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J Clin Lipidol. 2016 May-Jun;10(3):594-603. doi: 10.1016/j.jacl.2016.01.005. Epub 2016 Mar 8.

Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a).

Author information

1
Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California, La Jolla, CA, USA.
2
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan.
3
Division of Cardiology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
4
San Diego Veteran's Administration Medical Center, La Jolla, CA, USA.
5
Division of Endocrinology and Metabolism, Department of Medicine, University of California, La Jolla, CA, USA.
6
Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California, La Jolla, CA, USA. Electronic address: stsimikas@ucsd.edu.

Abstract

BACKGROUND:

Oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL-apoB) reflect the biological activity of lipoprotein(a) (Lp[a]) and predict cardiovascular disease events. However, studies with statins and low-fat diets show increases in OxPL-apoB and Lp(a).

OBJECTIVE:

This study evaluated changes in OxPL-apoB and Lp(a) with extended-release niacin (N), ezetimibe/simvastatin (E/S) and combination E/S/N. A systematic literature review of previously published trials, measuring both OxPL-apoB and Lp(a) after therapeutic interventions, was also performed.

METHODS:

OxPL-apoB and Lp(a) were measured in 591 patients at baseline and 24 weeks after therapy with N, E/S, or E/S/N in a previously completed randomized trial of hypercholesterolemic patients. The literature review included 12 trials and 3896 patients evaluating statins, low-fat diets, antisense to apolipoprotein(a) and lipid apheresis.

RESULTS:

Niacin decreased OxPL-apoB levels (median [interquartile range]; 3.5 [2.2-9.2] nM to 3.1 [1.8-7.2] nM, P < .01) and Lp(a) (10.9 [4.6-38.4] to 9.3 [3.1-32.9] mg/dL, P < .01). In contrast, E/S and E/S/N significantly increased OxPL-apoB (3.5 [2.1-7.8] to 4.9 [3.0-11.1] nM, P < .01) and (3.3 [1.9-9.3] to 4.3 [2.6-11.2] nM, P < .01), respectively and Lp(a) (11.5 [6.1-36.4] to 14.9 [6.6-54.6] mg/dL, P < .01) and (11.3 [5.4-43.8] to 11.6 [5.9-52.8] mg/dL, P < .01), respectively. The systematic review of statins and diet demonstrated 23.8% and 21.3% mean increases in OxPL-apoB and 10.6% and 19.4% increases in Lp(a), respectively. However 44.1% and 52.0% decreases in OxPL-apoB and Lp(a), respectively, were present with Lp(a)-lowering therapies.

CONCLUSIONS:

This study demonstrates differential changes in OxPL-apoB and Lp(a) with various lipid-lowering approaches. These changes in OxPL-apoB and Lp(a) may provide insights into the results and interpretation of recent cardiovascular disease outcomes trials.

KEYWORDS:

Diet; Ezetimibe; Lipoprotein(a); Niacin; Oxidized phospholipids; Simvastatin; Statin

PMID:
27206947
DOI:
10.1016/j.jacl.2016.01.005
[Indexed for MEDLINE]

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