Effect of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors on the Progression of Calcific Aortic Stenosis

Abstract

Background-Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis. Methods and Results-A retrospective study of 174 patients (mean age 68Ϯ12 years) with mild to moderate calcific aortic stenosis was conducted. Patients required normal left ventricular function, Յ2ϩ aortic regurgitation, and Ն2 echocardiograms performed at least 12 months apart. Fifty-seven patients (33%) received treatment with a statin; the remaining 117 (67%) did not. The statin group was older and had a higher prevalence of hypertension, diabetes mellitus, and coronary disease. During a mean follow-up of 21 months, patients treated with statin had a smaller increase in peak and mean gradient and a smaller decrease in aortic valve area. When annualized, the decrease in aortic valve area for the nonstatin group was 0.11Ϯ0.18 cm 2 compared with 0.06Ϯ0.16 cm 2 for those treated with a statin (Pϭ0.03). In multivariate analysis, statin usage was a significant independent predictor of a smaller decrease in valve area (Pϭ0.01) and a lesser increase in peak gradient (Pϭ0.02). Conclusions-Statin-treated patients, despite a higher risk profile for progression, had reduced aortic stenosis progression compared with those not treated with a statin. These data provide justification for a prospective randomized trial to substantiate whether statin therapy slows the progression of aortic stenosis.

ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

“…Previous studies have also reported an association of elevated serum LDL‐C with development and faster progression of AS 6, 46, 47, 48. In the present study, higher apoB/apoA‐I ratio was associated with faster AS progression independently of the level of LDL‐C, which did not reach significance level.…”

Ideal Cardiovascular Health and the Prevalence and Severity of Aortic Stenosis in Elderly Patients

“…These findings argue forcefully for efforts to prevent progression of AV disease to hemodynamic significance in elderly individuals. Although several studies suggested potential for treatment with hydroxymethylglutaryl–coenzyme A reductase inhibitors (statins) in this regard,49, 50 randomized clinical trials have failed to demonstrate efficacy of statin therapy to delay disease progression, assessed by either AV peak velocity or clinical outcomes, among people with mild‐to‐moderate AS. One potential explanation for the negative findings in these studies is the relatively advanced stage of disease process at the time of intervention.…”

Long-term effects of statins on arterial pressure and stiffness of hypertensives

“…[6][7][8] The mechanism of the reduction of BP by statins in hypertensive hyperlipidaemic patients involves the activation of endothelial nitric oxide synthase, 9 the downregulation of angiotensin II type 1 receptors, 10 and a reduction in the vascular production of reactive oxygen species. 11 In addition, the long-term administration of statins has been shown to inhibit the progression of aortic stenosis 12 and to reduce aortic stiffness, as assessed by PWV, in normotensive patients with hypercholesterolaemia. 13,14 Therefore, long-term statin administration may improve BP control and PWV in patients with uncontrolled hypertension and high serum cholesterol levels.…”