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

Calvin Yeang, Ming Yow Hung, Young Sup Byun, Paul Clopton, Xiaohong Yang, Joseph L. Witztum, Sotirios Tsimikas

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)594-603
JournalJournal of Clinical Lipidology
Volume10
Issue number3
DOIs
Publication statusPublished - May 1 2016

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Lipoprotein(a)
Apolipoproteins
Therapeutic Uses
Apolipoproteins B
Phospholipids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Fat-Restricted Diet
Niacin
Cardiovascular Diseases
Apolipoprotein B-100
Apoprotein(a)
Lipids
Blood Component Removal
Simvastatin
Therapeutics
Diet

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Nutrition and Dietetics

Cite this

Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a). / Yeang, Calvin; Hung, Ming Yow; Byun, Young Sup; Clopton, Paul; Yang, Xiaohong; Witztum, Joseph L.; Tsimikas, Sotirios.

In: Journal of Clinical Lipidology, Vol. 10, No. 3, 01.05.2016, p. 594-603.

Research output: Contribution to journalArticle

Yeang, Calvin ; Hung, Ming Yow ; Byun, Young Sup ; Clopton, Paul ; Yang, Xiaohong ; Witztum, Joseph L. ; Tsimikas, Sotirios. / Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a). In: Journal of Clinical Lipidology. 2016 ; Vol. 10, No. 3. pp. 594-603.
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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",
author = "Calvin Yeang and Hung, {Ming Yow} and Byun, {Young Sup} and Paul Clopton and Xiaohong Yang and Witztum, {Joseph L.} and Sotirios Tsimikas",
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TY - JOUR

T1 - Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a)

AU - Yeang, Calvin

AU - Hung, Ming Yow

AU - Byun, Young Sup

AU - Clopton, Paul

AU - Yang, Xiaohong

AU - Witztum, Joseph L.

AU - Tsimikas, Sotirios

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Diet

KW - Ezetimibe

KW - Lipoprotein(a)

KW - Niacin

KW - Oxidized phospholipids

KW - Simvastatin

KW - Statin

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