Interplay between subclinical calcified atherosclerosis and coronary microvascular dysfunction in patients with normal perfusion imaging

Aim Coronary microvascular dysfunction (CMD) and epicardial atherosclerosis often coexist and share common risk factors, yet their interplay remains poorly characterized, especially among patients with normal perfusion on ⁸²Rb PET. Methods: A total of 7273 consecutive patients (2010−2020) without known coronary artery disease, normal ⁸²Rb PET perfusion, and concomitantly measured CAC were studied. Multiple linear regression assessed associations between CAC and MBFR, adjusting for demographics, risk factors, symptoms, and imaging data. We tested interactions of age, sex, diabetes, and symptoms with CAC. Logistic regression evaluated the association of CAC with CMD (MBFR <2). Results: Mean age was 65.4 (12.4) years, 64 % were women. CMD was present in 44 % and CAC > 0 in 74 % of patients. Of patients with CMD, 79 % had CAC > 0. Among those with CAC >0, 44 % had CMD, vs. 31 % among CAC = 0. There was a modest inverse correlation between MBFR and CACS, r = − 0.18, p < 0.001. In multivariable analyses, each 100-unit increase in CAC was associated with a 4 % higher odds of CMD (OR 1.04 [95 % CI: 1.03–1.05], p < 0.001). Older age, female sex, hypertension, diabetes, dyspnea, resting tachycardia and lower left ventricular ejection fraction also predicted lower MBFR, collectively explaining only 20 % (R² = 0.20) of MBFR variance. No interactions were significant (p > 0.1). Conclusion: In this cohort with normal perfusion imaging, increased CAC burden was associated with a higher likelihood of CMD, suggesting frequent co-occurrence of epicardial atherosclerosis and CMD. Absence of CAC does not preclude CMD.