Research Article| Volume 371, P14-20, April 2023

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Differential association between apolipoprotein B and LDL cholesterol and cerebral atherosclerosis according to pre-stroke statin use

  • Minyoul Baik
    Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea

    Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, South Korea
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  • Hyo Suk Nam
    Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea

    Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, South Korea
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  • Ji Hoe Heo
    Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea

    Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, South Korea
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  • Hye Sun Lee
    Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, South Korea
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  • Young Dae Kim
    Corresponding author. Integrative Research Center for Cerebrovascular and Cardiovascular diseases, Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
    Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea

    Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, South Korea
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      • LDL-C and ApoB are associated with atherosclerotic stenosis in stroke patients.
      • ApoB was consistently associated with intracranial stenosis regardless of statin use.
      • LDL-C was associated with atherosclerosis only in statin-naïve patients.
      • This differential effect may partially explain the residual risk in statin use.
      • Lipid-lowering therapy targeting not only LDL-C, but also ApoB, is needed.


      Background and aims

      To reduce cardiovascular risk, low-density lipoprotein cholesterol (LDL-C) is the primary target of statin treatment, while apolipoprotein B (ApoB) is secondary. We investigated the association between atherosclerotic stenosis and LDL-C or ApoB levels and whether a difference in association exists according to pre-admission statin use in ischemic stroke patients.


      This retrospective cross-sectional study included consecutive patients with acute ischemic stroke or transient ischemic attack who underwent lipid profile and angiographic testing. Patients were categorized into four groups according to stenosis location: normal, extracranial atherosclerotic stenosis (ECAS), intracranial atherosclerotic stenosis (ICAS), or ECAS + ICAS. Subgroup analyses were performed by pre-admission statin use.


      Of the 6338 patients included, 1980 (31.2%) were in the normal group, 718 (11.3%) in the ECAS group, 1845 (29.1%) in the ICAS group, and 1795 (28.3%) in the ECAS + ICAS group. Both LDL-C and ApoB levels were associated with every location of stenosis. A significant interaction was found between pre-admission statin use and LDL-C level (p for interaction <0.05). LDL-C was associated with stenosis only in statin-naïve patients, whereas ApoB was associated with ICAS, with or without ECAS, in both statin-naïve and statin-treated patients. ApoB also showed a consistent association with symptomatic ICAS in both statin-treated and statin-naïve patients, whereas LDL-C did not.


      ApoB was consistently associated with ICAS, particularly symptomatic stenosis, in both statin-naïve and statin-treated patients. The close association between ApoB levels and residual risk in statin-treated patients could be partially explained by these results.

      Graphical abstract


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