Aortic valve calcification in a rat model of aging

Background: Calcification is a bad prognostic factor in heart valve disease. Calcifying aortic valve disease affects over 35% of patients above 75 years of age. In vivo rat models are increasingly used to investigate the underlying pathophysiology. The purpose of this study was to investigate aortic valve calcification in the healthy, aging rat. For this, we used echocardiographic calibrated integrated backscatter (cIB), compared to ex-vivo micro-CT and histology as reference. Methods: A mixed inbred/outbred population of 32 male Lewis/Wistar rats was studied. Group 1 (n=10) of 3 months old rats, group 2 (n=8) 12 months old, group 3 (n=11) 24 months old, and group 4 (n=3) 30 months old. cIB values and blood parameters (creatinine, total cholesterol, calcium, parathyroid hormone (PTH)) were measured. Results: There was a significant increase of cIB values of the aortic valve with age (group 1: 11.3 ± 0.6 dB; group 2: 11.9 ± 0.4 dB; group 3: 13.7 ± 0.5 dB; group 4: 14.8 ± 1.0 dB; P=0.012). This was confirmed by an increase of the calcified volume on ex-vivo micro-CT (P=0.003) and of the histological calcium score (P=0.009). There was no significant difference in total cholesterol and calcium between groups 2-4. There was a significant increase of creatinine and PTH with age (P?0.001). Conclusions: 1. Aortic valve calcification increases with age in the healthy rat. Aging is also associated with renal failure and secondary hyperparathyroidism. 2. This underlines the importance of taking aging into account when studying aortic valve disease. 3. Additionally, it was confirmed that calibrated integrated backscatter is a promising, non-ionising and non-invasive technique for the quantitative echo assessment of aortic valve calcifications in vivo.