Coronary Microvascular Disease Assessed by 82‐Rubidium Positron Emission Tomography Myocardial Perfusion Imaging Is Associated With Small Vessel Disease of the Kidney and Brain

Background Coronary microvascular disease (CMD) may be part of a systemic small vessel disease that also manifests as neurological impairment and kidney disease. However, clinical evidence supporting a potential link is scarce. We assessed whether CMD is associated with an increased risk of small vessel disease in the kidney and brain. Methods and Results A retrospective multicenter (n=3) study of patients clinically referred to 82‐rubidium positron emission tomography myocardial perfusion imaging was conducted between January 2018 and August 2020. Exclusion criterion was reversible perfusion defects >5%. CMD was defined as myocardial flow reserve (MFR) ≤2. The primary outcome, microvascular event, was defined by hospital contact for chronic kidney disease, stroke, or dementia. Among 5122 patients, 51.7% were men, median age 69.0 [interquartile range, 60.0–75.0] years, 11.0% had left ventricular ejection fraction ≤40%, and 32.4% had MFR ≤2. MFR was associated with baseline estimated glomerular filtration rate after multivariable adjustment ( β =0.04 [95% CI, 0.03–0.05]; P <0.001). During a median follow‐up of 3.05 years, 383 (7.5%) patients suffered an event (253 cerebral and 130 renal), more frequently in patients with MFR ≤2 versus MFR >2 (11.6% versus 5.5%, P <0.001). MFR ≤2 was associated to outcome with a hazard ratio (HR) of 2.30 (95% CI, 1.88–2.81, P <0.001) and an adjusted HR of 1.62 (95% CI, 1.32–2.00, P <0.001). Results were consistent across subgroups defined by presence of irreversible perfusion defects, estimated glomerular filtration rate, diabetes, left ventricular ejection fraction, and previous revascularization. Conclusions This is the first large‐scale cohort study to link CMD to microvascular events in the kidney and brain. Data support the hypothesis that CMD is part of a systemic vascular disorder.