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Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients
L A Simons1, D Sullivan, J Simons
1University of New South Wales Lipid Research Department, St. Vincent's Hospital, Darlinghurst, Australia. exb0072@vmsuser.acsu.unsw.edu.au
Insights
Statins like atorvastatin and simvastatin significantly improved endothelial function in patients with severe hypercholesterolemia. This enhancement in flow-mediated dilation suggests a potential reduction in future coronary events.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Atherosclerosis Research
Background:
- Endothelial dysfunction is a key early indicator in the development of atherosclerosis.
- Severe primary hypercholesterolemia significantly impairs arterial endothelial physiology.
Purpose of the Study:
- To evaluate the impact of atorvastatin and simvastatin on endothelial function in patients with severe primary hypercholesterolemia.
- To assess changes in flow-mediated endothelium-dependent dilatation (FMD) following statin therapy.
Main Methods:
- Non-invasive brachial ultrasound was used to measure FMD in response to reactive hyperemia.
- Patients with hypercholesterolemia were treated with either atorvastatin or simvastatin plus cholestyramine.
- Lipid profiles and FMD were assessed at baseline and after 30 weeks of treatment.
Main Results:
- Both atorvastatin and simvastatin plus cholestyramine significantly improved impaired FMD in patients.
- Atorvastatin therapy led to median reductions of 41% in total cholesterol and 46% in LDL cholesterol.
- Simvastatin plus cholestyramine resulted in median reductions of 32% in total cholesterol and 39% in LDL cholesterol.
Conclusions:
- Treatment with atorvastatin or simvastatin plus cholestyramine effectively improves endothelial dysfunction in primary hypercholesterolemia.
- The observed improvement in endothelial function may contribute to the prevention of future coronary events.
Abstract:
Endothelial dysfunction is an important early event in atherogenesis. Changes in arterial endothelial physiology were studied in patients with severe primary hypercholesterolaemia participating in an ongoing clinical trial evaluating atorvastatin and simvastatin. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. Patients were studied upon entry while still using simvastatin 40 mg daily and again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients received atorvastatin titrated up to 80 mg daily and 12 patients received simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12), followed by a final ultrasound study. During simvastatin washout, total and low density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%, respectively. During atorvastatin therapy, total and LDL cholesterol fell by a median of 41 and 46%, respectively, triglycerides fell by 45%, and high density lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients at baseline showed evidence of impaired FMD and this improved significantly on either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical response in healthy subjects would be from + 8 to + 9%. FMD at baseline was correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in primary hypercholesterolaemia was improved by treatment with atorvastatin or simvastatin plus cholestyramine and this effect may result in the prevention of future coronary events.