Pathological correlates of brain arterial calcifications.

TitlePathological correlates of brain arterial calcifications.
Publication TypeJournal Article
Year of Publication2019
AuthorsShapiro, SD, Goldman, J, Morgello, S, Honig, L, Elkind, MSV, Marshall, RS, Mohr, JP, Gutierrez, J
JournalCardiovasc Pathol
Date Published2019 Jan - Feb
KeywordsAdult, Aged, Aged, 80 and over, Autopsy, Cholesterol, Circle of Willis, Cross-Sectional Studies, Female, Fibrosis, Humans, Intracranial Arteriosclerosis, Male, Middle Aged, Plaque, Atherosclerotic, Retrospective Studies, stroke, Vascular Calcification

BACKGROUND: In clinical practice, calcifications seen on computed tomographic studies within the large brain arteries are often referred to as a surrogate marker for cholesterol-mediated atherosclerosis. However, limited data exist to support the association between calcification and atherosclerosis. In this study, we examined if intracranial arterial calcifications were associated with cholesterol-mediated intracranial large artery atherosclerosis (ILAA) within the arteries of the circle of Willis in an autopsy-based sample.METHODS: We carried out a cross-sectional analysis of histopathological characteristics of brain large arteries obtained from autopsy cases. Brain large arteries were examined for evidences of calcifications, which were rated as macroscopic (coalescent) and microscopic (scattered). In addition to calcification, we also obtained measurement of the arterial wall and the presence of ILAA and nonatherosclerotic arterial fibrosis. We built hierarchical models adjusted for demographic and vascular risk factors to assess the relationship between calcification and ILAA.RESULTS: In univariate analysis, the presence of any arterial calcifications was associated with cerebral infarcts (29% vs. 14%, P<.01). Multivariate analysis revealed that among all calcifications, coalescent calcifications were not associated with ILAA. In contrast, scattered calcifications were associated with ILAA (P<.001), decreased lumen diameter (-1.87 +/- 0.41 mm, P≤.001), and increased luminal stenosis (0.03% +/- 0.01%, P≤.006). These findings were independent of age, sex, or other vascular risk factors.CONCLUSIONS: This study demonstrates that coalescent calcifications in brain large arteries, although associated with morbidity, are not synonymous with cholesterol-driven ILAA. Understanding the precise pathological components of cerebrovascular disease, including nonatherosclerotic arterial calcifications, will help develop individualized therapies beyond amelioration of traditional risk factors such as hyperlipidemia.

Alternate JournalCardiovasc Pathol
PubMed ID30399527
PubMed Central IDPMC6294705
Grant ListR01 MH064168 / MH / NIMH NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
HHSN271201300028C / MH / NIMH NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
R25 MH080663 / MH / NIMH NIH HHS / United States
R01 AG057709 / AG / NIA NIH HHS / United States