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Published on: April 23, 2021
Impact of Cerebral Small Vessel Disease on Functional Decline: Bleeding With Antithrombotic Therapy 2 Study
Yoshito Arakaki1,2, Kaori Miwa1, Masatoshi Koga1
1Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (Y.A., K.M., M.K., S.Y., K. Tanaka, M. Shiozawa, K. Toyoda).
Insights
Cerebral small vessel disease (SVD) burden significantly contributes to functional decline in patients. This decline is linked to SVD severity, independent of major bleeding or ischemic events.
Area of Science:
- Neurology
- Vascular Neurology
- Neuroimaging
Background:
- Cerebral small vessel disease (SVD) is a common finding in the brain.
- The precise contribution of SVD to functional disability is not fully understood.
- Investigating the long-term impact of SVD on functional decline is crucial for patient care.
Purpose of the Study:
- To examine the longitudinal association between the burden of cerebral small vessel disease (SVD) and functional decline.
- To quantify the extent to which SVD contributes to disability progression over time.
Main Methods:
- Prospective, observational study of 4765 patients on oral antithrombotic therapy across 52 Japanese hospitals.
- SVD burden assessed using a 0-4 score on baseline MRI; functional decline measured by increase in modified Rankin Scale (mRS) score over 24 months.
- Logistic regression and causal mediation analyses evaluated the relationship between SVD score and functional decline, accounting for clinical factors and events.
Main Results:
- Higher SVD scores (≥3) were significantly associated with an increased risk of functional decline (ΔmRS score ≥1).
- Patients with SVD score 3 (aOR 1.65) and 4 (aOR 1.62) showed higher odds of functional decline compared to SVD score 0.
- Causal mediation analysis revealed that 73.05% of the effect of high SVD burden on functional decline was a direct effect, not mediated by bleeding or ischemic events.
Conclusions:
- Increased burden of cerebral small vessel disease (SVD) is a significant predictor of long-term functional decline.
- SVD's contribution to disability is substantial and occurs independently of major vascular events like bleeding or ischemia.
- These findings highlight the importance of managing SVD to prevent functional deterioration in at-risk populations.
Background:
To what extent cerebral small vessel disease (SVD) contributes to functional disability remains unclear. We investigated the longitudinal effect of SVD burden on functional decline.
Methods:
In this investigator-initiated, prospective, multicenter, and observational study, patients receiving oral antithrombotic therapy for cerebrovascular or cardiovascular diseases were enrolled from 52 hospitals across Japan (2016-2019) and followed for 24 months. SVD score (range, 0-4) was calculated on baseline magnetic resonance imaging obtained under prespecified conditions. The outcomes were an increase in modified Rankin Scale (mRS) score from baseline to end of follow-up (ΔmRS score ≥1). Logistic regression evaluated the association between ΔmRS score ≥1 and SVD score, adjusting for age, sex, premorbid mRS, vascular risk factors, antithrombotic therapy, magnetic resonance imaging field strength, and bleeding or ischemic events during follow-up. Bleeding and ischemic events were treated as time-dependent covariates. Causal mediation analyses using a 4-way decomposition separated the effects of SVD score ≥3 on ΔmRS score ≥1 into direct and indirect effects (mediated by major bleeding or ischemic events).
Results:
Of 5378 patients enrolled, 613 were excluded mainly due to the lack of clinical or imaging data. Finally, 4765 patients were analyzed (1573 women; median age, 73 years); ΔmRS score ≥1 was observed in 13.2% of patients with SVD score 0, 16.1% with 1, 20.7% with 2, 28.1% with 3, and 28.2% with 4. SVD score of 3 (adjusted odds ratio, 1.65 [95% CI, 1.27-2.15]) and SVD score of 4 (1.62 [95% CI, 1.19-2.19]) were associated with ΔmRS score ≥1 compared with SVD score of 0. Causal mediation analysis indicated that 73.05% of the total effect of SVD score ≥3 on ΔmRS score ≥1 was attributed to the controlled direct effect (coefficient, 0.497 [95% CI, 0.26-0.73]).
Conclusions:
SVD burden was associated with functional decline beyond significant bleeding or ischemic events.
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