日本人の家族性高コレステロール血症が、脳梗塞のリスクに~アジアでの国際共同研究構築への基盤データに~

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2026-02-16 国立循環器病研究センター

国立循環器病研究センターの研究で、日本人の家族性高コレステロール血症(FH)が脳梗塞や頭蓋内動脈狭窄症の独立したリスクであることが明らかになった。FHは出生時からLDLコレステロールが高い遺伝性疾患で、これまで冠動脈疾患との関連が中心に研究されてきたが、今回の解析ではFH患者で脳梗塞発症率が明確に高く、さらに頭蓋内動脈狭窄症の有病率も高いことが示された。これらは欧州の報告とは異なり、日本人・アジア人特有の脳血管病リスクを示唆する結果となった。FH患者に対しては、冠動脈疾患のみならず脳卒中や認知症予防を視野に入れた診療や脳MRIによる評価、他の危険因子管理の重要性が指摘されている。現在、アジア全体での国際共同研究の構築も進められている。

<関連情報>

家族性高コレステロール血症における虚血性脳卒中および頭蓋内大動脈疾患リスク:日本における前向き研究 Ischemic stroke and intracranial large-artery disease risk in familial hypercholesterolemia: A prospective Japanese study

Yorito Hattori ∙ Kotaro Noda ∙ Mika Hori ∙ … ∙ Shuhei Yamaguchi ∙ Mariko Harada-Shiba ∙ Masafumi Ihara
Atherosclerosis  Published:February 11, 2026
DOI:https://doi.org/10.1016/j.atherosclerosis.2026.120674

Highlights

  • Familial hypercholesterolemia (FH) was a significant risk of intracranial large-artery disease in the Japanese population.
  • FH was an independent risk for high incidence of ischemic stroke in the Japanese population.
  • Intracranial large-artery disease was an independent risk factor for ischemic stroke in Japanese patients with FH.
  • These findings highlight the importance of considering ethnic and genetic differences in stroke prevention strategies.
  • Appropriate management of FH should be central to precision medicine approaches for reducing burden of stroke in Japan.

Abstract

Background and aims

The contribution of dyslipidemia to stroke risk is generally considered weaker than that of hypertension and diabetes. However, some previous studies suggest that dyslipidemia is associated with intracranial major artery stenosis (ICAS) and ischemic stroke, particularly in Asians populations, who are more susceptible to ICAS than Caucasians. We hypothesized that dyslipidemia, and specifically familial hypercholesterolemia (FH), may play a different role in the development of stroke in Asian populations. This study aimed to assess the prevalence and incidence of symptomatic ischemic stroke and ICAS in Japanese patients with FH compared to individuals undergoing Brain Dock.

Methods

This prospective longitudinal study included FH patients who visited a lipid clinic and underwent brain magnetic resonance imaging (MRI) at the National Cerebral and Cardiovascular Center, alongside participants who underwent brain MRI as part of the Brain Dock screening program in Japan.

Results

In total, 3178 participants who underwent Brain Dock and 150 patients with FH were included. FH was an independent risk factor of a higher prevalence of ICAS (≥50%; adjusted odds ratio: 17.82, 95% confidence interval [CI]: 8.74–36.36), and high symptomatic ischemic stroke incidence (adjusted hazard ratio [aHR]: 5.83, 95% CI: 2.03–16.77). The presence of ICAS was significantly associated with symptomatic ischemic stroke in patients with FH (aHR: 7.73, 95% CI: 1.53–39.06).

Conclusions

FH may confer a high risk for symptomatic ischemic stroke along with intracranial major artery changes in Japanese patients. These findings highlight the importance of considering ethnic and genetic differences in stroke prevention strategies.

医療・健康
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