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CLINICAL STUDIES

Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels

Jose M. Mostaza, MD, PhD^a, María V. Gomez, MD, PhD^a, Felix Gallardo, MD^a, María L. Salazar, MD, PhD^b, Raquel Martín-Jadraque, MD, PhD^a, Leandro Plaza-Celemín, MD^b, Isidoro Gonzalez-Maqueda, MD, PhD and Luís Martín-Jadraque, MD, PhD

^a Atherosclerosis Unit, Nuclear Medicine Service of the Centro de Investigaciones Clínicas del Instituto de Salud Carlos III, Madrid, Spain
^b the Atherosclerosis Unit, Cardiology Service of the Centro de Investigaciones Clínicas del Instituto de Salud Carlos III, Madrid, Spain
Coronary Unit of Hospital "La Paz," Madrid, Spain

Manuscript received December 3, 1998; revised manuscript received July 30, 1999, accepted October 5, 1999.

Reprint requests and correspondence: Dr. Jose M. Mostaza, Unidad de Arteriosclerosis, Centro de Investigaciones Clínicas Carlos III, Sinesio Delgado, 10, 28029 Madrid, Spain
jmostazap{at}medynet.com

OBJECTIVES

We sought to evaluate whether pravastatin treatment increases myocardial perfusion, as assessed by thallium-201 single-photon emission computed tomographic (SPECT) dipyridamole testing, in patients with coronary artery disease (CAD) and average cholesterol levels.

BACKGROUND

Previous studies in hypercholesterolemic patients have demonstrated that cholesterol reduction restores peripheral and coronary endothelium-dependent vasodilation and increases myocardial perfusion.

METHODS

This was a randomized, placebo-controlled study with a cross-over design. Twenty patients with CAD were randomly assigned to receive 20 mg of pravastatin or placebo for 16 weeks and then were crossed over to the opposite medication for a further 16 weeks. Lipid and lipoprotein analysis and dipyridamole thallium-201 SPECT were performed at the end of each period. The SPECT images were visually analyzed in eight myocardial segments using a 4-point scoring system by two independent observers. A summed stress score and a summed rest score were obtained for each patient. Quantitative evaluation was performed by the Cedars-Sinai method. The magnitude of the defect was expressed as a percentage of global myocardial perfusion.

RESULTS

Total and low density lipoprotein cholesterol levels during placebo were 214 ± 29 mg/dl and 148 ± 25 mg/dl, respectively. These levels with pravastatin were 170 ± 23 mg/dl and 103 ± 23 mg/dl, respectively. The summed stress score and summed rest score were lower with pravastatin than with placebo (7.2 ± 2.3 vs. 5.9 ± 2.3, p = 0.012 and 3.2 ± 1.6 vs. 2.4 ± 2.2, p = 0.043, respectively). Quantitative analysis showed a smaller perfusion defect with pravastatin (29.2%) as compared with placebo (33.8%) (p = 0.021) during dipyridamole stress. No differences were found at rest.

CONCLUSIONS

Reducing cholesterol levels with pravastatin in patients with CAD improves myocardial perfusion during dipyridamole stress thallium-201 SPECT.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANOVA = analysis of variance   CAD = coronary artery disease   HDL = high density lipoprotein   HMG-CoA = hydroxymethylglutaryl coenzyme A   LDL = low density lipoprotein   PET = positron emission tomography   SPECT = single-photon emission computed tomography

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