Risk factors for cerebral aneurysms in sickle cell disease

Specific risk factors for greater cerebral aneurysm frequency in sickle cell disease (SCD) compared to the general population have not been explored. In this cross-sectional, observational study, we hypothesize that increased cerebral blood flow (CBF), low hemoglobin (Hb) levels, and known risk factors for aneurysms in the general population are associated with aneurysms in SCD. From 2014 to 2022, in a single-center prospective cohort, children and young adults with SCD defined as HbSS and HbSβ0 thalassemia were recruited from an academic medical center clinic and a nearby community health clinic along with age and race-matched controls. Inclusion criteria were: ages 6–45 years, brain MRI and MRA, and risk factor data. CBF assessed via MRI with pseudo-continuous arterial spin labeling. Aneurysm prevalence was 13 of 183 (7.1%) SCD participants and 3 of 77 controls (3.9%). All aneurysms in control participants were found in women. In the SCD sample, 10 of 13 (76.9%) aneurysms occurred in males, while 76 of 170 (44.7%) without aneurysms were male ( p = 0.025); participants with aneurysms were older, 30.9 versus 17.2 years without aneurysm, ( p < 0.001). In the aneurysm group, 3 of 13 (23.1%) were smokers versus 8 of 170 (4.7%) without aneurysms, ( p = 0.035). Hb levels were not different in SCD participants with and without aneurysms, p = 0.358. CBF for the SCD group with aneurysms was 86.7 ± 25.9 ml/100 g/min compared to 80.8 ± 20.3 ml/100 g/min in the SCD group without aneurysms, ( p = 0.325). Using penalized logistic regression, in a model including age, sex, systolic blood pressure, and current smoking, only age (OR 1.14, 95% CI: 1.04– 1.24, p = 0.003) was significant; male sex (OR 3.85, 95% CI:0.86–17.16, p = 0.077) was not quite significant. In a second model including age, sex, and silent cerebral infarcts or ischemic stroke, only age (OR 1.14, 95% CI: 1.06– 1.24, p = 0.002) and male sex (OR 4.45, 95% CI:1.12–17.58, p = 0.033) were significant. In this observational study, increased CBF and low Hb levels were not linked to cerebral aneurysms in SCD. Age, smoking, and male sex were identified as risk factors for aneurysm development in SCD. Our findings are potentially clinically important for identifying higher risk subgroups for cerebral aneurysm in SCD.