Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria

Abstract

Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in subSaharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naïve Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity ≥2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were >35 years. Tricuspid regurgitant jet velocity was ≥2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin (P 5 0.002), blood urea nitrogen (P 5 0.019) and lactate dehydrogenase concentrations (P 5 0.026) and with inability to walk >300 m in 6 min (P 5 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations (P ≤ 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged. Am. J. Hematol. 83:485-490, 2008. V

A Novel Molecular Signature for Elevated Tricuspid Regurgitation Velocity in Sickle Cell Disease

“…This signature was found to be composed of both novel and established PH candidate genes as evidenced by literature mining and the PubMed search tool. For example, ADORA2B, a candidate gene known to modify the severity of SCD (20,21), was recently identified via metabolomic profiling of a transgenic SCD mouse model with excessive adenosine signaling through the ADORA2B leading to sickling and hemolysis (22), processes known to be independently correlated with the presence of PH in SCD (13,23). Furthermore, ADC, another signature gene, which decarboxylates L-arginine to agmatine, is an established PAH candidate gene (24) and is potentially involved in SCD-related PH (25).…”

Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease

“…Some studies have found an association of high hemoglobin F with lower pulmonary hypertension risk, [11][12][13][14] but several others have detected no such association. 1,2,[15][16][17][18] We recently reported a prospective, multicenter study of 310 children and adolescents with sickle cell disease at steady state in which tricuspid regurgitation velocity of 2.6 m/s or higher occurred in 11% of participants and had independent associations with hemolysis and hemoglobin oxygen desaturation. 3 In addition, we have found that an elevated screening tricuspid regurgitation velocity in children and adolescents with sickle cell disease predicts functional impairment over 2 years of follow-up (V.R.G., unpublished observations, April 2009).…”

Pulmonary Complications of Sickle Cell Disease

“…It is one of the most common monogenetic disorders in the world, affecting nearly 1 in 600 African Americans (3) and an estimated 1 to 4% of babies born in sub-Saharan Africa (4). The resulting hemolytic anemia is most severe in patients homozygous for the sickle hemoglobin (HbS) gene mutation (Hb-b; glu6val).…”