Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHLR200W mutation (Chuvash polycythemia)

Craig A. Sable, Zakari Y. Aliyu, Niti Dham, Mehdi Nouraie, Vandana Sachdev, Stanislav Sidenko, Galina Y. Miasnikova, Lydia A. Polyakova, Adelina I. Sergueeva, Daniel J. Okhotin, Vladimir Bushuev, Alan T. Remaley, Xiaomei Niu, Oswaldo L. Castro, Mark T. Gladwin, Gregory J. Kato, Josef T. Prchal, Victor R. Gordeuk

Research output: Contribution to journalArticlepeer-review


Background: Patients with Chuvash polycythemia, (homozygosity for the R200W mutation in the von Hippel Lindau gene (VHL)), have elevated levels of hypoxia inducible factors HIF-1 and HIF-2, often become iron-deficient secondary to phlebotomy, and have elevated estimated pulmonary artery pressure by echocardiography. The objectives of this study were to provide a comprehensive echocardiographic assessment of cardiovascular physiology and to identify clinical, hematologic and cardiovascular risk factors for elevation of tricuspid regurgitation velocity in children and adults with Chuvash polycythemia. Design and Methods: This cross-sectional observational study of 120 adult and pediatric VHLR200W homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation included echocardiography assessment of pulmonary artery pressure (tricuspid regurgitation velocity), cardiac volume, and systolic and diastolic function, as well as hematologic and clinical parameters. We determined the prevalence and risk factors for elevation of tricuspid regurgitation velocity in this population and its relationship to phlebotomy. Results: The age-adjusted mean ± SE tricuspid regurgitation velocity was higher in VHLR200W homozy-gotes than controls with normal VHL alleles (2.5±0.03 vs. 2.3±0.05 m/sec, P=0.005). The age-adjusted left ventricular diastolic diameter (4.8±0.05 vs. 4.5±0.09 cm, P=0.005) and left atrial diameter (3.4±0.04 vs. 3.2±0.08 cm, P=0.011) were also greater in the VHLR200W homozygotes, consistent with increased blood volume, but the elevation in tricuspid regurgitation velocity persisted after adjustment for these variables. Among VHLR200W homozygotes, phlebotomy therapy was associated with lower serum ferritin concentration, and low ferritin independently predicted higher tricuspid regurgitation velocity (standardized beta=0.29; P=0.009). Conclusions: Children and adults with Chuvash polycythemia have higher estimated right ventricular systolic pressure, even after adjustment for echocardiography estimates of blood volume. Lower ferritin concentration, which is associated with phlebotomy, independently predicts higher tri-cuspid regurgitation velocity (www.clinicaltrials.gov identifier NCT00495638).

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
Issue number2
StatePublished - Feb 1 2012
Externally publishedYes


  • Ferritin
  • Hypoxia inducible factor
  • Pulmonary hypertension
  • Tricuspid regurgitation velocity
  • VHL

ASJC Scopus subject areas

  • Hematology


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