Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease

Enrico M. Novelli, Mariana Hildesheim, Caterina Rosano, Rebecca Vanderpool, Marc Simon, Gregory J. Kato, Mark T. Gladwin

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Abstract

A seeming paradox of sickle cell disease is that patients do not suffer from a high prevalence of systemic hypertension in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, some patients do develop systolic hypertension and increased pulse pressure, an increasingly recognized major cardiovascular risk factor in other populations. Hence, we hypothesized that pulse pressure, unlike other blood pressure parameters, is independently associated with markers of hemolytic anemia and cardiovascular risk in sickle cell disease. We analyzed the correlates of pulse pressure in patients (n 5 661) enrolled in a multicenter international sickle cell trial. Markers of hemolysis were analyzed as independent variables and as a previously validated hemolytic index that includes multiple variables. We found that pulse pressure, not systolic, diastolic or mean arterial pressure, independently correlated with high reticulocyte count (beta 5 2.37, p 5 0.02) and high hemolytic index (beta 5 1.53, p50.002) in patients with homozygous sickle cell disease in two multiple linear regression models which include the markers of hemolysis as independent variables or the hemolytic index, respectively. Pulse pressure was also independently associated with elevated serum creatinine (beta 5 3.21, p 5 0.02), and with proteinuria (beta 5 2.52, p 5 0.04). These results from the largest sickle cell disease cohort to date since the Cooperative Study of Sickle Cell Disease show that pulse pressure is independently associated with hemolysis, proteinuria and chronic kidney disease. We propose that high pulse pressure may be a risk factor for clinical complications of vascular dysfunction in sickle cell disease. Longitudinal and mechanistic studies should be conducted to confirm these hypotheses.

Original languageEnglish (US)
Article numbere114309
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 5 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Novelli, E. M., Hildesheim, M., Rosano, C., Vanderpool, R., Simon, M., Kato, G. J., & Gladwin, M. T. (2014). Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease. PloS one, 9(12), [e114309]. https://doi.org/10.1371/journal.pone.0114309