Abstract 6145: Low Fetuin-A Concentrations Predict the Progression of Aortic Valve Calcification in Non-Dialyzed Patients

Abstract

Human fetuin-A (alpha 2 -Heremans Schmid glycoprotein) has been identified as the most potent circulating inhibitor of vascular and soft-tissue calcification. We aimed to investigate the relationship between the serum fetuin-A level and the progression of aortic valve calcification (AVC) assessed by retrospectively ECG-gated Multislice Spiral Computed Tomography (MSCT) in patients with calcific aortic valve disease. A prospective study in 77 non-dialyzed patients (mean age 70 ± 8 years) with echocardiographically proven aortic valve disease was performed. In all patients serum fetuin-A levels were measured by nephelometry (BNII, Dade Behring Holding, Liederbach, Germany) using a polyclonal rabbit anti-human antibody against fetuin-A. For quantification of AVC all patients underwent 16-slice MSCT (Sensation 16, Siemens, Forchheim, Germany with scan parameters as follows: 420ms tube rotation time, 12× 0.75mm collimation, tube voltage 120KV). After a mean follow-up of 12.6 ± 1.4 months a second non-enhanced MSCT examination for quantification of AVC was performed. Images were reconstructed at 60% of the RR interval. AVC was assessed using Agatston AVC score. In multifactorial analysis of covariance including fetuin-A levels, baseline AVC score, the covariables sex, age, body mass index, C-reactive protein, glomerular filtration rate, serum lipids, diabetes, smoking status and hypertension, only fetuin-A levels revealed a significant effect on the progression of AVC (p<0.001). Post-hoc analysis demonstrated that patients with baseline fetuin-A levels lower than the median of the cohort (0.72g/l) showed a significantly higher increase of AVC scores (34.6 ± 31.4%, n=39) than patients with fetuin-A levels larger than the median (10.0 ± 11.2%, p<0.001) despite comparable baseline AVC scores. Vice versa, patients with progressive AVC > 10% (n=48, 62%) had lower fetuin-A serum levels at baseline than non-progressors (n=29, 38%; 0.66±0.13g/L versus 0.82±0.11 g/L, p<0.001). The present study suggests that low fetuin-A serum levels indicating systemic calcification inhibitor deficiency were associated with increased progression of AVC independently of the renal function.