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Oxidized Phospholipids and Calcific Aortic Valvular Disease.

Harpreet S Bhatia1, Marc R Dweck2, Neil Craig2

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Oxidized phospholipids (OxPL-apoB) predict calcific aortic valve disease (CAVD) presence, incidence, and progression, especially with high lipoprotein(a) [Lp(a)] levels. This highlights OxPL-apoB as a potential therapeutic target for CAVD.

Keywords:
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Area of Science:

  • Cardiovascular Research
  • Atherosclerosis and Vascular Biology
  • Biomarkers in Heart Disease

Background:

  • Oxidized phospholipids (OxPLs) carried by apolipoprotein B-100 (OxPL-apoB) and lipoprotein(a) [Lp(a)] are implicated in calcific aortic valve disease (CAVD).
  • Both OxPL-apoB and Lp(a) have been independently associated with CAVD, suggesting a potential role in its pathogenesis.

Purpose of the Study:

  • To investigate the associations between OxPL-apoB, Lp(a), and the prevalence, incidence, and progression of CAVD.
  • To elucidate the combined and independent roles of OxPL-apoB and Lp(a) in the development and advancement of aortic valve calcification and stenosis.

Main Methods:

  • Utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA) and a meta-analysis of 4 randomized trials involving participants with established aortic stenosis (AS).
  • Assessed OxPL-apoB and Lp(a) levels and their correlation with aortic valve calcium (AVC) at baseline and over 9.5 years using multivariable regression models.
  • Evaluated the association of OxPL-apoB and Lp(a) with AS progression, measured by the annualized change in peak aortic valve jet velocity.

Main Results:

  • In MESA, both OxPL-apoB and Lp(a) were linked to prevalent AVC, with a significant interaction observed between them.
  • Both markers were associated with incident AVC, and their interaction indicated higher odds of prevalent and incident AVC with increasing Lp(a) levels.
  • In the meta-analysis, while both markers individually predicted faster AS progression, only OxPL-apoB remained a significant predictor when analyzed together.

Conclusions:

  • OxPL-apoB is a significant predictor of AVC presence, incidence, and AS progression, particularly when Lp(a) levels are elevated.
  • The findings suggest a synergistic effect between OxPL-apoB and Lp(a) in the pathogenesis of CAVD.
  • OxPL-apoB emerges as a potential novel therapeutic target for managing and preventing CAVD.