Chronobiology of Hypertension in Sickle Cell Disease

Introduction: Adult patients with Sickle Cell Disease (SCD): 1) develop renal failure at an earlier age than non-SCD black patients with end stage renal disease and 2) renal transplant outcomes in patients with SCD are so inferior that many transplant programs will not consider patients with SCD as candidates. More research is needed to understand the development of renal disease in patients with SCD; particularly in the earlier stages in which interventions might be most successful. In non-SCD pediatric populations, 24 hour Ambulatory Blood Pressure Monitoring (ABPM) is the gold standard method to document hypertension as it has been shown to be a better surrogate outcome for end organ damage from hypertension. The association between hypertension (as defined by ABPM) and progressive kidney disease needs to be assessed in SCD.

Objective: To identify baseline blood pressure (BP) abnormalities as measured by ABPM and conventional clinic measurement and to characterize factors associated with ABPM abnormalities among a cohort of sickle cell participants enrolled in a 5 year prospective study of hypertension and progressive kidney injury.

Methods: Participants ages 5-21 yrs with HbSS or SB0 thalassemia were enrolled in a five year IRB approved prospective cohort study; participants 11-20 yrs were also eligible to undergo 24 hr ABPM. Demographics, therapies,and laboratory data (CBC, CMP, uric acid, LDH, cystatin c, and urine microalbumin/creatinine) were recorded. The pre-transfusion CBC was used for patients on chronic transfusion therapy. Clinic BP and 24 hr ABPM (using SpaceLabs 90217 monitors which records BP every 20 minutes while awake and 30 minutes while asleep for at least 24 hours) were measured. BP level norms were determined by pediatric BP tables created by the NHLBI (clinic BP) and American Heart Association (ABPM) for age and height. Abnormal nocturnal dipping is defined as <10% BP dip (daytime-nighttime BP)/daytime BP x 100). Abnormal BP load is defined as > 25% of blood pressure recordings exceeding the 95^th percentile BP for normative data.

Results: At the time of this abstract, 29/108 (27%) of participants were hypertensive at their baseline clinic visit and 24-hr ABPM has been conducted in 27 participants (7 were normotensive in clinic; 20 were normotensive during clinic visit). Twenty two of the 27 (81%) participants were identified with abnormal systolic nocturnal BP dipping and 15/27 (56%) had abnormal diastolic nocturnal BP dipping. Of concern, 10/27 (37%) participants had an increase in SBP while sleeping and 7/27 (26%) had an increase in DBP while sleeping. Among the seven participants with hypertension in clinic, all had abnormal nocturnal BP dipping. In those participants with normal clinic BP, 15/20 (75%) had abnormal systolic BP dipping. Nine (33%) participants had an abnormal nocturnal systolic BP load and 7 (26%) participants had abnormal nocturnal diastolic BP load. Eight of 10 participants with an increase in systolic BP while sleeping were on chronic transfusion therapy (p=0.06). Variables that may be associated with an increase in systolic BP while sleeping were: lower GFR (p=0.06), higher BMI (p=0.02), and higher hemoglobin (p=0.08). Participants on chronic transfusion had a higher mean nocturnal systolic BP load than participants on no chronic therapy or hydroxyurea therapy (p=0.04). Variables that may be associated with an abnormal nocturnal systolic BP load were: lower GFR (p<0.001), higher BMI (p=0.01), and higher Hb (p=0.01). Transfusion volume (mL) was not associated with abnormal dipping (p=0.72) or BP load (p=0.52).

Conclusion: Abnormal nocturnal BP is highly prevalent among SCD participants with and without hypertension in clinic. Blood therapy or need for blood therapy may be associated with abnormal nocturnal BP. Participants with abnormal nocturnal BP may have a lower GFR. Over time, this cohort will determine if abnormal nocturnal BP predicts a progressive decline in GFR in SCD as it does in non-SCD populations.