Cerebral Artery Pulsatility, Premorbid Blood Pressure, and Small Vessel Disease on Brain Imaging: A Population-Based...

Increased pulsatility of cerebral blood flow is proposed as a potential cause of cerebral small vessel disease (SVD), but the apparent association could be confounded by shared vascular risk factors, especially current and past blood pressure (BP). Most previous studies were small, usually in selected populations, and most did not adjust fully for confounders, particularly heart rate, pulse pressure, and premorbid BP. Therefore, we aimed to determine if cerebral pulsatility is independently associated with SVD on brain imaging.

Patients with TIA or minor ischemic stroke (NIH Stroke Scale ≤3) ascertained from 2011 to 2018 in a prospective population-based cohort study in Oxfordshire, the United Kingdom, were included. Cerebral pulsatility was measured with pulsatility index at the middle cerebral artery (MCA-PI) by transcranial Doppler ultrasound, and the burden of SVD was assessed using standard rating scales on MRI. We determined the associations of MCA-PI and SVD (total SVD score) adjusting for age, sex, vascular risk factors, heart rate, baseline BP (systolic, diastolic, and pulse pressure), and multiple premorbid BP readings up to 20 years before the event. We also performed mediation analysis to assess the contribution of MCA-PI on the causal pathway between BP and SVD.

Among 1,035 consecutive patients with measurements of both MCA-PI and SVD burden on MRI (mean age 66 years; 52.1% men), higher MCA-PI was associated with the total SVD score on MRI (top vs bottom quartile odds ratio [OR] 9.00, 95% CI 6.32-12.84). The association was attenuated after adjustment, but it remained significant (fully adjusted for systolic and diastolic BP OR 2.67, 1.55-4.60; for PP OR 1.88, 1.12-3.14). The results were consistent for individual markers of SVD (p-het = 0.77). In mediation analysis, 25.0% of the total association between premorbid systolic BP and SVD severity was due to MCA-PI.

In this cross-sectional analysis, cerebral pulsatility was positively associated with the increasing burden of cerebral SVD on brain MRI independent of age, sex, vascular risk factors, heart rate, baseline and premorbid BP in patients with TIA or minor ischemic stroke, and also explained a significant proportion of the association between BP and cerebral SVD on brain MRI. Prospective cohort studies and clinical trials targeting cerebral pulsatility are underway, which will help to further establish the role of cerebral pulsatility in SVD.