Blood pressure unknowns of sickle cell disease in children

Sickle Cell Disease (SCD) is a chronic genetic disorder due to a mutation in the β‐globin gene with resulting abnormal expression of hemoglobin S (Hb S). Homozygous Hb SS, with two copies of abnormal β‐globin chain, is associated with anemia, repeated ischemia‐reperfusion injury, and inflammation that can affect all organs, and can lead to acute chest syndrome, stroke, vasculopathy, and kidney disease. ¹ Hypertension is recognized and reported in adults with SCD where the abnormal blood pressure (BP) is commonly associated with pulmonary hypertension or chronic kidney disease. ² In children with SCD, clinic BP measurements are commonly normal or low. However, recent reports, in which investigators used 24‐hour ambulatory blood pressure monitoring (ABPM) to examine out‐of‐office BP, describe abnormal ambulatory BP patterns, in children with SCD. ³ , ⁴ , ⁵ Their findings of normal clinic BP with ambulatory hypertension are characteristic of masked hypertension. For example, in a sample of 52 children with SCD, Becker et al ³ identified masked hypertension in 35% of the patients and 56% lacked the normal nocturnal dip in BP. In 21% of the SCD children, microalbuminuria was present and their nocturnal BP dip was less than those without microalbuminuria.

The publication by Stabouli et al ⁶ in this issue of the Journal of Clinical Hypertension provides additional insights on abnormal BP in SCD. The investigators enrolled 16 pediatric patients with SCD and a comparator group of 16 pediatric patients who had been referred for suspicion of hypertension; thus, the comparator group was considered at high risk for hypertension. All participants had ABPM and also measurement of carotid‐femoral pulse wave velocity (cfPWV). Office hypertension was detected in 12.5% in SCD children compared to 43.8% of children at risk for hypertension. On ABPM 18.5% of SCD children had ambulatory hypertension compared to 25% among those with high risk for hypertension. Ambulatory hypertension in SCD children was consistently nocturnal hypertension. One child at risk for hypertension had both office and ambulatory hypertension resulting in 18.8% masked hypertension among the children at risk for hypertension. Therefore, the prevalence of masked hypertension appeared to be similar in the two groups. Interestingly, 25% of the SCD children had cfPWV > 95th % and 18.8% of the high risk for hypertension children had cfPWV > 95th%. Thus, prevalence of masked hypertension and elevated cfPWV was similar in the two groups. However, the underlying determinants of these hemodynamic and vascular phenotypes are quite different.

It is assumed that in this study the children considered at risk for hypertension did not have any underlying secondary cause of their abnormal BP, and they represented children at high risk for primary hypertension. Increased cfPWV, an estimate of vascular stiffness, has been reported in children with hypertension and with pre‐hypertension ⁷ and is thought to be indicative of hypertensive mediated target organ damage. Children with SCD already have a serious chronic disease, and the masked hypertension is most likely secondary to vascular consequences of SCD. Children with SCD typically have elevated glomerular filtration rate (GFR). With a later decline in GFR, albuminuria is commonly found. Patients with SCD are at high risk for developing chronic kidney disease in early adulthood, ⁸ and significant renal pathology has been documented in some children with SCD. ⁹ The exact mechanism for the nephropathic injury is currently not known. However, it is reported that angiotensin receptor blocker therapy for one year appeared to stabilize GFR and lower albumin excretion, suggesting potential benefits of early interventions on albuminuria. ¹⁰ The findings reported by Stabouli et al in this issue draws attention to abnormalities in BP and vascular stiffness in SCD. This publication and other recent reports indicate that clinical management of children with SCD should include screening for abnormal BP that includes out‐of‐office BP assessment. Further research is also needed to determine possible interventions that could mitigate the vascular and organ injury due to SCD that is already underway in childhood.

DISCLOSURES

None.

Falkner B. Blood pressure unknowns of sickle cell disease in children. J Clin Hypertens. 2020;22:1450–1451. 10.1111/jch.13971