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Oxidized phospholipids on apolipoprotein B-100 versus plasminogen and risk of coronary heart disease in the PROCARDIS study

  • Author Footnotes
    1 These authors contributed equally to this work.
    Robert Clarke
    Correspondence
    Corresponding author. Nuffield Department of Population Health, University of Oxford, Big Data Institute Building, Old Road Campus, Oxford, OX3 7LF, United Kingdom.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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  • Imen Hammami
    Affiliations
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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  • Paul Sherliker
    Affiliations
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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  • Elsa Valdes-Marquez
    Affiliations
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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  • Hugh Watkins
    Affiliations
    Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
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  • Michael Hill
    Affiliations
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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  • Xiaohong Yang
    Affiliations
    Division of Cardiovascular Diseases, University of California, San Diego, USA
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Sotirios Tsimikas
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Division of Cardiovascular Diseases, University of California, San Diego, USA
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Jemma C. Hopewell
    Correspondence
    Corresponding author. Nuffield Department of Population Health, University of Oxford, Big Data Institute Building, Old Road Campus, Oxford, OX3 7LF, United Kingdom.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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  • on behalf of thePROCARDIS Consortium
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Plasma levels of oxidized phospholipids carried on apolipoprotein B-100 are predictive of coronary heart disease.
      • Plasma levels of oxidized phospholipids carried on plasminogen and plasminogen were unrelated to risk of coronary heart disease.
      • The effects of oxidized phospholipids on risk of coronary heart disease are chiefly mediated by their carriage on Lp(a).

      Abstract

      Background and aims

      Oxidized phospholipids carried on the apolipoprotein B-100 (OxPL-apoB) component of Lp(a) are predictive of coronary heart disease (CHD), but the role of oxidized phospholipids carried on plasminogen (OxPL-PLG) is unknown. We examined the independent effects of OxPL-apoB and OxPL-PLG for risk of CHD before and after adjustment for Lp(a).

      Methods

      Plasma levels of OxPL-apoB, OxPL-PLG, plasminogen and Lp(a) were measured in the PROCARDIS study of early-onset CHD (906 cases/858 controls). Multivariable logistic regression was used to estimate the odds ratios (OR) for each biomarker with CHD after adjustment for established risk factors.

      Results

      Mean levels of OxPL-apoB were higher in cases than controls, but levels of OxPL-PLG and plasminogen were similar. For OxPL-apoB, individuals in the top vs bottom fifth had 2-fold higher age and sex-adjusted OR of CHD (OR = 2.61 [95%CI: 1.91, 3.55]), which were partially attenuated after adjustment for established risk factors. The findings for OxPL-apoB and CHD in PROCARDIS were comparable with those of a meta-analysis of all such studies. However, the associations of OxPL-apoB with CHD were fully attenuated by additional adjustment for Lp(a) (OR = 0.93 [0.54,1.60]). Neither OxPL-PLG nor plasminogen were associated with CHD. Overall, there were no differences in the predictive value for CHD of high vs normal levels (<20th or >80th percentile) of OxPL-apoB, OxPL-PLG, plasminogen or Lp(a) after stratifying for each other.

      Conclusions

      These results highlight the context-dependency of OxPL in plasma and suggest that their associated risk of CHD is chiefly mediated by their carriage on Lp(a).

      Graphical abstract

      Keywords

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