title: Microvascular Dysfunction as Opposed to Conduit Artery Disease Explains Sex-specific Chest Pain in Emergency Department Patients With Low to Moderate Cardiac Risk.
abstract: OBJECTIVE
  Chest pain is a common emergency department (ED) presentation that is often unexplained. Recent evidence suggests that disease of the microvessels (arterioles) as opposed to the coronary artery (conduit artery) could explain one third of these cases, particularly in women. Brachial artery reactivity (BAR) is a validated surrogate measure of coronary artery vasomotion.
  
  
  OBJECTIVE
  The goal of this study was to compare brachial artery conduit vessel function (BAR) and microvascular function (postischemic peak reactive hyperemia [RH]) in subjects with and without chest pain and grouped according to sex.
  
  
  METHODS
  This prospective cohort study was conducted from January through March 2010. Cases were patients admitted to an ED chest pain center with low to moderate risk of acute coronary syndrome; they were eligible for study if their creatinine level was <2.0 mg/dL and systolic blood pressure was >100 mm Hg or <180 mm Hg. Asymptomatic healthy volunteers on no medications were recruited as control subjects. BAR as a change in brachial artery diameter in response to transient forearm ischemia (endothelium-dependent vasodilation) and RH as a change in flow velocities were measured with a high-resolution ultrasound. Telephone follow-up visits were made at 1 month for recurrence of chest pain and recidivism.
  
  
  RESULTS
  A total of 57 patients and 21 control subjects were enrolled; there was 100% follow-up at 1 month. Most patients (86%) had at least 1 cardiac risk factor. Neither BAR nor RH varied significantly between patients and control subjects (P > 0.05). Symptomatic men had lower mean BAR than women (2.67% vs 6.22%; P < 0.01), even when normalized for shear stress (P = 0.01). Conversely, women with chest pain had lower RH compared with men (2.85 vs 4.61; P = 0.01). The sex-specific differences adjusted for age and Framingham risk scores persisted for BAR (P = 0.003) and RH (P = 0.002). Of 57 patients, 53% had recurrent pain, and 4 returned to the hospital within 1 month.
  
  
  CONCLUSIONS
  Differences in BAR and RH in patients ruled out for myocardial infarction suggest that the pathophysiology of acute chest pain might be sex-specific. Men with chest pain exhibited lower BAR, indicating peripheral conduit artery dysfunction. Conversely, women with chest pain exhibited lower postischemic peak hyperemia, indicative of peripheral microvascular dysfunction. Sex differences in pathophysiology of chest pain and vascular dysfunction could inform development of effective therapeutics for patients with recurrent or persistent chest pain in the absence of obstructive coronary artery disease.
authors.affiliation: Department of Emergency Medicine, Yale School of Medicine, New Haven, Connecticut. Electronic address: basmah.safdar@yale.edu.
authors.forename: Basmah
authors.initials: B
authors.lastname: Safdar
authors.affiliation: Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Asad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Emergency Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Gail
authors.initials: G
authors.lastname: D'Onofrio
authors.affiliation: Department of Internal Medicine, Section of Cardiology, NYU School of Medicine, New York, New York.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Katz
mesh_terms: D000328:Adult; D001794:Blood Pressure; D001916:Brachial Artery / Q000378:metabolism; D016022:Case-Control Studies; D002637:Chest Pain / Q000209:etiology*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000473:pathology; D004636:Emergency Service, Hospital; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014664:Vasodilation
keywords: brachial artery reactivity; chest pain; emergency department; reactive hyperemia; sex difference