title: Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom.
abstract: BACKGROUND
  The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.
  
  
  RESULTS
  We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥ 3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥ 25 mm Hg was used. Among 572 subjects, 11.2% had TRV ≥ 3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥ 160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV ≥ 3.0 m/sec. At 24 months the cumulative survival was 83% with TRV ≥ 3.0 m/sec and 98% with TRV < 3.0 m/sec (p < 0.0001). The hazard ratios for death were 11.1 (95% CI 4.1-30.1; p < 0.0001) for TRV ≥ 3.0 m/sec, 4.6 (1.8-11.3; p = 0.001) for NT-proBNP ≥ 160 pg/mL, and 14.9 (5.5-39.9; p < 0.0001) for both TRV ≥ 3.0 m/sec and NT-proBNP ≥ 160 pg/mL. Age > 47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.
  
  
  CONCLUSIONS
  A TRV ≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531.
authors.affiliation: Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.affiliation: Columbia University, New York, New York, United States of America.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.affiliation: National Heart & Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: J Simon R
authors.initials: JS
authors.lastname: Gibbs
authors.affiliation: Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Mariana
authors.initials: M
authors.lastname: Hildesheim
authors.affiliation: Cardiovascular Branch, NHLBI, Bethesda, Maryland, United States of America.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.affiliation: Howard University, Washington, DC, United States of America.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.affiliation: University of Colorado HSC, Denver, Colorado, United States of America.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Hassell
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Little
authors.affiliation: University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Dean E
authors.initials: DE
authors.lastname: Schraufnagel
authors.affiliation: Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Krishnamurti
authors.affiliation: Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Enrico
authors.initials: E
authors.lastname: Novelli
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Reda E
authors.initials: RE
authors.lastname: Girgis
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Morris
authors.affiliation: Columbia University, New York, New York, United States of America.
authors.forename: Erika
authors.initials: E
authors.lastname: Berman Rosenzweig
authors.affiliation: University of Colorado HSC, Denver, Colorado, United States of America.
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanzkron
authors.affiliation: Howard University, Washington, DC, United States of America.
authors.forename: Oswaldo L
authors.initials: OL
authors.lastname: Castro
authors.affiliation: Cardiovascular Branch, NHLBI, Bethesda, Maryland, United States of America.
authors.forename: James G
authors.initials: JG
authors.lastname: Taylor
authors.affiliation: National Heart Lung and Blood Institute/NIH, Bethesda, Maryland, United States of America.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Goldsmith
authors.affiliation: Cardiovascular Branch, NHLBI, Bethesda, Maryland, United States of America.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.affiliation: University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.affiliation: University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000401:mortality / Q000473:pathology*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D005293:Ferritins / Q000032:analysis; D005500:Follow-Up Studies; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D006113:United Kingdom; D014481:United States; D016138:Walking
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D005293:Ferritins; D003404:Creatinine