The Prognostic Interplay of Coronary Artery Calcium Volume and Density with Myocardial Flow Reserve and Incident Cardiovascular Events

Abstract Background It is important to evaluate the relationship between coronary plaque characteristics and myocardial blood flow (MBF) to determine coronary phenotypes that may predispose to cardiovascular disease. Objectives To study the association between coronary artery calcium (CAC) volume and density and positron emission tomography (PET)-derived myocardial flow reserve (MFR) and their relationship with incident cardiovascular disease. Methods The study population consisted of consecutive patients who were referred for clinically indicated PET myocardial perfusion imaging between 2019 and 2024. CAC was assessed in a separate gated scan done just prior to PET and calculated using the Agatston score. Since the Agatston score includes calcified plaques (≥130 HU), soft and low-density plaques were not assessed. MFR was calculated as the ratio of stress to rest MBF. Patients with CAC=0 and those with known CAD were excluded. Results The study population consisted of 3,884 individuals with mean (SD) age 69 (±10.5) years. When CAC volume and density were included in the same model, CAC density was positively associated with MFR (β coefficient= 0.10, 95% CI 0.06, 0.15) and CAC volume was inversely associated (β coefficient -0.08, 95% CI -0.10, -0.05). During a median follow-up of 13.7 months, the primary outcome (death/myocardial infarction) occurred in 218 individuals (5.6%). When CAC volume and density were included in the same model including demographics and cardiovascular risk factors, CAC density was inversely and significantly associated with the primary outcome (HR= 0.67, 95% CI 0.47, 0.96) while CAC volume was positively and significantly associated with it (HR= 1.57, 95% CI 1.34, 1.82). Results were no longer significant after further adjustment for CAC, stress test parameters and MFR. Conclusion At any level of CAC volume, higher CAC density is significantly associated with higher MFR but not associated with risk of death/myocardial infarction.