Neurovascular Coupling Is Impaired in Hypertensive and Diabetic Subjects Without Symptomatic Cerebrovascular Disease.

Ana Monteiro,Jorge Polónia,Farzaneh Sorond,James P Higgins,Gilberto Pereira,Carmen Ferreira,Elsa Azevedo,Pedro Castro,Andrew Milstead

doi:10.3389/fnagi.2021.728007

Abstract

The mechanistic link between hypertension, diabetes and cerebral small vessel disease (CSVD) is still poorly understood. We hypothesized that hypertension and diabetes could impair cerebrovascular regulation prior to irreversibly established cerebrovascular disease. In this study, 52 hypertensive patients [54% males; age 64 ± 11 years; 58% with comorbid diabetes mellitus (DM)] without symptomatic cerebrovascular disease underwent transcranial Doppler (TCD) monitoring in the middle (MCA) and posterior (PCA) cerebral arteries, to assess vasoreactivity to carbon dioxide (VRCO2) and neurovascular coupling (NVC). 1.5T magnetic resonance imaging was also performed and white matter hyperintensity volume was automatically segmented from FLAIR sequences. TCD data from 17 healthy controls were obtained for comparison (47% males; age 60 ± 16 years). Hypertensive patients showed significant impairment of NVC in the PCA, with reduced increment in cerebral blood flow velocity during visual stimulation (22.4 ± 9.2 vs. 31.6 ± 5.7, p < 0.001), as well as disturbed NVC time-varying properties, with slower response (lower rate time: 0.00 ± 0.02 vs. 0.03 ± 6.81, p = 0.001), and reduced system oscillation (reduced natural frequency: 0.18 ± 0.08 vs. 0.22 ± 0.06, p < 0.001), when compared to controls. VRCO2 remained relatively preserved in MCA and PCA. These results were worse in hypertensive diabetic patients, with lower natural frequency (p = 0.043) than non-diabetic patients. White matter disease burden did not predict worse NVC. These findings suggest that hypertensive diabetic patients may have a precocious impairment of NVC, already occurring without symptomatic CSVD. Future research is warranted to evaluate whether NVC assessment could be useful as an early, non-invasive, surrogate marker for CSVD.

Highlights

Cerebral small vessel disease (CSVD) has an enormous impact on public health worldwide (GBD 2017 Causes of Death Collaborators, 2018)
Our study shows that neurovascular coupling (NVC) was significantly impaired in hypertensive patients, with reduced Cerebral blood flow velocity (CBFV) increase and altered time behavior hemodynamic evoked response during visual stimulation
The novel finding is that the natural frequency seems to be the most sensitive parameter for discriminating abnormal NVC in these patients

Summary

Introduction

Cerebral small vessel disease (CSVD) has an enormous impact on public health worldwide (GBD 2017 Causes of Death Collaborators, 2018). It accounts for 25% of ischemic strokes and most hemorrhagic strokes and is the second leading cause for cognitive decline (Sudlow and Warlow, 1997; Iadecola et al, 2019). Many of its manifestations are clinically silent until the development of clinical consequences, with stroke, cognitive decline, and gait impairment, limiting disease-specific preventive strategies (Pantoni, 2010). CSVD radiological markers and clinical manifestations seem to be dissociated, for reasons not fully explained (Sorond et al, 2011; Jokumsen-Cabral et al, 2019). Biomarkers for the events predating irreversible damage could be key for better clinical management and presymptomatic preventive measures

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