The relationship between endothelial function and aortic valve calcification: Multi-Ethnic Study of Atherosclerosis

Atherosclerosis. 2019 Jan:280:155-165. doi: 10.1016/j.atherosclerosis.2018.11.029. Epub 2018 Nov 28.

Abstract

Background and aims: Aortic valve calcification (AVC) may be associated with atherogenic processes arising from endothelial dysfunction (ED). Limited data is available about the relationship between ED, defined by flow mediated dilation (FMD%) and biomarkers, and the prevalence and progression of AVC in a multiethnic population.

Methods: A sample of 3475 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with both initial and repeat CT scans at a mean of 2.65 ± 0.84 years and FMD% and serologic markers of ED [ C-reactive protein (CRP), Von Willebrand factor (vWF), Plasminogen Activator Inhibitor (PAI), fibrinogen, Interleukin 6 (IL6), E-selectin and ICAM-1 (Intercellular Adhesion Molecule 1)], were analyzed. Multivariate modeling evaluated the association between ED and the prevalent AVC and AVC progression.

Results: The median levels of FMD% was lower and vWF%, fibrinogen, IL6 and ICAM-1 were significantly higher in the AVC prevalence group versus no AVC prevalence (all p < 0.001). In the fully adjusted model for established risk factors, decreasing FMD% or increasing biomarkers was not independently associated with AVC prevalence [OR FMD% 1.028 (0.786, 1.346), CRP 0.981 (0.825, 1.168), vWF 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 1.116 (0.424, 2.940), IL6 1.065 (0.779, 1.456), E-selectin 0.876 (0.479, 1.602) and ICAM-1 1.766 (0.834, 3.743)]. In the AVC progression group, FMD%, vWF%, fibrinogen and IL6 were significantly different (p < 0.05). After adjusting for cardiac risk factors, AVC progression was not independently associated with decreasing FMD% or increasing biomarkers [OR FMD% 1.105 (0.835, 1.463), CRP 1.014 (0.849, 1.210), vWF% 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 0.909 (0.338, 2.443), IL6 1.061 (0.772, 1.459), E-selectin 0.794 (0.426, 1.480) and ICAM-1 0.998 (0.476, 2.092)].

Conclusions: Endothelial dysfunction by FMD% and biomarkers is not significantly associated with the prevalence or progression of aortic valve calcification after adjustment for cardiac risk factors.

Keywords: Aortic valve calcification; Biomarkers; Endothelial dysfunction; FMD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Valve / pathology*
  • Aortic Valve / physiopathology
  • Aortic Valve Stenosis / complications
  • Aortic Valve Stenosis / ethnology
  • Aortic Valve Stenosis / physiopathology*
  • Atherosclerosis / complications
  • Atherosclerosis / ethnology
  • Atherosclerosis / physiopathology*
  • Biomarkers / analysis
  • C-Reactive Protein / analysis
  • Calcinosis / complications
  • Calcinosis / ethnology
  • Calcinosis / physiopathology*
  • Disease Progression
  • E-Selectin / analysis
  • Endothelium, Vascular / physiopathology
  • Ethnicity
  • Female
  • Fibrinogen / analysis
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prevalence
  • Prospective Studies
  • Risk Factors

Substances

  • Biomarkers
  • E-Selectin
  • ICAM1 protein, human
  • SELE protein, human
  • Intercellular Adhesion Molecule-1
  • Fibrinogen
  • C-Reactive Protein

Supplementary concepts

  • Aortic Valve, Calcification of