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Differential impact of cumulative cerebral small-vessel disease burden on ischemic versus hemorrhagic stroke recurrence in hemorrhage-prone patients

Neurol Sci. 2026 May 22;47(6):511. doi: 10.1007/s10072-026-09105-1.

ABSTRACT

BACKGROUND: Total cerebral small-vessel disease (cSVD) score is a well-established predictor of vascular risks. However, the specific type of recurrent stroke associated with cSVD scores remains unclear in hemorrhage-prone patients-those with cerebral microbleeds (CMBs) or prior intracerebral hemorrhage (ICH).

METHODS: This study was a post hoc analysis of 1,454 patients enrolled in a prospective, multicenter, randomized controlled trial. Patients were categorized by modified cSVD (m-cSVD) scores 1-3. One point was awarded for each of the following: white matter hyperintensities (WMH) above the median, ≥2 CMBs or 1 ICH, and ≥1 lacune. The primary outcome was any stroke; secondary outcomes were ischemic and hemorrhagic stroke; the tertiary outcome was major adverse cardiovascular events (MACE). Multivariable Cox regression analysis was used to investigate associations between m-cSVD scores and events.

RESULTS: During a mean 1.9-year follow-up, the incidence rate per 100 person-years for ischemic stroke increased significantly with m-cSVD scores (1.9, 2.8, and 5.7, respectively). Compared to score 1, m-cSVD score 3 was associated with a higher risk of ischemic stroke (adjusted HR 2.72; 95% CI 1.03-7.18) and MACE (adjusted HR 2.34; 95% CI 1.08-5.10). While the incidence of hemorrhagic stroke showed a numerical increase (0.5, 0.8, and 1.5), this association did not reach statistical significance (unadjusted HR 3.05; 95% CI 0.66-14.14).

CONCLUSION: A high m-cSVD burden was independently associated with recurrent ischemic stroke, but not hemorrhagic stroke, in patients with high bleeding risk. High cSVD burden may reflects elevated ischemic risk, warranting careful consideration of ischemic stroke prevention even in patients with hemorrhagic potential.

PMID:42168664 | DOI:10.1007/s10072-026-09105-1

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