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Lipid-Modulating Treatments for Mixed Dyslipidemia Increase HDL-Associated Phospholipase A2 Activity with Differential Effects on HDL Subfractions

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Lipids

Abstract

The effect of lipid-modulating treatments on modification of high density lipoprotein (HDL) subfractions remains unknown. In this study, mixed dyslipidemia patients (n = 100) inadequately controlled with a standard statin dose were randomized to switch to 40 mg of rosuvastatin or add-on extended release nicotinic acid/laropiprant (ER-NA/LRPT) or add-on fenofibrate. The cholesterol concentrations of HDL (HDL-C) subfractions and HDL-associated lipoprotein-associated phospholipase A2 (HDL-Lp-PLA2) activity were assessed at baseline and 3 months later. We observed that large HDL-C increased by 50 and 6 % in the add-on-ER-NA/LRPT and rosuvastatin groups, respectively, while it decreased by 20 % in the add-on-fenofibrate group (p < 0.01 vs baseline for all groups and p < 0.01 for all comparisons among groups). On the other hand, small HDL-C decreased by 17 % in the add-on-ER-NA/LRPT group (p < 0.01 vs baseline), while it increased by 25 % in the add-on-fenofibrate group (p < 0.01 vs baseline) without any change in the rosuvastatin group (p < 0.01 for all comparisons among groups). HDL-Lp-PLA2 activity increased by 55, 33 and 18 % in add-on-ER-NA/LRPT, add-on-fenofibrate and rosuvastatin groups, respectively (p < 0.01 for all comparisons vs baseline and for all comparisons among groups). In conclusion, add-on-ER-NA/LRPT was associated with an increase in large HDL-C and a decrease in small HDL-C, while opposite effects were noticed in the add-on-fenofibrate group. Add-on-ER-NA/LRPT was associated with the most pronounced increase in HDL-Lp-PLA2 activity.

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Abbreviations

ANCOVA:

Analysis of covariance

CETP:

Cholesterol ester transfer protein

CVD:

Cardiovascular disease

ER-NA/LRPT:

Extended release nicotinic acid/laropiprant

HDL-C:

High density lipoprotein cholesterol

HDL-Lp-PLA2 :

HDL-associated lipoprotein-associated phospholipase A2

HL:

Hepatic lipase

LDL-C:

Low density lipoprotein cholesterol

NCEP-ATP:

National Cholesterol Education Program Adult Treatment Panel

NMR:

Nuclear magnetic resonance

PAF:

Platelet activating factor

PROBE study:

Prospective, randomized, open-label, blinded end point study

SD:

Standard deviation

SPSS:

Statistical Package for the Social Sciences

TAG:

Triacylglycerol(s)

VAP:

Vertical auto profile

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Acknowledgments

The authors would like to thank the Atherothrombosis Research Centre of the University of Ioannina for providing access to the laboratory equipment and facilities.

Conflict of interest

Some of the authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies, including Astra-Zeneca, Abbott and Merck Sharpe and Dohme (MSD). There are no other conflicts of interest to be declared.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Ioannina Medical School, 45 110, Ioannina, Greece

    Anastazia Kei, Evangelos Liberopoulos & Moses Elisaf

  2. Department of Chemistry, Atherothrombosis Research Centre/Laboratory of Biochemistry, University of Ioannina, Ioannina, Greece

    Costantinos Tellis & Alexandros Tselepis

Authors
  1. Anastazia Kei
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  2. Evangelos Liberopoulos
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  3. Costantinos Tellis
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  4. Moses Elisaf
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  5. Alexandros Tselepis
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Correspondence to Evangelos Liberopoulos.

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Kei, A., Liberopoulos, E., Tellis, C. et al. Lipid-Modulating Treatments for Mixed Dyslipidemia Increase HDL-Associated Phospholipase A2 Activity with Differential Effects on HDL Subfractions. Lipids 48, 957–965 (2013). https://doi.org/10.1007/s11745-013-3826-y

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  • DOI: https://doi.org/10.1007/s11745-013-3826-y

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