Microvascular Resistance Reserve vs Coronary Flow Reserve to Assess Age-Related Trends in Coronary Microvascular Dysfunction
Year: 2026
Type: article
Abstract: 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.
Authors: Timo Nijkamp, Hanae F. Namba, Coen K.M. Boerhout, Joo Myung Lee, Guus A. de Waard, Hernán Mejía-Rentería, Masahiro Hoshino, Mauro Echavarria-Pinto, Martijn Meuwissen, Hitoshi Matsuo, Maribel Madera-Cambero, Ashkan Eftekhari, Mohamed A. Effat, Rupak 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
Institutions: University Medical Center Utrecht, Amsterdam University Medical Centers, Samsung Medical Center, Sungkyunkwan University, Radboud University Medical Center, Universidad Complutense de Madrid, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Tsuchiura Kyodo General Hospital, Autonomous University of Queretaro, Institute for Social Security and Services for State Workers, Amphia Ziekenhuis, Gifu Heart Center, Tergooi, Aarhus University Hospital, University of Cincinnati, Cincinnati VA Medical Center, Inje University Ilsan Paik Hospital, Sejong General Hospital, Keimyung University Dongsan Medical Center, Keimyung University Dongsan Hospital, University of Parma, Tokyo Medical University Hachioji Medical Center, University of Ulsan, Ulsan University Hospital, Utrecht University, Seoul National University, Seoul National University Hospital
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Funder: Hartstichting
OpenAlex ID: W7119821302