Abstract WP194: The Prevalence Of Intracranial Artery Stenosis And Ischemic Stroke In Familial Hypercholesterolemia: A Retrospective Cohort Study

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Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder, characterized by the early-onset elevation of LDL cholesterol (LDL-C) levels and premature coronary artery disease (CAD). Although the association between FH and CAD is well known, that between FH and cerebrovascular diseases including stroke and intracranial artery stenosis (ICAS) is still unclear. We hypothesized that long-standing excessive LDL-C levels in FH patients confer an increased risk of developing ICAS, and consequently FH patients are subject to ischemic stroke (IS). The aim of our study is to unveil the relationship between FH and cerebrovascular diseases including ICAS and IS. Methods: The associations of FH and high LDL-C with IS and ICAS were tested in neurologically normal subjects (NNS) who voluntarily underwent brain MRI from December 2000 to September 2011 at Health Science Center in Shimane, Japan, and FH patients who underwent brain MRI at National Cerebral and Cardiovascular Center in Japan from May 2005 to March 2020. The severity of ICAS was evaluated with MRA. Results: We enrolled 3181 NNS and 167 FH patients with the mean age of 62.3±0.2 and 61.5±1.3, respectively ( p = 0.10). There were 1159 females (46.2%) in NNS and 89 (53.3%) in FH patients ( p = 0.075). The prevalence of ICAS in the FH patients was significantly higher than in the NNS (5.7% vs. 37.1%, p < 0.001), and the incidence of IS was also higher in the FH patients (0.8% vs. 10.8%, p<0.001). Multiple regression analysis revealed that FH was an independent predictor for IS (OR 13.96, 95%CI 6.60-29.55, p < 0.001). Kaplan-Meier analysis showed a significant difference in the incidence of IS between the NNS and FH patients ( p < 0.001). Moreover, the presence of ICAS significantly associated with the incidence of IS in the FH patients (Cox regression analysis: HR 6.55, 95%CI 1.66-25.78, p = 0.007). Discussion: Our study demonstrated a significantly higher prevalence of ICAS in FH patients than control subjects with similar age. Moreover, ICAS conferred an increased risk of IS among the FH patients. These results may necessitate routine examinations of the brain as well as systemic arteries in FH patients. We conclude a positive relationship of FH with cerebrovascular diseases, including ICAS and IS.

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