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

Atherosclerosis. 2022 Aug:354:15-22. doi: 10.1016/j.atherosclerosis.2022.06.1020. Epub 2022 Jun 25.

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).

Keywords: Lipoprotein(a) and coronary heart disease; Oxidized phospholipids; Plasminogen.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein B-100
  • Apolipoproteins B
  • Coronary Disease* / diagnosis
  • Coronary Disease* / epidemiology
  • Humans
  • Lipoprotein(a)
  • Oxidation-Reduction
  • Phospholipids*
  • Plasminogen

Substances

  • Apolipoprotein B-100
  • Apolipoproteins B
  • Lipoprotein(a)
  • Phospholipids
  • Plasminogen