Abstract

BACKGROUND

Cerebral small vessel disease (cSVD) is a major contributing factor to ischemic stroke and dementia. However, the vascular pathologies of cSVD remain inconclusive. The aim of this systematic review and meta-analysis was to characterize the associations between cSVD and cerebrovascular reactivity (CVR), cerebral autoregulation, and arterial stiffness (AS).

METHODS AND RESULTS

MEDLINE, Web of Science, and Embase were searched from inception to September 2023 for studies reporting CVR, cerebral autoregulation, or AS in relation to radiological markers of cSVD. Data were extracted in predefined tables, reviewed, and meta-analyses performed using inverse-variance random effects models to determine pooled odds ratios (ORs). A total of 1611 studies were identified; 142 were included in the systematic review, of which 60 had data available for meta-analyses. Systematic review revealed that CVR, cerebral autoregulation, and AS were consistently associated with cSVD (80.4%, 78.6%, and 85.4% of studies, respectively). Meta-analysis in 7 studies (536 participants, 32.9% women) revealed a borderline association between impaired CVR and cSVD (OR, 2.26 [95% CI, 0.99-5.14]; =0.05). In 37 studies (27 952 participants, 53.0% women) increased AS, per SD, was associated with cSVD (OR, 1.24 [95% CI, 1.15-1.33]; <0.01). Meta-regression adjusted for comorbidities accounted for one-third of the AS model variance (=29.4%, =0.02). Subgroup analysis of AS studies demonstrated an association with white matter hyperintensities (OR, 1.42 [95% CI, 1.18-1.70]; <0.01).

CONCLUSIONS

The collective findings of the present systematic review and meta-analyses suggest an association between cSVD and impaired CVR and elevated AS. However, longitudinal investigations into vascular stiffness and regulatory function as possible risk factors for cSVD remain warranted.

MeSH

Heart Diseases, Homeostasis, Cerebral Small Vessel Diseases

Cited by

• External Validation of the American Heart Association PREVENT Cardiovascular Disease Risk Equations. JAMA Netw Open, 2024
• Arterial stiffness moderates the link between NfL and cognition: The IGNITE study. Alzheimers Dement, 2025
• Imaging-validated correlates and implications of the pathophysiologic mechanisms of ageing-related cerebral large artery and small vessel diseases: a systematic review and meta-analysis. Behav Brain Funct, 2025
• Different implications of daytime and nighttime heart rate variability on total burden of cerebral small vascular disease in patients with nondisabling ischemic cerebrovascular events. Front Cardiovasc Med, 2024
• Impact of white matter lesions on associations between prehospital blood pressure and outcomes in spontaneous intracerebral hemorrhage. Eur Stroke J, 2025
• CD8 + T-cell metabolism is related to cerebrovascular reactivity in middle-aged adults. Am J Physiol Regul Integr Comp Physiol, 2024
• Retinal vascular reactivity is associated with white matter hyperintensities and dysfunctional cerebrovascular reactivity in cerebral small vessel disease. J Cereb Blood Flow Metab, 2025