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

Research output: Contribution to journalArticle

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
Externally publishedYes

Fingerprint

sickle cell anemia
hemolysis
Sickle Cell Anemia
Hemolysis
kidney diseases
Chronic Renal Insufficiency
Proteinuria
Blood Pressure
hypertension
Linear Models
risk factors
Hypertension
Reticulocyte Count
Blood pressure
reticulocytes
hemolytic anemia
proteinuria
Hemolytic Anemia
Linear regression
blood vessels

ASJC Scopus subject areas

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

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

Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease. / Novelli, Enrico M.; Hildesheim, Mariana; Rosano, Caterina; Vanderpool, Rebecca; Simon, Marc; Kato, Gregory J.; Gladwin, Mark T.

In: PLoS One, Vol. 9, No. 12, e114309, 05.12.2014.

Research output: Contribution to journalArticle

Novelli, EM, Hildesheim, M, Rosano, C, Vanderpool, R, Simon, M, Kato, GJ & Gladwin, MT 2014, 'Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease', PLoS One, vol. 9, no. 12, e114309. https://doi.org/10.1371/journal.pone.0114309
Novelli, Enrico M. ; Hildesheim, Mariana ; Rosano, Caterina ; Vanderpool, Rebecca ; Simon, Marc ; Kato, Gregory J. ; Gladwin, Mark T. / Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease. In: PLoS One. 2014 ; Vol. 9, No. 12.
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