Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community

OBJECTIVES: This study was designed to analyze the association among cholesterol levels, lipid-lowering treatment, and progression of aortic stenosis (AS) in the community. BACKGROUND: Aortic stenosis is a progressive disease for which there is no known medical treatment to prevent or slow progression. Despite plausible pathologic mechanisms linking hypercholesterolemia to AS progression, clinical studies have been inconsistent and affected by referral bias, and the role of lipid-lowering therapy is uncertain. METHODS: We determined the association between blood cholesterol levels and progression of native AS (assessed by Doppler echocardiography at baseline and at least six months later; mean interval, 3.7 ± 2.3 years) in a community-based study of 156 patients (age 77 ± 12 years; 90 men). Thirty-eight patients received statin treatment during follow-up. RESULTS: In untreated subjects, mean gradient increased from 22 ± 12 mm Hg to 39 ± 19 mm Hg, and aortic valve area (AVA) decreased from 1.20 ± 0.35 cm² to 0.91 ± 0.33 cm² (both p < 0.001). The annualized change in AVA was -0.09 ± 0.17 cm²/year (-7% ± 13%/year). Neither total cholesterol (r = -0.01, p = 0.92) nor low-density lipoprotein cholesterol (r = 0.01; p = 0.88) showed a significant correlation to AS progression. Nevertheless, progression of AS was slower in patients receiving statins compared with untreated patients (decrease in AVA -3 ± 10% vs. -7 ± 13% per year, respectively; p = 0.04), even when adjusted for age, gender, cholesterol, and baseline valve area (p = 0.04). The association of statin treatment with slower progression was confirmed when analysis was restricted to patients coming for a systematic follow-up (p = 0.02). The odds ratio of AS progression with statin treatment was 0.46 (95% confidence interval, 0.21 to 0.96). CONCLUSIONS: In the community, progression of AS shows no trend of association with cholesterol levels. Statin treatment, however, is associated with slower progression, suggesting that the effects of statin treatment on progression of AS should be pursued with appropriate clinical trials.