Soluble LR11 associates with aortic root calcification in asymptomatic treated male patients with familial hypercholesterolemia

Atherosclerosis. 2017 Oct:265:299-304. doi: 10.1016/j.atherosclerosis.2017.06.018. Epub 2017 Jun 9.

Abstract

Background and aims: Despite statin treatment, a high prevalence of severe vascular calcification is found in patients with familial hypercholesterolemia (FH). We assessed the relation between the circulating soluble form of low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11), a risk factor for cardiovascular disease, and vascular calcification in asymptomatic statin-treated heterozygous FH patients.

Methods: In 123 asymptomatic heterozygous FH patients (age 40-69 years), aortic root (ARC), aortic valve (AVC) and coronary artery calcification (CAC) were determined with CT-based calcium scoring expressed in Agatston units. Plasma sLR11 levels were measured by sandwich ELISA.

Results: Seventy-three patients displayed ARC, 48 had AVC and 96 CAC. Plasma sLR11 levels were positively correlated with the presence of ARC (r = 0.2, p = 0.03), but not with AVC or CAC. The correlation between sLR11 levels and ARC was restricted to male FH patients (r = 0.31, p = 0.006). Multivariate logistic analyses showed that the association of plasma sLR11 with the presence of ARC was independent of other determinants (Adjusted Odds Ratio, 2.01 (95% CI = 1.28-3.16) p = 0.002).

Conclusions: Plasma sLR11 is associated with ARC in male FH patients and may be mechanistically involved in the differential distribution of atherosclerotic lesions in the vasculature.

Keywords: Aortic root; Familial hypercholesterolemia; Plasma sLR11; Vascular calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aortic Diseases / blood*
  • Aortic Diseases / etiology*
  • Aortic Valve*
  • Asymptomatic Diseases
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / etiology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type II / complications*
  • Hyperlipoproteinemia Type II / drug therapy
  • LDL-Receptor Related Proteins / blood*
  • Male
  • Membrane Transport Proteins / blood*
  • Middle Aged
  • Vascular Calcification / blood*
  • Vascular Calcification / etiology*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • LDL-Receptor Related Proteins
  • Membrane Transport Proteins
  • SORL1 protein, human