Sex-Specific Associations of Carotid Plaque Calcification Subtypes with Stroke, TIA, and Retinal Ischemia

Abstract

BackgroundCalcification in carotid plaques has been suggested to represent a stabilizing plaque feature, but previous findings are conflicting. Whether histologically defined calcification subtypes are associated with distinct cerebrovascular event phenotypes and whether these associations differ by sex remain unclear.

MethodsIn this prospective Helsinki Carotid Endarterectomy Study 2, carotid plaques from 483 patients (328 men) undergoing carotid endarterectomy were analyzed histologically using AI-based quantification of sheet, nodular, and total calcification (%). Calcification measures were compared with patient characteristics, plaque morphology, CTA-based calcium score, and neurological symptom subtypes (asymptomatic (n=167), stroke (n=132), transient ischemic attack (TIA) (n=79), retinal infarction (n=24), and amaurosis fugax (n=81)), with sex-stratified analyses.

ResultsWomen had more plaque calcification than men (median total calcification, 15.8% versus 10.8%; p=0.002). In the overall cohort, symptomatic plaques showed lower total and sheet calcification than asymptomatic plaques, an association driven by men. Among male patients, stroke-associated plaques had less sheet calcification than asymptomatic plaques (median, 3.4% versus 8.4%; p<0.001). In women, plaques associated with TIA showed higher total calcification than stroke-associated plaques (median, 22.7% versus 13.5%; p=0.024). Retinal infarction was associated with higher nodular calcification than stroke in the overall cohort (median, 9.6% versus 1.2%; p=0.004). Histological total calcification correlated with CTA-based calcium score (p<0.001), and radiological calcification showed corresponding associations with neurological symptom type.

ConclusionsOverall, symptomatic plaques showed lower total and sheet calcification than asymptomatic plaques. In men, low total and sheet calcification were associated with stroke, whereas higher nodular calcification was associated with retinal infarction. In women, high total calcification was associated with TIA. These findings suggest that although calcification appears to be a stabilization plaque feature, its clinical implications depend on its morphological subtype and vary according to sex and neurological symptom subtype.

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BibTeX RIS

BibTeX

@misc{komi2026sexspecific,
  title = {{Sex-Specific Associations of Carotid Plaque Calcification Subtypes with Stroke, TIA, and Retinal Ischemia}},
  author = {H. J. Komi and P. H. Ijäs and K. Nuotio and L. Mäkitie and M. I. Mäyränpää and M. Shoghli and R. Tulamo and P. J. Vikatmaa and P. J. Lindsberg and L. Soinne and S. M. Koskinen and J. Sinisalo and A. I. Lokki},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.14.26363078},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.14.26363078v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - Sex-Specific Associations of Carotid Plaque Calcification Subtypes with Stroke, TIA, and Retinal Ischemia
AU  - H. J. Komi
AU  - P. H. Ijäs
AU  - K. Nuotio
AU  - L. Mäkitie
AU  - M. I. Mäyränpää
AU  - M. Shoghli
AU  - R. Tulamo
AU  - P. J. Vikatmaa
AU  - P. J. Lindsberg
AU  - L. Soinne
AU  - S. M. Koskinen
AU  - J. Sinisalo
AU  - A. I. Lokki
PY  - 2026
DA  - 2026/09/14
PB  - medRxiv
DO  - 10.64898/2026.09.14.26363078
UR  - https://www.medrxiv.org/content/10.64898/2026.09.14.26363078v1
AB  - BackgroundCalcification in carotid plaques has been suggested to represent a stabilizing plaque feature, but previous findings are conflicting. Whether histologically defined calcification subtypes are associated with distinct cerebrovascular event phenotypes and whether these associations differ by sex remain unclear.  MethodsIn this prospective Helsinki Carotid Endarterectomy Study 2, carotid plaques from 483 patients (328 men) undergoing carotid endarterectomy were analyzed histologically using AI-based quantification of sheet, nodular, and total calcification (%). Calcification measures were compared with patient characteristics, plaque morphology, CTA-based calcium score, and neurological symptom subtypes (asymptomatic (n=167), stroke (n=132), transient ischemic attack (TIA) (n=79), retinal infarction (n=24), and amaurosis fugax (n=81)), with sex-stratified analyses.  ResultsWomen had more plaque calcification than men (median total calcification, 15.8% versus 10.8%; p=0.002). In the overall cohort, symptomatic plaques showed lower total and sheet calcification than asymptomatic plaques, an association driven by men. Among male patients, stroke-associated plaques had less sheet calcification than asymptomatic plaques (median, 3.4% versus 8.4%; p<0.001). In women, plaques associated with TIA showed higher total calcification than stroke-associated plaques (median, 22.7% versus 13.5%; p=0.024). Retinal infarction was associated with higher nodular calcification than stroke in the overall cohort (median, 9.6% versus 1.2%; p=0.004). Histological total calcification correlated with CTA-based calcium score (p<0.001), and radiological calcification showed corresponding associations with neurological symptom type.  ConclusionsOverall, symptomatic plaques showed lower total and sheet calcification than asymptomatic plaques. In men, low total and sheet calcification were associated with stroke, whereas higher nodular calcification was associated with retinal infarction. In women, high total calcification was associated with TIA. These findings suggest that although calcification appears to be a stabilization plaque feature, its clinical implications depend on its morphological subtype and vary according to sex and neurological symptom subtype.
ER  -

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