Cardiologie clinique et expérimentale
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Reduced Fetuin A Serum Level is Associated with Faster Stenosis Progression and Increased Valvular Calcification in Elderly Patients with Aortic Stenosis

Dania Mohty, Nancy C?t?, Philippe Pibarot, Dominique Fournier, Andr?e P?pin, Audrey Audet, Jean-Pierre Despr?s and Patrick Mathieu

Background: Fetuin A is a circulating calcium-regulatory glycoprotein that inhibits ectopic and vascular calcification. Aortic stenosis (AS) is a disease process involving an active calcification of the aortic valve (AV). Its prevalence increases markedly with aging. We examined the associations between serum level of Fetuin A with AV calcification, and disease progression rate of AS, in function of age.
Methods: 226 patients operated for AS, were divided into 2 groups according to the median value of age: the younger group (<70 years) and the elderly group (=70 years). Serum fetuin A levels and calcium content of AV were determined respectively by Elisa method and 0-cresolphtalein complexone method. The annualized progression rate of AS was calculated for the subset of patients (n=113) in whom at least 2 transthoracic Doppler-echocardiographic exams separated by at least 6 months were available pre-operatively.
Results: There was no correlation between fetuin A level and AV calcium content or AS progression rate in the subset of younger patients. On the other hand, in the elderly group, the preoperative progression rate of the peak transvalvular gradient was 2-fold faster in patients with serum fetuin A level <0.36 g/L (median value) when compared to those with higher level of fetuin A (9±1 mmHg/year vs. 5±1 mmHg/year, p=0.02). Moreover, there was a negative correlation between calcium content of the AV explanted at the time of surgery and fetuin A serum level (r=-0.22, p=0.05). After adjusting for age, male gender, triglycerides and the morphology of the AV (bicuspid vs. tricuspid), fetuin A remained significantly and inversely associated with AV calcification (r²0.09, β=-67.5, p== 0.04) and AS progression rate (r²=0.30, β=-10.4, p=0.02).
Conclusion: In the elderly patients, reduced level of Fetuin A is associated with enhanced valvular calcification and faster stenosis progression rate. These findings also support that the determinants and mechanisms of the progression of AS may be different in younger patients.