Lipoprotein(a) and apolipoprotein(a) isoform size: Associations with angiographic extent and severity of coronary artery disease, and carotid artery plaque

Atherosclerosis. 2018 Aug:275:232-238. doi: 10.1016/j.atherosclerosis.2018.06.863. Epub 2018 Jun 18.

Abstract

Background and aims: Lipoprotein(a) [Lp(a)] is an emerging genetic risk factor for cardiovascular disease (CVD). We examined whether plasma Lp(a) concentration and apolipoprotein(a) [apo(a)] isoform size are associated with extent and severity of coronary artery disease (CAD), and the presence of carotid artery plaque.

Methods: We included in our study male participants (n = 263) from a cohort with angiographically defined premature CAD (Carotid Ultrasound in Patients with Ischemic Heart Disease). The angiographic extent and severity of CAD were determined by the modified Gensini and Coronary Artery Stenosis≥20% (CAGE) scores. Carotid artery plaque was assessed by bilateral carotid B-mode ultrasound. Apo(a) isoform size was determined by LPA Kringle IV-2 copy number (KIV-2 CN).

Results: Lp(a) concentration, but not KIV-2 CN, was positively associated with the Gensini score. The association remained significant following adjustment for conventional CVD risk factors (all p < 0.05). Lp(a) concentration and elevated Lp(a) [≥50 mg/dL] were positively associated with the CAGE≥20 score, independent of conventional CVD risk factors. KIV-2 C N Q1 (lowest KIV-2 CN quartile) was associated with CAGE≥20 score and KIV-2 CN, with the CAGE≥20 score in those without diabetes. In multivariate models that included phenotypic familial hypercholesterolemia or low-density lipoprotein cholesterol, Lp(a) concentration, but not KIV-2 CN, was independently associated with the Gensini and CAGE≥20 scores. No significant associations between Lp(a) concentration and KIV-2 CN with carotid artery plaque were observed.

Conclusions: Lp(a) concentration, but not apo(a) isoform size, is independently associated with angiographic extent and severity of CAD. Neither Lp(a) nor apo(a) isoform size is associated with carotid artery plaque.

Keywords: Apolipoprotein(a) isoforms; Cardiovascular disease; Kringle IV-2 copy number; Lipoprotein(a); Risk factor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Apoprotein(a) / blood*
  • Australia / epidemiology
  • Biomarkers / blood
  • Carotid Arteries / diagnostic imaging*
  • Carotid Arteries / pathology
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / epidemiology
  • Carotid Artery Diseases / genetics
  • Coronary Angiography*
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / genetics
  • Coronary Stenosis / blood*
  • Coronary Stenosis / diagnostic imaging
  • Coronary Stenosis / epidemiology
  • Coronary Stenosis / genetics
  • Coronary Vessels / diagnostic imaging*
  • Gene Dosage
  • Humans
  • Lipoprotein(a) / blood*
  • Lipoprotein(a) / genetics
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Ultrasonography*

Substances

  • Biomarkers
  • Lipoprotein(a)
  • Apoprotein(a)