Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin

Background - Lipid-lowering therapy can improve endothelial function in patients with coronary artery disease (CAD) and hypercholesterolemia. Little is known about induced changes in myocardial microcirculation. This study prospectively investigated the temporal effects of lipid-lowering therapy with fluvastatin on coronary flow and flow reserve (CFR) in patients with CAD assessed by PET. Methods and Results - In an open clinical trial, CFR was studied in 15 patients with angiographically documented multivessel CAD and hypercholesterolemia (LDL > 160 mg/dL). Dynamic ¹³N-labeled ammonia PET imaging in conjunction with adenosine was used to assess regional and global CFR at baseline as well as at 2 and 6 months during treatment with fluvastatin (60 to 80 mg/d). Despite a rapid decrease in total cholesterol (29±6%) and LDL (37±9%), myocardial blood flow at rest and during stress was unchanged after 2 months of treatment (2.7±0.9 versus 2.5±0.6 mL · g^{- 1} · min^-1). At 6 months, stress blood flow as well as CFR increased significantly (3.4±1.0 mL · g^-1 · min^-1). No change in hemodynamic parameters was noted during the entire study. Nine of 15 patients increased CFR by > 20%. All responders demonstrated improvement in anginal symptoms, whereas nonresponders stated no change (n=4) or worsening of symptoms (n=2). The improvement in CFR was not related to the amount of lipid lowering and was independent of the severity of stenoses. Conclusions - Improvement in stress blood flow and CFR is delayed compared with the lipid-lowering effect of fluvastatin, suggesting a slow recovery of the vasodilatory response to adenosine.