Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with earlystages of coronary atherosclerosis

Background-Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the imp act of such risk factors as hypercholesterolemia. The goal of this study wa s to determine whether 6-month cholesterol-lowering therapy improves corona ry flow reserve in patients with angina, reduced flow reserve despite minim ally diseased coronary vessels or even normal angiogram, and mild to modera tely 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 [N- 13]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and af ter 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 significa ntly from 182 +/- 36 to 238 +/- 58 mL/min x 100 g (P<0.001) at follow-up. M inimum coronary resistance declined significantly from 0.51 +/- 0.12 to 0.4 0 +/- 0.14 mm Hg . mL(-1) . min x 100 g (P<0.001). Concomitantly, a regress ion of anginal symptoms was observed in most patients, Conclusions-Our results suggest that cholesterol-lowering therapy with simv astatin may improve overall coronary vasodilator capacity assessed noninvas ively by PET in patients with mild to moderate hypercholesterolemia. Conseq uently, intensive lipid-lowering therapy is considered a vasoprotective tre atment for selected patients in very early stages of coronary atheroscleros is with the potential of preventing further disease progression.