Effect of two lipid-lowering strategies on high-density lipoprotein function and some HDL-related proteins: a randomized clinical trial

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0433-6) contains supplementary material, which is available to authorized users.

Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model

“…As per the impact of statins on HDL CEC, some studies evidenced benefits after 6–10 weeks of statin treatment [ 28 , 29 , 30 ], whereas others did not [ 31 , 32 ]. Although we observed no changes in cholesterol levels within our studied timeframe, the potential mechanisms by which longer statin treatment periods may interfere with HDL cholesterol removal remain to be investigated, mostly considering no changes in APOA-I content, as discussed below.…”

High density lipoprotein functionality and cardiovascular events and mortality: A systematic review and meta-analysis

“…Presence of apolipoproteinA-II in HDL has been reported to increase cholesterol efflux from macrophages [50]. Moreover, the higher proportion of participants on statin treatment in the CAD group might have had a positive impact on the HDL functions, including cholesterol efflux capacity [51]. We hypothesized that further adjustment of multivariate models would be desirable and might have an impact on the direction of results.…”

Ezetimibe Monotherapy Reduces Serum Levels of Platelet-Activating Factor Acetylhydrolase in Patients With Dyslipidemia

“…In this study, ezetimibe monotherapy was expected to improve HDL-CEC, since previous reports demonstrated that ezetimibe affects reverse cholesterol transport [19, 20]. On the other hand, it was reported that treatment with a combination of atorvastatin plus ezetimibe did not increase HDL-CEC [21, 22]. Ezetimibe monotherapy did not improve HDL-CEC in this study.…”