title: Impaired coronary artery distensibility is an endothelium-dependent process and is associated with vulnerable plaque composition.
abstract: Coronary endothelial-dependent microvascular dysfunction, an early reversible stage of coronary artery disease (CAD), is associated with poor clinical outcome. The current study investigated whether coronary artery distensibility index (CDI) is associated with: (i) coronary endothelial-dependent microvascular dysfunction and (ii) vulnerable plaque composition among subjects with non-obstructive CAD. Seventy-four subjects with non-obstructive CAD (luminal stenosis <30%) were studied. In 20 subjects with and without coronary endothelial-dependent microvascular dysfunction, coronary flow reserve (CFR) of target segment during intracoronary (IC) infusion of acetylcholine (Ach) and bolus injection of adenosine as well as CDI at rest of corresponding target segment were measured. In 54 subjects, plaque compositions and CDI at rest of 154 non-obstructive coronary segments as well as proximal segment without disease were measured by intravascular ultrasound (IVUS). CDI was defined as: [(Early-diastolic cross-sectional-area (CSA) - End-diastolic CSA of target segment)/(end-diastolic CSA of target segment × coronary-pulse-pressure) × 10(3) ]. There is a direct association between endothelial dysfunction and impaired CDI of a coronary segment both in the given coronary segment and corresponding microvessels in which a strong agreement between CDI and CFR Ach (r(2)  = 0·85, P = 0·0001) was observed. Multivariable regression-analysis showed that CDI was an independent predictor of the vulnerable plaque characteristics. The risk of impaired CDI was 125% higher in segments with necrotic core and 60% higher in segments with fibrofatty components as compared to normal segments (P = 0·001). In conclusions, the current study reveals that impaired CDI is an endothelial-dependent process of both given coronary segment and corresponding microvessels and is associated with vulnerable plaque composition.
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Naser
authors.initials: N
authors.lastname: Ahmadi
authors.affiliation: Mayo Clinic, Mayo Graduate School of Medicine, Rochester, MN, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz-Garcia
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Hajsadeghi
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Azen
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Mack
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Hodis
authors.affiliation: Mayo Clinic, Mayo Graduate School of Medicine, Rochester, MN, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000241:Adenosine / Q000008:administration & dosage; D000328:Adult; D019540:Area Under Curve; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D007269:Injections, Intra-Arterial; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D012372:ROC Curve; D012720:Severity of Illness Index; D018084:Ultrasonography, Interventional; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine; D000109:Acetylcholine
keywords: coronary artery disease; coronary artery distensibility; coronary endothelial-dependent microvascular dysfunction; coronary flow reserve; vulnerable plaque composition