Background: Previous studies provide evidence for a significant reduction of coronary flow reserve after ingestion of meals of different compositions. A possible role of hyperinsulinemia and increased free fatty acid levels, which are deleterious during acute myocardial ischemia and reperfusion, has been hypothesized. We assessed in patients with stable coronary disease the effects of high-fat meals(HFMs) and high-carbohydrate meals(HCMs) on ischemic threshold and stress left ventricular function on placebo and after partial fatty acid inhibition by trimetazidine(TMZ). Methods: Ten patients(9 men, age 68±7 years) were allocated to placebo and TMZ(40 mg TID), both administered in the 24 hours preceding testing, according to a randomized double-blind study design. All patients underwent stress(treadmill exercise testing according to the Bruce protocol) echocardiography after fasting(8 hours) and after an HFM and HCM(2 hours) either on placebo or on TMZ. Time to 1-mm ST-segment depression(time to 1 mm) and stress wall motion score index(WMSI) were evaluated. Results: An HFM did not affect exercise variables compared with fasting, whereas an HCM resulted in a reduction of the ischemic threshold(time to 1 mm from 402±141 to 292±123 seconds, P=.025). Compared with placebo, TMZ improved time to 1 mm after fasting, HFM, and HCM(432±153 vs 402±141, 439±118 vs 380±107, 377±123 vs 292±123, F1,9=26.91, P=.0006). Compared with placebo, on TMZ, stress WMSI decreased from 1.55±0.25 to 1.29±0.14 after fasting, from 1.57± 0.10 to 1.39±0.28 after HFM, and from 1.64±0.21 to 1.39±0.21 after HCM(F1,9=37.04, P=.0002). Interestingly, stress WMSI on TMZ was never different from rest WMSI on placebo. Conclusions: In patients with coronary disease, exercise testing after an HCM results in more severe myocardial ischemia compared with that after an HFM. The observed beneficial effects of the partial fatty acid inhibitor TMZ seem to be unrelated to meal composition and are possibly caused by the better glucose use induced by the drug. Background: Previous studies provide evidence for a significant reduction of coronary flow reserve after ingestion of meals of different compositions. A possible role of hyperinsulinemia and increased free fatty acid levels, which are deleterious during acute myocardial ischemia and reperfusion, has been hypothesized. in patients with stable coronary disease the effects of high-fat meals (HFMs) and high-carbohydrate meals (HCMs) on ischemic threshold and stress left ventricular function on placebo and after partial fatty acid inhibition by trimetazidine (TMZ). Methods: Ten patients (9 men, age 68 ± 7 years) were allocated to placebo and TMZ (40 mg TID), both administered 24 hours preceding testing, according to a randomized double-blind study design. All patients underwent stress to the Bruce protocol) echocardiography after fasting (8 hours) and after an HFM and HCM (2 hours) either on placebo or on TMZ. Time to 1-mm ST-segment depressio Results: An HFM did not affect exercise variables compared with fasting, an an HCM resulted in a reduction of the ischemic threshold (time to 1 mm from 402 ± 141 to 292 ± 123 seconds, P = .025). Compared with placebo, TMZ improved time to 1 mm after fasting, HFM, and HCM (432 ± 153 vs 402 ± 141, 439 ± 118 vs 380 ± 107, 377 ± 123 vs 292 ± 123, F1,9 = 26.91, P = .0006). Compared with TMZ, stress WMSI decreased from 1.55 ± 0.25 to 1.29 ± 0.14 after fasting, from 1.57 ± 0.10 to 1.39 ± 0.28 after HFM, and from 1.64 ± 0.21 to 1.39 ± 0.21 after HCM (F1, 9 = 37.04, P = .0002). Interestingly, stress WMSI on TMZ was never different from rest WMSI on placebo. Conclusions: In patients with coronary disease, exercise testing after an HCM results in more severe myocardial ischemia compared with that after an HFM. The observed beneficial effects of the partial fatty acid inhibitor TMZ seem to be unrelated to meal composition and are possi bly caused by the better glucose use induced by the drug.