TY - JOUR
T1 - Microvascular Resistance Reserve vs Coronary Flow Reserve to Assess Age-Related Trends in Coronary Microvascular Dysfunction
AU - Nijkamp, Timo
AU - Namba, Hanae F.
AU - Boerhout, Coen K.M.
AU - Lee, Joo Myung
AU - de Waard, Guus A.
AU - Mejía-Rentería, Hernán
AU - Hoshino, Masahiro
AU - Echavarria-Pinto, Mauro
AU - Meuwissen, Martijn
AU - Matsuo, Hitoshi
AU - Madera-Cambero, Maribel
AU - Eftekhari, Ashkan
AU - Effat, Mohamed A.
AU - Banerjee, Rupak
AU - Murai, Tadashi
AU - Marques, Koen
AU - Doh, Joon Hyung
AU - Jung, Ji Hyun
AU - Nam, Chang Wook
AU - Niccoli, Giampaolo
AU - Nakayama, Masafumi
AU - Tanaka, Nobuhiro
AU - Shin, Eun Seok
AU - van Es, René
AU - den Ruijter, Hester M.
AU - van der Harst, Pim
AU - Knaapen, Paul
AU - Koo, Bon Kwon
AU - Kakuta, Tsunekazu
AU - Escaned, Javier
AU - van Royen, Niels
AU - Christiansen, Evald H.
AU - Piek, Jan J.
AU - Damman, Peter
AU - van de Hoef, Tim P.
N1 - Publisher Copyright:
© 2026 The Authors.
PY - 2026/2/23
Y1 - 2026/2/23
N2 - 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.
AB - 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.
KW - ANOCA
KW - coronary artery disease
KW - coronary flow reserve
KW - coronary microvascular dysfunction
KW - microvascular resistance reserve
UR - https://www.scopus.com/pages/publications/105030058379
U2 - 10.1016/j.jcin.2025.11.019
DO - 10.1016/j.jcin.2025.11.019
M3 - Article
C2 - 41518358
AN - SCOPUS:105030058379
SN - 1936-8798
VL - 19
SP - 437
EP - 448
JO - JACC: Cardiovascular Interventions
JF - JACC: Cardiovascular Interventions
IS - 4
ER -