The Influence of Statins on Levels of Calcification Biomarkers in Patients with Aortic Sclerosis or Mild Aortic Stenosis

Background and aim of the study: Following the SEAS and SALTIRE studies in moderate-to-severe aortic stenosis (AS), it was postulated that the statin treatment had been initiated far too late during the disease course. Thus, the study aim was to assess the effect of four-week atorvastatin treatment (20 mg/day) on levels of calcification biomarkers in patients with early-stage disease (i.e., aortic sclerosis or mild AS). Methods: In total, 33 patients (18 males, 15 females; mean age 70 8 years) with aortic sclerosis or mild AS, who had never received statin treatment, were enrolled into the study. According to their baseline lipid levels, 17 patients were hypercholesterolemic and 16 normocholesterolemic. Hence, rather than apply randomization, all patients were administered atorvastatin at a moderate dose level. Plasma levels of three biomarkers of calcification were measured, namely osteoprotegerin (OPG), osteopontin (OPN), and soluble receptor activator of nuclear factor (NF)-kappa B ligand (sRANKL). Results: Plasma levels of all three biomarkers were decreased after atorvastatin treatment. OPG levels fell from 13.23 +/- 5.33 to 10.92 +/- 5.34 pmol/l (p <0.05), sRANKL from 105.36 +/- 69.47 to 86.74 +/- 71.36 ng/ml (p <0.05), and OPN from 31.60 +/- 20.29 to 28.45 +/- 15.98 ng/ml (p = NS). When comparing patients with no/mild valvular calcification to those with moderate valvular calcification, only the OPG level before atorvastatin was statistically higher in patients from the latter group: 11.44 +/- 4.51 versus 16.09 +/- 5.67 pmol/l (p <0.05). Conclusion: Atorvastatin, at a dose level of 20 mg per day, reduced the plasma levels of calcification biomarkers in patients with aortic sclerosis and mild AS. The pre-atorvastatin OPG level was significantly higher when the aortic valve was moderately calcified, despite a persistent low transvalvular gradient.