Introduction: Aortic stenosis (AS) is the most common valvular heart disease in westernised 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 Å) 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.
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Dr Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research, Ottawa, Ontario, Canada. Dr Després is the scientific director of the International Chair on Cardiometabolic Risk at University Laval, which is supported by an unrestricted grant from Sanofi-Aventis. Dr Mohty is supported by a postdoctoral fellow scholarship from the training program in obesity, Canadian Institutes of Health Research, Ottawa, Canada. Dr Mathieu is a research scholar from the Fonds de Recherches en Santé du Québec, Montréal, Canada.
Funding: This work was supported by grants from the Canadian Institute of Health Research (CIHR), Ottawa, Canada, grant number MOP 79342, the Heart and Stroke Foundation of Québec, Montréal, Canada, the Quebec Heart Institute Foundation, Québec, Canada, and the Réseau d’Échange de Tissus et Échantillons Biologiques, Fonds de Recherche en Santé du Québec, Montréal, Canada.
Competing interests: None.