Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis

Heart. 2008 Sep;94(9):1175-80. doi: 10.1136/hrt.2007.125740. Epub 2007 Oct 11.

Abstract

Introduction: Aortic stenosis (AS) is the most common valvular heart disease in westernized societies. AS is a disease process akin to atherosclerosis in which calcification and tissue remodelling play a crucial role. In patients with moderate/severe AS, we sought to determine whether the remodelling process would be in relationship with transvalvular gradients and circulating oxidised low-density lipoprotein (ox-LDL) levels.

Methods: In 105 patients with AS, the aortic valve and blood plasma were collected at the time of valve replacement surgery. The degree of valve tissue remodelling was assessed using a scoring system (Score: 1-4) and the amount of calcium within the valve cusps was determined. The standard plasma lipid profile, the size of LDL particles and the plasma level of circulating ox-LDL (4E6 antibody) were determined.

Results: After adjustment for covariables, aortic remodelling score was significantly related to transvalvular gradients measured by Doppler echocardiography before surgery. Patients with higher valve remodelling score had higher circulating ox-LDL levels (score 2: 27.3 (SEM 2.6) U/l; score 3: 32.2 (SEM 2.3) U/l; score 4: 38.3 (SEM 2.3) U/l; p = 0.02). After correction for age, gender, hypertension and HDL-C, the plasma level of ox-LDL remained significantly associated with the aortic valve remodelling score (p<0.001). The plasma level of ox-LDL was significantly associated with LDL-C (r = 0.41; p<0.001), apoB (r = 0.59; p<0.001), triglyceride (r = 0.39; p<0.001), Apo A-I (r = 0.23; p = 0.01) and cholesterol in small (<255 A) LDL particles (r = 0.22; p = 0.02). After correction for covariables, circulating ox-LDL levels remained significantly associated with apoB (p<0.001) and triglyceride (p = 0.01) levels.

Conclusion: Increased level of circulating ox-LDL is associated with worse fibrocalcific remodelling of valvular tissue in AS. It remains to be determined whether circulating ox-LDL is a risk marker for a highly atherogenic profile and/or a circulating molecule which is actively involved in the pathogenesis of calcific aortic valve disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / blood*
  • Aortic Valve Stenosis / etiology
  • Aortic Valve Stenosis / pathology
  • Apolipoproteins B / blood
  • Biomarkers / blood
  • Calcinosis / blood*
  • Calcinosis / complications
  • Calcinosis / pathology
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Echocardiography, Doppler
  • Female
  • Humans
  • Linear Models
  • Lipoproteins, LDL / blood*
  • Male
  • Statistics, Nonparametric
  • Triglycerides / blood

Substances

  • Apolipoproteins B
  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipoproteins, LDL
  • Triglycerides
  • oxidized low density lipoprotein