Systemic Blood Pressure Is Associated with Anemia and Placenta Growth Factor In Sickle Cell Anemia

The seventh report of the Joint National Committee (JNC 7) defines hypertension as blood pressure (BP) ≥ 140/90 and pre-hypertension as BP ≥ 120/80. Data from the National Health and Nutrition Examination Survey (NHANES) shows that 42% of African American patients over the age of 20 are classified as hypertensive. Previous studies in patients with sickle cell disease (SCD) have reported that systemic blood pressures (BP) are lower than age- and race-matched controls. The purpose of this study was to evaluate the clinical and laboratory factors associated with systolic and diastolic blood pressures in SCD.

The data for this study was obtained from an ongoing study to determine the natural history of pulmonary hypertension in SCD. The first available systemic BP measurement for each patient was recorded, along with clinical and laboratory parameters. We evaluated associations between systolic and diastolic BP and 25 clinical and laboratory covariates using Spearman's correlation coefficient, and Wilcoxon Rank Sum tests for categorical covariates. Patients were stratified based on age and SCD genotype (SS, Sb⁰, SD vs. SC, Sb⁺). Blood pressures from our SCD patients were compared to median values obtained from the Cooperative Study of Sickle Cell Disease (CSSCD) using Wilcoxon Signed Rank tests.

Blood pressures were evaluated in 153 separate patients (SS = 115, SC = 18, Sb⁰ = 10, Sb⁺ = 9, SD =1), with a median age of 37 years (range 18 – 71 years). Thirty two (21%) patients had a known history of hypertension and 38 (25%) patients were on at least one antihypertensive medication for either hypertension or proteinuria. The mean (STD) systolic and diastolic BP for the patients with SS, Sb⁰ thalassemia, and SD (N=126) were 122 mm Hg (±15) and 69 mm Hg (±10), respectively; and the median systolic and diastolic BP for patients with SC and Sb⁺ thalassemia (N=27) were 131 mm Hg (±12) and 75 mm Hg (±13), respectively. We observed significant correlations between systolic BP and age (r=0.36, p=<.0001) and body mass index (BMI) (r=0.42, p=<.0001). We also observed significant correlations between SBP and hemoglobin (r=0.20, p=0.01); reticulocyte count (r=-0.29, p=0.0003); lactate dehydrogenase (r= −0.18, p=0.02); total bilirubin (r=−0.28, p=0.0008); indirect bilirubin (r=−0.28, p=0.001); white blood count (WBC) (r=−0.24, p=0.0023); absolute neutrophil count (r=−0.24, p=0.005); and placenta growth factor (PIGF) (r=−0.36, p=0.02). When compared to patients from the CSSCD, systolic BP was significantly higher in females ages 25–34 and 35–44, and in males ages 25–34 and 35–44 (Table 1).

The low systemic BP in SCD patients may be related to their lower BMI, combined with biologic factors such as anemia, hemolysis as well as increased levels of the vascular endothelial growth factor (VEGF) family member, placenta growth factor. The higher BP in our patient population compared to values in the CSSCD may be related to differences in BMI, degree of anemia, and levels of PlGF. With the increasing survival of SCD patients, studies are required to determine the appropriate BP levels to initiate anti-hypertensive therapy.

No relevant conflicts of interest to declare.