Timo Nijkamp, Hanae F. Namba, Coen K.M. Boerhout, Joo Myung Lee, Guus A. de Waard, Hernán Mejía‐Rentería, Masahiro Hoshino, Mauro Echavarría-Pinto, Martijn Meuwissen, Hitoshi Matsuo, Maribel Madera‐Cambero, Ashkan Eftekhari, Mohamed A. Effat, Rupak K. Banerjee, Tadashi Murai, Koen Marques, Joon-Hyung Doh, Ji Hyun Jung, Chang-Wook Nam, Giampaolo Niccoli, Masafumi Nakayama, Nobuhiro Tanaka, Eun‐Seok Shin, René van Es, Hester M. den Ruijter, Pim van der Harst, Paul Knaapen, Bon-Kwon Koo, Tsunekazu Kakuta, Javier Escaned, Niels van Royen, Evald H. Christiansen, Jan J. Piek, Peter Damman, Tim P. van de Hoef
BACKGROUND: Advancing age is associated with epicardial atherosclerosis and coronary microvascular dysfunction (CMD), complicating reliable assessment of CMD using coronary flow reserve (CFR). Whether prevalence of functional and structural CMD varies with age remains unclear. OBJECTIVES: The authors sought to evaluate the prevalence of CMD endotypes by age strata and compare CFR with microvascular resistance reserve (MRR) for diagnosis and stratification. METHODS: Data from 1,704 patients (2,283 lesions) with stable angina in the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry) were analyzed, including obstructive (fractional flow reserve ≤0.80) and nonobstructive (fractional flow reserve >0.80) lesions. CMD was classified as no CMD (MRR ≥3.0), functional CMD (MRR <3.0, normal resistance), or structural CMD (MRR <3.0, abnormal resistance). CMD classification was repeated using CFR (<2.5 abnormal). Patients were stratified per age decade: <50, 50-59, 60-69, 70-79, and ≥80 years. RESULTS: CMD prevalence by MRR was 48.2%, and increased across age strata (37.2% to 78.0%; P < 0.001), driven by structural CMD (10.9% to 40.0%; P < 0.001), while functional CMD prevalence remained unchanged (26.3% to 38.0%; P = 0.220). Age independently predicted functional (OR/y: 1.02; P < 0.001) and structural CMD (OR/y: 1.05; P < 0.001). In obstructive lesions, age predicted structural CMD (OR/y: 1.03; P = 0.0055); in nonobstructive lesions, age predicted functional (OR/y: 1.02; P = 0.0032) and structural CMD (OR/y: 1.06; P < 0.001). Overall CMD prevalence by CFR exceeded MRR across groups (53.3% vs 48.2%; P < 0.001), irrespective of epicardial disease. CONCLUSIONS: Structural CMD increases with age regardless of obstructive CAD, while functional CMD prevalence increases only in nonobstructive CAD. CFR may overestimate CMD in epicardial disease, whereas MRR provides a more consistent assessment regardless of obstructive CAD, underscoring the need for prospective studies on their clinical relevance.