Exercise-induced vasomotion of angiographically normal and stenotic coronary arteries improves after cholesterol-lowering drug therapy with bezafibrate

Objectives.

We attempted to determine whether the coronary vasomotor response to exercise improves after cholesterol-lowering drug therapy with bezafibrate.

Background.

Hypercholesterolemia and other coronary risk factors are associated with impaired endothelium-dependent coronary vasomotor response to physiologic or pharmacologic stimuli, even in the absence of overt coronary atherosclerosis. It is still unknown whether the coronary artery vasomotor response to dynamic exercise improves under cholesterol-lowering drug therapy.

Methods.

Of 15 male patients (age 51 ± 7 years [mean ± SD]) included in the study, 7 had markedly elevated cholesterol levels (≥6.5 mmol/liter, therapy group), and 8 had normal or slightly elevated cholesterol levels (<6.5 mmol/liter, control group). At baseline and after 7 months of cholesterol-lowering therapy with bezafibrate (400 mg/day) in the therapy group, coronary vasomotor response to dynamic exercise (percent change in cross-sectional vascular area at maximal exercise vs. rest [100%]) in normal and stenotic, previously dilated vessels was assessed by quantitative coronary angiography.

Results.

During follow-up, total serum cholesterol levels in the therapy group decreased from 7.8 ± 1.1 to 5.8 ± 1.1 mmol/liter (p = 0.0001) and did not change significantly in the control group (from 5.4 ± 0.9 to 6.0 ± 1.2 mmol/liter, p = NS). Exercise-induced vasomotor response (at similar work loads in the therapy and control groups) in both normal and dilated stenotic coronary arteries improved significantly in the therapy group, from 100 ± 9% to 109 ± 7% (p = 0.0001, cross-sectional area at rest 100%) and from 80 ± 11% to 106 ± 7% (p = 0.0002), respectively, but did not improve during follow-up in the control group.

Conclusions.

The present study indicates that cholesterol-lowering drug therapy with bezafibrate for 7 months improves exercise-induced vasomotion of angiographically normal coronary arteries. Seven months after coronary angioplasty, the reduction in serum cholesterol levels is, at least in part, associated with a restoration of the initially disturbed vasomotor response of stenotic vessel segments to exercise.