Lipoprotein(a), Oxidized Phospholipids, and Coronary Artery Disease Severity and Outcomes

J Am Coll Cardiol. 2023 May 9;81(18):1780-1792. doi: 10.1016/j.jacc.2023.02.050.

Abstract

Background: Lipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPLs) are each independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs predict coronary artery disease (CAD) severity and outcomes in a contemporary, statin-treated cohort is not well established.

Objectives: This study sought to evaluate the relationships between Lp(a) particle concentration and OxPLs associated with apolipoprotein B (OxPL-apoB) or apolipoprotein(a) (OxPL-apo[a]) with angiographic CAD and cardiovascular outcomes.

Methods: Among 1,098 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study, Lp(a), OxPL-apoB, and OxPL-apo(a) were measured. Logistic regression estimated the risk of multivessel coronary stenoses by Lp(a)-related biomarker level. Cox proportional hazards regression estimated the risk of major adverse cardiovascular events (MACEs) (coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) in follow-up.

Results: Median Lp(a) was 26.45 nmol/L (IQR: 11.39-89.49 nmol/L). Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R ≥0.91 for all pairwise combinations). Lp(a) and OxPL-apoB were associated with multivessel CAD. Odds of multivessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI: 1.03-1.18; P = 0.006), 1.18 (95% CI: 1.03-1.34; P = 0.01), and 1.07 (95% CI: 0.99-1.16; P = 0.07), respectively. All biomarkers were associated with cardiovascular events. HRs for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI: 1.03-1.14; P = 0.001), 1.15 (95% CI: 1.05-1.26; P = 0.004), and 1.07 (95% CI: 1.01-1.14; P = 0.02), respectively.

Conclusions: In patients undergoing coronary angiography, Lp(a) and OxPL-apoB are associated with multivessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident cardiovascular events. (Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868).

Keywords: atherosclerosis; coronary artery disease; lipids and lipoproteins; lipoprotein(a).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins A
  • Apolipoproteins B
  • Apoprotein(a)
  • Biomarkers
  • Cardiovascular Diseases*
  • Coronary Artery Disease* / diagnostic imaging
  • Humans
  • Lipoprotein(a)
  • Oxidation-Reduction
  • Phospholipids

Substances

  • Lipoprotein(a)
  • Phospholipids
  • Apolipoproteins B
  • Apolipoproteins A
  • Biomarkers
  • Apoprotein(a)

Associated data

  • ClinicalTrials.gov/NCT00842868