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

PLoS One. 2014 Dec 5;9(12):e114309. doi: 10.1371/journal.pone.0114309. eCollection 2014.

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 = 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 = 2.37, p = 0.02) and high hemolytic index (beta = 1.53, p = 0.002) 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 = 3.21, p = 0.02), and with proteinuria (beta = 2.52, p = 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell* / blood
  • Anemia, Sickle Cell* / complications
  • Anemia, Sickle Cell* / physiopathology
  • Biomarkers / blood
  • Blood Pressure*
  • Child
  • Female
  • Hemolysis*
  • Humans
  • Male
  • Middle Aged
  • Proteinuria* / blood
  • Proteinuria* / etiology
  • Proteinuria* / physiopathology
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / etiology
  • Renal Insufficiency, Chronic* / physiopathology

Substances

  • Biomarkers

Grants and funding

EMN, MH, RV, MS, GJK and MTG are supported by the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.