Published Online
on December 29, 2003

A more recent version of this article appeared on January 6, 2004

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Submitted on May 30, 2003
Revised on July 29, 2003
Accepted on September 5, 2003

Angiotensin-Converting Enzyme Inhibitors and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Cardiac Syndrome X. Role of Superoxide Dismutase Activity

Carmine Pizzi MD, Olivia Manfrini MD, Fiorella Fontana MD, and Raffaele Bugiardini MD^*

From the Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, University of Bologna, Italy.

^* To whom correspondence should be addressed. E-mail: raffaele.bugiardini{at}unibo.it.

Background--Morbidity of patients with Syndrome X (SX; chest pain and normal coronary angiograms) is high and is associated with continuing episodes of chest pain and hospitalization. Impairment of microvascular endothelial function caused by increased oxidative stress has been suggested to be a mechanism of the disease. Superoxide dismutase (SOD) is the major antioxidant enzyme system of the vascular wall. This study sought to establish whether combination treatment with ACE inhibitors and statins reduces oxidative stress and improves quality of life of patients with cardiac SX.

Methods and Results--Forty-five patients with SX were randomly assigned to receive either a combination of ramipril (10 mg/d) and atorvastatin (40 mg/d) or placebo for 6 months. We determined the activity of extracellular SOD and its relation to flow-dependent endothelium-mediated dilation (FMD) and quality of life (exercise capacity and score with Seattle Angina Questionnaire [SAQ]) before and after treatment. After 6 months, patients with SX who received atorvastatin and ramipril had significantly reduced (P=0.001) SOD levels (188.1±29.6 U/mL). No significant changes were seen on placebo (262.9±48.8 U/mL). Reduction of SOD after therapy was negatively correlated with FMD (r=0.38; P=0.01) and positively with total cholesterol (r=-0.56; P<0.001). At follow-up, patients taking atorvastatin and ramipril improved their quality of life both in terms of exercise duration (by 23.46%) and SAQ (by 64.1%).

Conclusions--Six months of therapy with atorvastatin and ramipril improves endothelial function and quality of life of patients with SX. Reduced SOD activity may reflect low superoxide anion production. Benefits of these drugs may be related to reduction of oxidative stress.

Key words: syndrome X • endothelium • free radicals

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