Interrelation of coronary calcification, myocardial ischemia, and outcomes in patients with intermediate likelihood of coronary artery disease - A combined positron emission tomography/computed tomography study

Background - Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting coronary artery disease remains controversial, and its incremental prognostic value over myocardial perfusion is not well established. Methods and Results - We evaluated 695 consecutive intermediate-risk patients undergoing combined rest-stress rubidium 82 positron emission tomography (PET) perfusion imaging and CAC scoring on a hybrid PET-computed tomography (CT) scanner. The frequency of abnormal scans among patients with a CAC score >= 400 was higher than that in patients with a CAC score of 1 to 399 (48.5% versus 21.7%, P < 0.001). Multivariate logistic regression supported the concept of a threshold CAC score >= 400 governing this relationship (odds ratio 2.91, P < 0.001); however, the frequency of ischemia among patients with no CAC was 16.0%, and its absence only afforded a negative predictive value of 84.0%. Risk-adjusted survival analysis demonstrated a stepwise increase in event rates (death and myocardial infarction) with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging. Among patients with normal PET myocardial perfusion imaging, the annualized event rate in patients with no CAC was lower than in those with a CAC score >= 1000 (2.6% versus 12.3%, respectively). Likewise, in patients with ischemia on PET myocardial perfusion imaging, the annualized event rate in those with no CAC was lower than among patients with a CAC score >= 1000 (8.2% versus 22.1%). Conclusions - Although increasing CAC content is generally predictive of a higher likelihood of ischemia, its absence does not completely eliminate the possibility of flow-limiting coronary artery disease. Importantly, a stepwise increase occurs in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging.