oa Angiotensin Receptor Blocker Has no Effect on Atherosclerotic Factors in AVS

Aortic valve sclerosis (AVS) is a chronic progressive disease affecting 25% of the population over the age of 65. Despite this high prevalence, there are currently no preventative therapies which inhibit the progression of AVS. This study sought to determine the effects of an angiotensin II type 1 receptor blocker (ARB), alone or in combination with a statin, on AVS. Male New Zealand White rabbits were fed either regular chow (Control, n=5) or an atherogenic diet for a period of 18 months to induce AVS. Recognizing the clinical reality, therapy was introduced after disease onset. After 12 months, rabbits were block randomly assigned to four groups receiving either no treatment (Cholesterol, n=6), olmesartan medoxomil (Olmesartan, n=7), atorvastatin calcium (Atorvastatin, n=7), or a combination of both drugs (Combination, n=7) for the final 6 months. Magnetic resonance imaging (MRI) was used to monitor disease progress throughout the treatment period. After sacrifice, valve lesions were analyzed using histology and immunohistochemistry. In vivo disease monitoring yielded no discernible treatment effect. While Cholesterol cusps were significantly thicker than Control throughout the treatment period (0.465 ± 0.030 vs 0.388 ± 0.023mm for Cholesterol and Control, respectively, at 18 months), the various treatments had no positive effect on cusp thickness, and were all identical to Cholesterol at 18 months. Aortic valve area provided similar results; while significant disease was established (0.379 ± 0.033 vs 0.623 ± 0.074cm2 for Cholesterol and Control, respectively, at 18 months), there were no significant differences between treatment groups. Histological analysis of Cholesterol, Atorvastatin, Olmesartan, and Combination cusps revealed fibrosal thickening, lipid deposition, macrophage infiltration, and minor calcification. However, morphological analysis did not reveal significant differences in lesion composition among the treatment groups. Treatment efficacy was confirmed by analysis of aortic lesion area which revealed a significant reduction of atherosclerosis in Olmesartan-treated animals. Neither olmesartan medoxomil nor atorvastatin calcium, alone or in combination, provide demonstrable benefit in the treatment of established AVS despite success in the treatment of atherosclerosis.