title: Impact of insulin resistance on ventricular function in pulmonary arterial hypertension.
abstract: BACKGROUND
  Insulin resistance (IR) is an independent prognostic marker in pulmonary arterial hypertension (PAH), although the mechanism by which it engenders risk is unknown. We prospectively investigated the clinical, laboratory, hemodynamic, and echocardiographic characteristics of insulin-sensitive (IS) and IR patients with PAH.
  
  
  METHODS
  This was a prospective cohort study including well-phenotyped patients with PAH proven at cardiac catheterization. Patients were classified as IS or IR on the basis of the well-validated triglyceride/high-density lipoprotein-cholesterol ratio. Clinical, laboratory, and hemodynamic characteristics were compared between cohorts. Distance walked on the 6-minute walk test (6MWT) and echocardiograms were compared between IS and IR for the sub-set of patients that had these tests within 1 month of cardiac catheterization.
  
  
  RESULTS
  Of the 111 PAH patients enrolled, 59 were IS, 25 were IR, and 27 were classified as indeterminate. Mean age was 45.8 ± 15.0 years. IR was associated with worse New York Heart Association class (p = 0.02). There were no differences in hemodynamics, biomarkers, 6MWT distance, or parameters of right ventricular function (i.e., tricuspid annular plane systolic excursion, myocardial performance index, and fractional area change) between groups. Despite similar systemic vascular resistance, parameters of left ventricular diastolic function were more favorable for IS vs IR, including mitral inflow E wave velocity (82 ± 17 vs. 64 ± 19 msec, p = 0.02), E/A ratio (1.2 ± 0.4 vs. 0.8 ± 0.2, p = 0.01), and lateral mitral valve E' velocity (13.9 ± 3.5 vs. 10.4 ± 2.2 msec, p = 0.01).
  
  
  CONCLUSIONS
  IR is associated with worse functional class and diastology compared with IS in PAH, although other prognostic parameters are similar.
authors.affiliation: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California; Division of Pulmonary & Critical Care Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Brunner
authors.affiliation: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Skhiri
authors.affiliation: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California; Division of Pulmonary & Critical Care Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Olga
authors.initials: O
authors.lastname: Fortenko
authors.affiliation: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hsi
authors.affiliation: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Francois
authors.initials: F
authors.lastname: Haddad
authors.affiliation: Division of Pulmonary & Critical Care Medicine, Stanford University School of Medicine, Stanford, California; Center for Health Policy/Center for Primary Care and Outcomes Research, Stanford, California.
authors.forename: Nayer
authors.initials: N
authors.lastname: Khazeni
authors.affiliation: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California; Division of Pulmonary & Critical Care Medicine, Stanford University School of Medicine, Stanford, California. Electronic address: zamanian@stanford.edu.
authors.forename: Roham T
authors.initials: RT
authors.lastname: Zamanian
mesh_terms: D000328:Adult; D006328:Cardiac Catheterization; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016138:Walking / Q000502:physiology
keywords: diastolic dysfunction; insulin resistance; myocardial function; pulmonary arterial hypertension; right ventricle