Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events

Anand Prasad, Paul Clopton, Colby Ayers, Amit Khera, James A de Lemos, Joseph L. Witztum, Sotirios Tsimikas

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective-Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. Approach and Results-IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10.5-year follow-up. Coronary artery calcium score, abdominal aortic plaque by magnetic resonance imaging, and MACE were quantified. IgG MDA-LDL and IgG and IgM apolipoprotein B-100-immune complexes were significantly different between groups, with blacks having the highest levels of IgG MDA-LDL and IgG apolipoprotein B-100-immune complexes and Hispanics having the highest levels of IgM apolipoprotein B-100-immune complexes (P<0.001 for all). IgGs tended to be higher and IgMs lower with age for all markers. In multivariable-adjusted binary logistic regression analysis, a doubling of IgG MDA-LDL levels was associated with prevalent coronary artery calcium score >10 Agatston units (odds ratio [95% confidence interval], 1.21 [1.07-1.36]; P=0.002). Multivariable-adjusted Cox regression analysis revealed that IgG MDA-LDL was independently associated with time to incident MACE in the entire group (hazard ratio [95% confidence interval], 1.76 [1.16-2.72]; P=0.009 for fourth versus first quartile). This effect was particularly prominent in black subjects (hazard ratio [95% confidence interval], 2.52 [1.39-4.57]; P=0.002). Conclusions-Autoantibodies to oxidized lipoproteins and immune complexes with apoB-100 lipoproteins vary significantly by sex, age, and ethnicity. Higher baseline IgG MDA-LDL titers independently associate with new MACE. These findings may contribute to the understanding of differences in ethnic-specific MACE events.

Original languageEnglish (US)
Pages (from-to)1213-1221
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume37
Issue number6
DOIs
StatePublished - Jun 1 2017

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Apolipoproteins B
Antigen-Antibody Complex
Malondialdehyde
LDL Lipoproteins
Apolipoprotein B-100
Autoantibodies
Atherosclerosis
Immunoglobulin G
Lipoproteins
Immunoglobulin M
Confidence Intervals
Hispanic Americans
Adaptive Immunity
Ethnic Groups
Innate Immunity
Coronary Vessels
Odds Ratio
Regression Analysis
Magnetic Resonance Imaging
Calcium

Keywords

  • autoantibodies
  • biomarkers
  • cardiovascular diseases
  • immunity, innate
  • lipids

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events. / Prasad, Anand; Clopton, Paul; Ayers, Colby; Khera, Amit; de Lemos, James A; Witztum, Joseph L.; Tsimikas, Sotirios.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 37, No. 6, 01.06.2017, p. 1213-1221.

Research output: Contribution to journalArticle

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abstract = "Objective-Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. Approach and Results-IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10.5-year follow-up. Coronary artery calcium score, abdominal aortic plaque by magnetic resonance imaging, and MACE were quantified. IgG MDA-LDL and IgG and IgM apolipoprotein B-100-immune complexes were significantly different between groups, with blacks having the highest levels of IgG MDA-LDL and IgG apolipoprotein B-100-immune complexes and Hispanics having the highest levels of IgM apolipoprotein B-100-immune complexes (P<0.001 for all). IgGs tended to be higher and IgMs lower with age for all markers. In multivariable-adjusted binary logistic regression analysis, a doubling of IgG MDA-LDL levels was associated with prevalent coronary artery calcium score >10 Agatston units (odds ratio [95{\%} confidence interval], 1.21 [1.07-1.36]; P=0.002). Multivariable-adjusted Cox regression analysis revealed that IgG MDA-LDL was independently associated with time to incident MACE in the entire group (hazard ratio [95{\%} confidence interval], 1.76 [1.16-2.72]; P=0.009 for fourth versus first quartile). This effect was particularly prominent in black subjects (hazard ratio [95{\%} confidence interval], 2.52 [1.39-4.57]; P=0.002). Conclusions-Autoantibodies to oxidized lipoproteins and immune complexes with apoB-100 lipoproteins vary significantly by sex, age, and ethnicity. Higher baseline IgG MDA-LDL titers independently associate with new MACE. These findings may contribute to the understanding of differences in ethnic-specific MACE events.",
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AU - Clopton, Paul

AU - Ayers, Colby

AU - Khera, Amit

AU - de Lemos, James A

AU - Witztum, Joseph L.

AU - Tsimikas, Sotirios

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N2 - Objective-Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. Approach and Results-IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10.5-year follow-up. Coronary artery calcium score, abdominal aortic plaque by magnetic resonance imaging, and MACE were quantified. IgG MDA-LDL and IgG and IgM apolipoprotein B-100-immune complexes were significantly different between groups, with blacks having the highest levels of IgG MDA-LDL and IgG apolipoprotein B-100-immune complexes and Hispanics having the highest levels of IgM apolipoprotein B-100-immune complexes (P<0.001 for all). IgGs tended to be higher and IgMs lower with age for all markers. In multivariable-adjusted binary logistic regression analysis, a doubling of IgG MDA-LDL levels was associated with prevalent coronary artery calcium score >10 Agatston units (odds ratio [95% confidence interval], 1.21 [1.07-1.36]; P=0.002). Multivariable-adjusted Cox regression analysis revealed that IgG MDA-LDL was independently associated with time to incident MACE in the entire group (hazard ratio [95% confidence interval], 1.76 [1.16-2.72]; P=0.009 for fourth versus first quartile). This effect was particularly prominent in black subjects (hazard ratio [95% confidence interval], 2.52 [1.39-4.57]; P=0.002). Conclusions-Autoantibodies to oxidized lipoproteins and immune complexes with apoB-100 lipoproteins vary significantly by sex, age, and ethnicity. Higher baseline IgG MDA-LDL titers independently associate with new MACE. These findings may contribute to the understanding of differences in ethnic-specific MACE events.

AB - Objective-Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. Approach and Results-IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10.5-year follow-up. Coronary artery calcium score, abdominal aortic plaque by magnetic resonance imaging, and MACE were quantified. IgG MDA-LDL and IgG and IgM apolipoprotein B-100-immune complexes were significantly different between groups, with blacks having the highest levels of IgG MDA-LDL and IgG apolipoprotein B-100-immune complexes and Hispanics having the highest levels of IgM apolipoprotein B-100-immune complexes (P<0.001 for all). IgGs tended to be higher and IgMs lower with age for all markers. In multivariable-adjusted binary logistic regression analysis, a doubling of IgG MDA-LDL levels was associated with prevalent coronary artery calcium score >10 Agatston units (odds ratio [95% confidence interval], 1.21 [1.07-1.36]; P=0.002). Multivariable-adjusted Cox regression analysis revealed that IgG MDA-LDL was independently associated with time to incident MACE in the entire group (hazard ratio [95% confidence interval], 1.76 [1.16-2.72]; P=0.009 for fourth versus first quartile). This effect was particularly prominent in black subjects (hazard ratio [95% confidence interval], 2.52 [1.39-4.57]; P=0.002). Conclusions-Autoantibodies to oxidized lipoproteins and immune complexes with apoB-100 lipoproteins vary significantly by sex, age, and ethnicity. Higher baseline IgG MDA-LDL titers independently associate with new MACE. These findings may contribute to the understanding of differences in ethnic-specific MACE events.

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KW - biomarkers

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