C-reactive protein (CRP) is a marker of inflammation and predicts outcome in apparently healthy subjects and patients with coronary artery disease. Systemic inflammation is present in patients with aortic valve stenosis (AS). The aim of this prospective study was to assess whether CRP levels predict the progression of AS severity. Blood samples for high-sensitivity CRP measurements and echocardiographic data were obtained in 43 patients (70% men; mean age 73 +/- 8 years) with asymptomatic degenerative AS at study entry. On the basis of repeat echocardiographic assessment at 6 months, patients were grouped as (1) slow progressors (a decrease in aortic valve area [AVA] <0.05 cm2 and/or an increase in aortic peak velocity <0.15 m/s) and (2) rapid progressors (a decrease in AVA > or =0.05 cm2 and/or an increase in aortic peak velocity > or =0.15 m/s). Plasma CRP levels were significantly higher in rapid progressors than slow progressors (median 5.1 [range 2.3 to 11.3] vs 2.1 [range 1.0 to 3.1] mg/L, p = 0.007). In multivariate analysis, CRP levels >3 mg/L were independently associated with rapid AS progression (odds ratio 9.1, 95% confidence interval 2.2 to 37.3). In conclusion, CRP levels are higher in patients with degenerative AS who show rapid valve disease progression. These findings suggest that inflammation may have a pathogenic role in degenerative AS.