title: Pulmonary hypertension is related to peripheral endothelial dysfunction in heart failure with preserved ejection fraction.
abstract: BACKGROUND
  Pulmonary hypertension (PH) and collagen metabolism abnormalities are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in pulmonary arterial hypertension. Our aim is to determine whether PH is associated with PED and impaired collagen metabolism in patients with HFpEF.;
  
  
  RESULTS
  Flow-mediated dilation of the brachial artery, matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue metalloproteinase inhibitor 1, and C-terminal propeptide of type I procollagen were determined in 28 patients with HFpEF and 42 hypertensive controls. Patients with systolic pulmonary artery pressure >35 mm Hg on echocardiogram underwent a right heart catheterization. Patients with HFpEF had more severe PED than controls: flow-mediated dilation 1.95% (-0.81 to 4.92) versus 5.02% (3.90 to 10.12), P=0.002. Twenty patients with PH underwent right heart catheterization: mean pulmonary artery pressure 38 (27-52) mm Hg, wedge capillary pressure 18 (16-22) mm Hg, pulmonary vascular resistance 362 (235-603) dyn s cm(-5). There was a significant inverse correlation between flow-mediated dilation and pulmonary vascular resistance in patients with HFpEF and PH (r=-0.679; P=0.002). Patients with HFpEF showed higher matrix metalloproteinase-2 and C-terminal propeptide of type I procollagen values than hypertensive controls. Patients with HFpEF and higher C-terminal propeptide of type I procollagen values also had higher mean pulmonary artery pressure (r=0.553; P=0.014), transpulmonary gradient (r=0.560; P=0.013), and pulmonary vascular resistance (r=0.626; P=0.004).
  
  
  CONCLUSIONS
  In patients with HFpEF, there is a significant correlation between PED and pulmonary vascular resistance. Collagen metabolism was more impaired in patients with HFpEF and PH. PED and collagen metabolism assessment could be useful tools to identify patients with HFpEF at risk of developing PH.
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain. mfarrero@clinic.ub.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Farrero
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Blanco
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Santiago
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cardona
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vidal
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Castel
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Sitges
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Barbera
authors.affiliation: From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Perez-Villa
mesh_terms: D000368:Aged; D001916:Brachial Artery / Q000503:physiopathology; D006328:Cardiac Catheterization; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000503:physiopathology*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011669:Pulmonary Wedge Pressure; D013318:Stroke Volume / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*; D014664:Vasodilation; D016278:Ventricular Function, Right / Q000502:physiology
keywords: pulmonary circulation; vascular resistance