Improvement of blood oxygen diffusion capacity and anginal symptoms by cholesterol lowering with simvastatin

Objective: To assess the hypothesis that a cholesterol-lowering regimen with simvastatin would improve red blood cell (RBC) oxygen diffusion, and that such improvement would correlate with the intensity of anginal symptoms and with exercise electrocardiogram (ECG) changes Methods: Desaturated venous blood samples from 18 hypercholesterolemic volunteer subjects with exertional chest pain were collected before and after they took 40 mg of simvastatin daily for 12 weeks Blood samples were standardized to a hematocrit of 40% and a hemoglobin correction factor of 13 5 mg/dL, they were circulated in a closed-loop diffusion chamber to full oxygen saturation (O_2Sat) and then desaturated to about 70% O_2Sat was measured in a continuous blood oxygen diffusion system of our own design Plasma and RBC membrane cholesterol levels were determined Assessment of exertional chest pain and exercise ECGs were performed in blinded fashion Results: Mean oxygen diffusion levels were 30 7% higher after treatment (P=0 03) With the exception of HDL, all cholesterol parameter levels were reduced, by between 32 5% and 43 5% (P<0 001) All but 1 subject reported significant improvement in chest pain symptoms The exercise threshold for anginal symptoms increased by an average of 2 1-fold after treatment Only 3 subjects had a positive exercise ECG before treatment and 1 of them had a significant improvement after treatment Conclusions: The plasma and RBC membrane cholesterol levels are inversely associated with the transmembrane O ₂ diffusion rate of the RBC As blood cholesterol levels decrease, blood oxygen diffusion increases, anginal pain decreases, and the threshold for angina increases.