Independent prognostic significance of myocardial flow reserve over coronary artery calcium, myocardial perfusion, and clinical variables in patients without known coronary artery disease, according to diabetes status

Objective: To explore differences in prevalence and prognosis associated with reduced myocardial flow reserve (MFR) in patients without known coronary artery disease (CAD) based on diabetes status. Methods: Of 2639 patients without known CAD who underwent rubidium positron emission tomography myocardial perfusion imaging (MPI), 818 patients (31%) had diabetes. Reduced MFR was defined as MFR <2.0. Coronary artery calcium (CAC) score was categorized as 0, 1-99, 100-399, and ≥400. Ischemic total perfusion deficit (TPD) was categorized as <1%, 1-<5%, and ≥5%. Outcome variables were all-cause death (ACD) and non-fatal myocardial infarction (MI). Results: During the median follow-up of 4.1 years, 574 (21.8%) ACD/MI occurred (204 [25.1%] diabetic patients, 370 [20.3%] nondiabetic patients). In multivariable Cox analysis, reduced MFR was associated with increased ACD/MI in patients with diabetes (per .1 decrease: HR: 1.04, 95% CI: 1.02-1.06, P < .001) and patients without diabetes (per .1 decrease: HR: 1.03, 95% CI: 1.02-1.04, P < .001). No interaction existed between diabetes and MFR for ACD/MI risk regardless of CAC or ischemic burden (all P > .05). Adding MFR to the risk prediction model of clinical, conventional MPI findings, and CAC improved the discrimination for clinical outcomes in both groups (DM: .003, non-DM: <.001, respectively). Conclusion: Reduced MFR was more common in patients with diabetes and an important independent prognostic marker over CAC and clinical variables. The association between MFR and ACD/MI risk did not differ between patients with and without diabetes who had no prior CAD, regardless of CAC and ischemic burden.