title: Systemic endothelial dysfunction in children with idiopathic pulmonary arterial hypertension correlates with disease severity.
abstract: BACKGROUND
  Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease manifested by progressive pulmonary vascular remodeling, compromised pulmonary blood flow and right heart failure. Most studies have explored how pulmonary endothelial function modulates disease pathogenesis. We hypothesize that IPAH is a progressive panvasculopathy, affecting both pulmonary and systemic vascular beds, and that systemic endothelial dysfunction correlates with disease severity. Recent studies have demonstrated systemic endothelial dysfunction in adults with pulmonary hypertension; however, adults often have additional comorbidities affecting endothelial function. Systemic endothelial function has not been explored in children with IPAH.
  
  
  METHODS
  In this single-center, prospective, cross-sectional study we examined brachial artery flow-mediated dilation (FMD), a nitric oxide-mediated, endothelial-dependent response, in children with IPAH and matched controls. FMD measurements were compared with clinical and echocardiographic measures of IPAH severity.
  
  
  RESULTS
  Thirteen patients and 13 controls were studied, ranging in age from 6 to 20 years. FMD was decreased in IPAH subjects compared with controls (5.1 ± 2.1% vs 9.7 ± 2.0%; p < 0.0001). In IPAH subjects, FMD correlated directly with cardiac index (R(2) = 0.34, p = 0.035), and inversely with tricuspid regurgitation velocity (R(2) = 0.57, p = 0.019) and right ventricular myocardial performance index (R(2) = 0.44, p = 0.028).
  
  
  CONCLUSIONS
  The presence of systemic endothelial dysfunction in children with IPAH and its strong association with IPAH severity demonstrate that IPAH is a global vasculopathy. Although morbidity in IPAH is typically associated with pulmonary vascular disease, systemic vascular changes may also relate to disease pathogenesis and progression. Further study into shared mechanisms of systemic and pulmonary endothelial dysfunction may contribute to future therapies for IPAH.
authors.affiliation: Children's Heart Center, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112, USA. defriedman@barnabashealth.org
authors.forename: Debbie
authors.initials: D
authors.lastname: Friedman
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Szmuszkovicz
authors.forename: Miklos
authors.initials: M
authors.lastname: Rabai
authors.forename: Jon A
authors.initials: JA
authors.lastname: Detterich
authors.forename: Jondavid
authors.initials: J
authors.lastname: Menteer
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000502:physiology; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D008297:Male; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000502:physiology; D012720:Severity of Illness Index; D055815:Young Adult