title: Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.
abstract: BACKGROUND
  HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.
  
  
  METHODS
  We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.
  
  
  RESULTS
  Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.
  
  
  CONCLUSIONS
  Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH.
authors.affiliation: Department of Cardiovascular Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Rushi V
authors.initials: RV
authors.lastname: Parikh
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Division of Endocrinology and Metabolism, San Francisco VA Medical Center, San Francisco, California, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: San Francisco General Hospital Cardiology Division, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Heringer
authors.affiliation: San Francisco General Hospital Cardiology Division, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Macgregor
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: San Francisco General Hospital Positive Health Program, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: San Francisco General Hospital Cardiology Division, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: San Francisco General Hospital Cardiology Division, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D000328:Adult; D001794:Blood Pressure; D006328:Cardiac Catheterization; D004452:Echocardiography; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000503:physiopathology; D013599:Systole
chemical_list: D019332:Endothelin-1