High cholesterol levels have been shown to adversely affect the endothelium vasodilatory capacity. This defect appears to be involved in the pathogenesis of myocardial ischemia. Lowering cholesterol levels restores some of that function. This could account for the rapid reduction in cardiovascular morbidity in patients with known coronary artery disease and average cholesterol levels following a short course of pravastatin therapy. Mostaza and colleagues evaluated the impact of pravastatin therapy on myocardial perfusion in patients with coronary artery disease and average cholesterol levels.
A randomized, placebo-controlled design with a crossover component was conducted for 32 weeks. All 20 participants had known coronary artery disease, a fasting low-density lipoprotein (LDL) cholesterol level of less than 160 mg per dL (4.15 mmol per L) at the time of screening and reversible perfusion defects. All patients were randomly assigned to receive 20 mg of pravastatin or placebo daily in a single nocturnal dose for 16 weeks. At the end of this period, patients were crossed over. Lipid levels were obtained and lipoprotein analysis performed along with dipyridamole stress thallium-201 single-photon emission computed tomography (SPECT) at the end of each 16-week period. The SPECT results were analyzed by two independent observers.
The average total and LDL cholesterol levels were 214 ± 29 mg per dL (5.50 ± 0.75 mmol per L) and 148 ± 25 mg per dL (3.80 ± 0.65 mmol per L), respectively, during the placebo portion of the study. With pravastatin therapy, the average total and LDL cholesterol levels were 170 ± 23 mg per dL (4.40 ± 0.60 mmol per L) and 103 ± 23 mg per dL (2.65 ± 0.60 mmol per L), respectively. The evaluation of the SPECT results revealed that the summed stress and rest scores were better in the pravastatin group than in the placebo group. Quantitative analysis also showed smaller perfusion defects in the pravastatin group than in the placebo group during dipyridamole stress. No difference was seen at rest.
The authors conclude that myocardial perfusion defects improved after 16 weeks of pravastatin therapy even in patients with average cholesterol levels. Because improvement occurred in a short time, they suggest that the benefits are related to functional improvement and not anatomic changes.