BACKGROUND: Estimation of coronary artery calcification (CAC) can provide important prognostic information in patients with suspected coronary artery disease. OBJECTIVES: The authors aimed to investigate whether CAC evaluation offers additional insight into the association of stress electrocardiographic (ECG) changes with adverse outcomes in patients undergoing myocardial perfusion imaging (MPI). METHODS: Twelve thousand two hundred sixty-five patients (47% female, median: 64 (56-73) years, body mass index: 29 ± 7 kg/m RESULTS: During the median follow-up of 1.6 (IQR: 0.5-3.0) years, the primary outcome (3-year composite of death, myocardial infarction, or coronary revascularization, major adverse cardiac event [MACE]) occurred in 1,422 patients. Within participants with normal perfusion, MACE rate was the highest in patients with CAC with or without ischemic stress ECG (9.6% and 7%, respectively), and low event rates were observed in patients without CAC with or without ischemic stress ECG (0.5% and 1.9% respectively). In a subgroup analysis, all CAC grades (mild, moderate, severe) were independently associated with worse 3-year composite endpoint rates. In multivariable analysis, the presence of CAC was associated with MACE independent of ischemic ECG changes in both the overall cohort (P <
0.001) and when restricting the analysis to patients with normal perfusion (P <
0.05). CONCLUSIONS: In patients with normal single-photon emission computed tomography/CT MPI, CAC is strongly associated with adverse outcomes independent of ischemic ECG changes with low event rates in patients without CAC on attenuation CT irrespective of ischemic stress ECG changes.