Background—Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in patients with angina, reduced flow reserve despite minimally diseased coronary vessels or even normal angiogram, and mild to moderately elevated LDL levels on average.

Methods and Results—We noninvasively investigated 23 consecutive patients (18 men, 5 women; mean age, 56±7.6 years) with a mean LDL level of 165±34 mg/dL at baseline by PET for myocardial blood flow measurement with [¹³N]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and after lipid-lowering therapy with simvastatin for 6 months. Between baseline and the 6-month follow-up, total cholesterol concentration fell from 241±44 to 168±34 mg/dL, and the LDL level decreased from 165±34 to 95±26 mg/dL (P<0.001). Overall, coronary flow reserve increased from 2.2±0.6 to 2.64±0.6 (P<0.01). Maximal coronary flow increased significantly from 182±36 to 238±58 mL/min×100 g (P<0.001) at follow-up. Minimum coronary resistance declined significantly from 0.51±0.12 to 0.40±0.14 mm Hg · mL⁻¹ · min×100 g (P<0.001). Concomitantly, a regression of anginal symptoms was observed in most patients.

Conclusions—Our results suggest that cholesterol-lowering therapy with simvastatin may improve overall coronary vasodilator capacity assessed noninvasively by PET in patients with mild to moderate hypercholesterolemia. Consequently, intensive lipid-lowering therapy is considered a vasoprotective treatment for selected patients in very early stages of coronary atherosclerosis with the potential of preventing further disease progression.