title: NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease.
abstract: Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0·001), high lactate dehydrogenase (P<0·001), and high total bilirubin levels (P<0·007). A NT-proBNP level ≥160ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9-13·3, P<0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population.
authors.affiliation: Section of Pulmonary, Critical Care Medicine, Sleep and Allergy, University of Illinois at Chicago, Chicago, IL 60612, USA. machador@uic.edu
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.forename: Mariana
authors.initials: M
authors.lastname: Hildesheim
authors.forename: Laurel
authors.initials: L
authors.lastname: Mendelsohn
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D000328:Adult; D017677:Age Distribution; D000743:Anemia, Hemolytic / Q000209:etiology / Q000401:mortality; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000401:mortality; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain