Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study

Seung Hyuk Choi; Andrew Chae; Elizabeth Miller; Michael Messig; Fady Ntanios; Anthony N. DeMaria; Steven E. Nissen; Joseph L. Witztum; Sotirios Tsimikas

doi:10.1016/j.jacc.2008.02.066

Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study

Seung Hyuk Choi, Andrew Chae, Elizabeth Miller, Michael Messig, Fady Ntanios, Anthony N. DeMaria, Steven E. Nissen, Joseph L. Witztum, Sotirios Tsimikas

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Abstract

Objectives: This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume. Background: Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known. Methods: In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed. Results: There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume. Conclusions: Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.

Original language	English (US)
Pages (from-to)	24-32
Number of pages	9
Journal	Journal of the American College of Cardiology
Volume	52
Issue number	1
DOIs	https://doi.org/10.1016/j.jacc.2008.02.066
State	Published - Jul 1 2008

Bibliographical note

Funding Information:
Drs. Tsimikas and Witztum are named as inventors of patents related to antibodies to oxidized low-density lipoprotein owned by the University of California. Supported by an investigator-initiated grant from Pfizer Inc and from the Fondation Leducq. Assistance in developing the figures, but not content development support, was provided by Envision Pharma and was funded by Pfizer Inc. Drs. Messig and Ntanios are employees of Pfizer Inc. Peter Libby, MD, served as Guest Editor for this article.

Keywords

atherosclerosis
lipoprotein (a)
lipoproteins
oxidation
oxidized phospholipids

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Choi, S. H., Chae, A., Miller, E., Messig, M., Ntanios, F., DeMaria, A. N., Nissen, S. E., Witztum, J. L., & Tsimikas, S. (2008). Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study. Journal of the American College of Cardiology, 52(1), 24-32. https://doi.org/10.1016/j.jacc.2008.02.066

Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study. / Choi, Seung Hyuk; Chae, Andrew; Miller, Elizabeth; Messig, Michael; Ntanios, Fady; DeMaria, Anthony N.; Nissen, Steven E.; Witztum, Joseph L.; Tsimikas, Sotirios.

In: Journal of the American College of Cardiology, Vol. 52, No. 1, 01.07.2008, p. 24-32.

Research output: Contribution to journal › Article › peer-review

Choi, SH, Chae, A, Miller, E, Messig, M, Ntanios, F, DeMaria, AN, Nissen, SE, Witztum, JL & Tsimikas, S 2008, 'Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study', Journal of the American College of Cardiology, vol. 52, no. 1, pp. 24-32. https://doi.org/10.1016/j.jacc.2008.02.066

Choi SH, Chae A, Miller E, Messig M, Ntanios F, DeMaria AN et al. Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study. Journal of the American College of Cardiology. 2008 Jul 1;52(1):24-32. https://doi.org/10.1016/j.jacc.2008.02.066

Choi, Seung Hyuk ; Chae, Andrew ; Miller, Elizabeth ; Messig, Michael ; Ntanios, Fady ; DeMaria, Anthony N. ; Nissen, Steven E. ; Witztum, Joseph L. ; Tsimikas, Sotirios. / Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study. In: Journal of the American College of Cardiology. 2008 ; Vol. 52, No. 1. pp. 24-32.

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title = "Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study",

abstract = "Objectives: This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume. Background: Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known. Methods: In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed. Results: There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume. Conclusions: Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.",

keywords = "atherosclerosis, lipoprotein (a), lipoproteins, oxidation, oxidized phospholipids",

author = "Choi, {Seung Hyuk} and Andrew Chae and Elizabeth Miller and Michael Messig and Fady Ntanios and DeMaria, {Anthony N.} and Nissen, {Steven E.} and Witztum, {Joseph L.} and Sotirios Tsimikas",

note = "Funding Information: Drs. Tsimikas and Witztum are named as inventors of patents related to antibodies to oxidized low-density lipoprotein owned by the University of California. Supported by an investigator-initiated grant from Pfizer Inc and from the Fondation Leducq. Assistance in developing the figures, but not content development support, was provided by Envision Pharma and was funded by Pfizer Inc. Drs. Messig and Ntanios are employees of Pfizer Inc. Peter Libby, MD, served as Guest Editor for this article. ",

year = "2008",

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day = "1",

doi = "10.1016/j.jacc.2008.02.066",

language = "English (US)",

volume = "52",

pages = "24--32",

journal = "Journal of the American College of Cardiology.",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "1",

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TY - JOUR

T1 - Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study

AU - Choi, Seung Hyuk

AU - Chae, Andrew

AU - Miller, Elizabeth

AU - Messig, Michael

AU - Ntanios, Fady

AU - DeMaria, Anthony N.

AU - Nissen, Steven E.

AU - Witztum, Joseph L.

AU - Tsimikas, Sotirios

N1 - Funding Information: Drs. Tsimikas and Witztum are named as inventors of patents related to antibodies to oxidized low-density lipoprotein owned by the University of California. Supported by an investigator-initiated grant from Pfizer Inc and from the Fondation Leducq. Assistance in developing the figures, but not content development support, was provided by Envision Pharma and was funded by Pfizer Inc. Drs. Messig and Ntanios are employees of Pfizer Inc. Peter Libby, MD, served as Guest Editor for this article.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Objectives: This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume. Background: Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known. Methods: In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed. Results: There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume. Conclusions: Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.

AB - Objectives: This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume. Background: Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known. Methods: In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed. Results: There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume. Conclusions: Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.

KW - atherosclerosis

KW - lipoprotein (a)

KW - lipoproteins

KW - oxidation

KW - oxidized phospholipids

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Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume. Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study

Abstract

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