Rosuvastatin Affecting Aortic Valve Endothelium
Rosuvastatin Affecting Aortic Valve Endothelium
Objectives: The objective of this study was to test the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor on the progression of moderate to severe aortic stenosis as measured by echocardiography.
Background: Recent retrospective studies support the hypothesis that statins slow the progression of aortic stenosis.
Methods: We performed an open-label, prospective study evaluating 121 consecutive patients with asymptomatic moderate to severe aortic stenosis (aortic valve area ≥ 1.0 cm; mean age 73.7 ± 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months.
Results: Sixty-one patients (50.4%) with elevated LDL (159.7 ± 33.4 mg/dl), aortic valve velocity (3.65 ± 0.64 m/s), and aortic valve area (1.23 ± 0.42 cm) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 ± 37.4 mg/dl), aortic valve velocity (3.62 ± 0.61 m/s), and aortic valve area (1.20 ± 0.35 cm)received no statin. During a mean follow-up of 73 ± 24 weeks, the change in aortic valve area in the control group was -0.10 ± 0.09cm/year versus -0.05 ± 0.12cm/year in the rosuvastatin group (p=0.041). The increase in aortic valve velocity was 0.24 ± 0.30 m/s/year in the control group and 0.04 ± 0.38 m/s/year in the rosuvastatin group (p=0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group.
Conclusions: Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/ NCT00114491?order=1; NCT0014491). (J Am Coll Cardiol 2007;49:554-61) © 2007 by the American College of Cardiology Foundation
Calcific aortic stenosis is the most common indication for surgical valve replacement. The number of valve replacements is increasing because of the aging population. Currently, the only established therapy for patients with severe symptomatic aortic stenosis is surgical valve replacement. In 1997, Stewart et al. defined the independent risk factors associated with calcific aortic stenosis from the Cardiovascular Health Study, which include: elevated lipoprotein (a), low-density lipoprotein (LDL) cholesterol, hypertension, male gender, and smoking. These risk factors are similar to the risk factors defined for coronary heart disease by the Framingham Heart Study, and have been validated in other aortic stenosis risk factor databases.
Until recently, the mechanism of degenerative aortic stenosis was thought to be caused by a passive accumulation of calcium along the surface of the aortic valve leaflet. However, there are a growing number of experimental studies showing that aortic valve calcification is an active biological process that can be targeted with medical therapy such as statins.
Recently, this hypothesis has been confirmed with an increasing number of retrospective studies showing the effects of statins and angiotensin-converting enzyme inhibitors in slowing the progression of aortic valve stenosis.
We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors may slow the hemodynamic progression of calcific aortic stenosis and improve inflammatory markers that have been described clinically to affect the aortic valve endothelium. To test this hypothesis we examined the effects of rosuvastatin in an open-label prospective study to determine whether an HMG CoA reductase inhibitor can slow the progression of moderate to severe aortic stenosis as defined by echocardiographic parameters. We treated a population of patients with elevated cholesterol levels and moderate to severe aortic stenosis and measured the hemodynamic progression by echocardiography. We also monitored serum LDL cholesterol in these patients to determine whether rosuvastatin can slow the progression of aortic stenosis using a targeted therapeutic approach.
Objectives: The objective of this study was to test the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor on the progression of moderate to severe aortic stenosis as measured by echocardiography.
Background: Recent retrospective studies support the hypothesis that statins slow the progression of aortic stenosis.
Methods: We performed an open-label, prospective study evaluating 121 consecutive patients with asymptomatic moderate to severe aortic stenosis (aortic valve area ≥ 1.0 cm; mean age 73.7 ± 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months.
Results: Sixty-one patients (50.4%) with elevated LDL (159.7 ± 33.4 mg/dl), aortic valve velocity (3.65 ± 0.64 m/s), and aortic valve area (1.23 ± 0.42 cm) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 ± 37.4 mg/dl), aortic valve velocity (3.62 ± 0.61 m/s), and aortic valve area (1.20 ± 0.35 cm)received no statin. During a mean follow-up of 73 ± 24 weeks, the change in aortic valve area in the control group was -0.10 ± 0.09cm/year versus -0.05 ± 0.12cm/year in the rosuvastatin group (p=0.041). The increase in aortic valve velocity was 0.24 ± 0.30 m/s/year in the control group and 0.04 ± 0.38 m/s/year in the rosuvastatin group (p=0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group.
Conclusions: Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/ NCT00114491?order=1; NCT0014491). (J Am Coll Cardiol 2007;49:554-61) © 2007 by the American College of Cardiology Foundation
Calcific aortic stenosis is the most common indication for surgical valve replacement. The number of valve replacements is increasing because of the aging population. Currently, the only established therapy for patients with severe symptomatic aortic stenosis is surgical valve replacement. In 1997, Stewart et al. defined the independent risk factors associated with calcific aortic stenosis from the Cardiovascular Health Study, which include: elevated lipoprotein (a), low-density lipoprotein (LDL) cholesterol, hypertension, male gender, and smoking. These risk factors are similar to the risk factors defined for coronary heart disease by the Framingham Heart Study, and have been validated in other aortic stenosis risk factor databases.
Until recently, the mechanism of degenerative aortic stenosis was thought to be caused by a passive accumulation of calcium along the surface of the aortic valve leaflet. However, there are a growing number of experimental studies showing that aortic valve calcification is an active biological process that can be targeted with medical therapy such as statins.
Recently, this hypothesis has been confirmed with an increasing number of retrospective studies showing the effects of statins and angiotensin-converting enzyme inhibitors in slowing the progression of aortic valve stenosis.
We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors may slow the hemodynamic progression of calcific aortic stenosis and improve inflammatory markers that have been described clinically to affect the aortic valve endothelium. To test this hypothesis we examined the effects of rosuvastatin in an open-label prospective study to determine whether an HMG CoA reductase inhibitor can slow the progression of moderate to severe aortic stenosis as defined by echocardiographic parameters. We treated a population of patients with elevated cholesterol levels and moderate to severe aortic stenosis and measured the hemodynamic progression by echocardiography. We also monitored serum LDL cholesterol in these patients to determine whether rosuvastatin can slow the progression of aortic stenosis using a targeted therapeutic approach.
