase in cholesterol efflux capacities was similar between the groups (35.6% and 34.6% for mono-therapy and combination, respectively, p = 0.60). Changes in nitric oxide (NO) production, vascular cell adhesion molecule-1 (VCAM-1) expression, and reactive oxygen species (ROS) production were similar between the groups. The baseline cholesterol efflux capacity correlated positively with apolipoprotein (apo)A1 and C3, whereas apoA1 and apoC1 showed inverse associations with VCAM-1 expression. The changes in the cholesterol efflux capacity were positively correlated with multiple HDL proteins, especially apoA2.ConclusionsTwo regimens increased the cholesterol efflux capacity of HDL comparably. Multiple HDL proteins, not limited to apoA1, showed a correlation with HDL functions. These results indicate that conventional lipid therapy may have additional effects on HDL functions with changes in HDL proteins.Trial registrationClinicalTrials.gov, number NCT02942602.
Highlights
The influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood
The aim of this study was to compare the effects of two lipid-lowering strategies, atorvastatin 20 mg and atorvastatin 5 mg/ezetimibe 10 mg combination, on HDL functions
The baseline high-density lipoproteincholesterol (HDL-C) levels were marginally higher in the atorvastatin group than they were in the combination group (45 mg/dL and 39 mg/dL, respectively, p = 0.06)
Summary
The influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood. We compared the effect of two lipid-lowering strategies on HDL functions and identified some HDL-related proteins. The role of high-density lipoprotein (HDL) in vascular disease is under active investigation. On the other hand, lowering the low-density lipoprotein-cholesterol (LDL-C) using statins has been the mainstay of pharmacologic therapy aimed at effectively reducing cardiovascular risk [2]. In a recent IMPROVE-IT trial, the application of simvastatin 40 mg/ezetimibe 10 mg combination was shown to reduce cardiovascular risk compared to using simvastatin 40 mg alone [5]. The addition of ezetimibe 10 mg to ongoing statin therapy is highly effective in LDL-C-lowering. Whether the combination of ezetimibe/statin has differential pleiotropic effect, such as modification of HDL function, compared to higher dose statin is not yet completely understood
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