Rate of, and risk factors for, white matter hyperintensity growth: a systematic review and meta-analysis with
Robin Brown1, Audrey Low2, Hugh S Markus3
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK rbb29@cam.ac.uk.
Background:
White matter hyperintensities (WMHs) are a highly prevalent MRI marker of cerebral small vessel disease (SVD), which predict stroke and dementia risk, and are being increasingly used as a surrogate marker in clinical trials. However, the influence of study population selection on WMH progression rate has not been studied and the effect of individual patient factors for WMH growth are not fully understood.
Methods:
We performed a systematic review and meta-analysis of the literature on progression of WMHs in longitudinal studies to determine rates of WMH growth, and how these varied according to population characteristics and cardiovascular risk factors. We used these data to calculate necessary sample sizes for clinical trials using WMH as an endpoint.
Results:
WMH growth rate was highest in SVD (2.50cc/year), intermediate in unselected stroke patients (1.29cc/year) and lower in patients with non-stroke cardiovascular disease, and with cognitive impairment. Age was significantly associated with progression (correlation coefficient 0.15cc/year, 95% CI 0.02 to 0.28cc/year) as was baseline lesion volume (0.6cc/year, 95% CI 0.13 to 1.06 cc/year). Both hypertension (OR 1.72, 95% CI 1.19 to 2.46) and current smoking (OR 1.48, 95% CI 1.02 to 2.16) were associated with WMH growth. Sample sizes for a clinical trial varied greatly with patient population selection and baseline lesion volume; estimates are provided.
Conclusions:
WMH progression varies markedly according to the characteristics of the population being studied and this will have a major impact on sample sizes required in a clinical trial. Our sample size estimates provide data for planning clinical trials using WMH as an outcome measure.
Prospero Registration Number:
CRD42020191781.
Insights
White matter hyperintensities (WMH) progression varies significantly based on patient selection and risk factors. Understanding these factors is crucial for accurately estimating sample sizes in clinical trials for cerebral small vessel disease.
Area of Science:
- Neurology
- Radiology
- Clinical Trials
Background:
- White matter hyperintensities (WMHs) are key MRI markers for cerebral small vessel disease (SVD).
- WMHs predict stroke and dementia risk and are used as surrogate markers in clinical trials.
- Factors influencing WMH progression and population selection effects on progression rates are not fully understood.
Purpose of the Study:
- To systematically review and meta-analyze WMH progression in longitudinal studies.
- To determine WMH growth rates and their variation by population characteristics and cardiovascular risk factors.
- To calculate necessary sample sizes for clinical trials using WMH as an endpoint.
Main Methods:
- Systematic review and meta-analysis of longitudinal studies on WMH progression.
- Analysis of WMH growth rates across different patient populations.
- Statistical analysis to identify factors associated with WMH progression.
Main Results:
- WMH growth rates varied: highest in SVD (2.50cc/year), intermediate in stroke patients (1.29cc/year), and lower in other groups.
- Age and baseline lesion volume were significantly associated with WMH progression.
- Hypertension and current smoking were linked to increased WMH growth.
Conclusions:
- WMH progression rates differ significantly based on study population characteristics.
- These variations critically impact sample size calculations for clinical trials.
- Provided sample size estimates aid in planning trials utilizing WMH as an outcome measure.
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