Familial Hypercholesterolemia, as an Independent Risk of Cerebral Small Vessel Disease

Familial hypercholesterolemia (FH) is characterized by elevated levels of LDL-C (low-density lipoprotein cholesterol) since birth. However, the association between FH and cerebrovascular diseases, including cerebral small vessel disease (CSVD), is controversial. To investigate the association between FH and CSVD, we compared the prevalence and severity of CSVD neuroradiological findings between patients with FH and control participants.

Patients with FH who visited the lipid clinic and underwent brain magnetic resonance imaging at the National Cerebral and Cardiovascular Center in Japan from November 2006 to April 2021 and control participants who voluntarily underwent brain magnetic resonance imaging as a checkup between December 2000 and December 2010 at the Health Science Center Shimane, Japan, were enrolled into the study. The prevalence and severity of CSVD neuroradiological findings were investigated in patients with FH and control participants, and potential risk factors for CSVD development were identified using multivariable logistic and quasi-Poisson regression analyses.

A total of 151 patients with FH and 3172 control participants were enrolled in this study. FH was identified as an independent risk factor of prevalent lacunes (adjusted odds ratio, 1.60 [95% CI, 1.03-2.51]; P=0.039) and increased number of lacunes (1.67 times [95% CI, 1.17-2.31]; P=0.003). Furthermore, FH was also an independent risk factor of prevalent cerebral microbleeds (adjusted odds ratio, 9.42 [95% CI, 5.81-15.28]; P<0.001) and increased number of cerebral microbleeds (6.95 times [95% CI, 4.34-10.83]; P<0.001).

The association of FH with lacunes and cerebral microbleeds may warrant routine brain imaging for primary prevention of symptomatic stroke in patients with FH.