Background: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin).
Methods: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients.
Conclusions: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.