ALBERT

Description: Pulmonary hypertension has a prevalence of 30% in patients with sickle cell disease (SCD) in the United States with mortality rates of 40% at 40 months after diagnosis. The global burden of SCD is highest in sub-Saharan Africa where more than 200,000 children are born with the disease annually. The prevalence of pulmonary hypertension among individuals with SCD in Africa has not been previously reported. We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 206 consecutive hydroxyurea sickle cell patients at steady state in Nigeria, West Africa (101 males and 105 females; age range 10–52, mean [+/−SD] age, 21.5 +/− 7.7 years; 196 homozygous sickle cell and 10 compound heterozygotes SC). A control group consisted of 93 healthy Nigerians. Hemoglobin gentotype was determined by electrophoresis and DNA sequencing. Pulmonary hypertension was defined prospectively as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m per second. We collected clinical data on the patients and controls, and blood specimens for clinical laboratory measurements. Doppler-defined pulmonary hypertension occurred in 25% of sickle cell patients (21% with TRV 2.5 – 2.9 m/sec, 4% with TRV ≥ 3 m/sec). The presence of pulmonary hypertension was inversly associated with age (p=0.04) and hemoglobin (p=0.0016), and positively associated with reticulocyte count, serum levels of lactose dehydrogenase (p=0.03), creatine kinase, and blood urea nitrogen and systolic (p=0.03) and diastolic blood pressure (p=0.002) in bivariate analyses. In a multivariate linear regression model age, diastolic blood pressure and blood urea nitrogen had significant independent associations with pulmonary hypertension. There were no significant associations of HIV/AIDS, hepatitis B and C co infections and malarial parasitemia rate with pulmonary hypertension. Our findings suggest that pulmonary hypertension is common among sickle cell patients in Africa and it appears to be a complication of chronic hemolysis and vasculopathy. The prevalence of pulmonary hypertension decreases with age in Nigerian SCD patients, in sharp contrast to U.S. SCD patients, who demonstrate increasing prevalence with age. The public health implications of this finding are significant considering the potential number of individuals at risk for this complication. Large prospective cohort studies to determine the outcome of pulmonary hypertension in sickle cell patients in Africa are needed.