Chronic hyperglycemia before acute ischemic stroke impairs the bilateral cerebrovascular response to exercise during the subacute recovery period

 So what? What is your solution to that problem? NO SOLUTION, YOU DID USELESS RESEARCH. 

I can see no purpose for including the term bilateral in the title.

Chronic hyperglycemia before acute ischemic stroke impairs the bilateral cerebrovascular response to exercise during the subacute recovery period

Carolyn S. Kaufman

Stephen X. Bai

Sarah M. Eickmeyer

Sandra A. Billinger

First published: 08 December 2020

https://doi.org/10.1002/brb3.1990

Abstract

Background and Purpose

Chronic hyperglycemia contributes to cerebrovascular dysfunction by damaging blood vessels. Poor glucose control has been tied to impairments in cerebral blood flow, which may be particularly detrimental for people recovering from major cerebrovascular events such as acute ischemic stroke. In this secondary analysis, we explore for the first time the connection between chronic hyperglycemia before acute stroke and the cerebrovascular response (CVR) to exercise 3 and 6 month into the subacute recovery period.

Methods

We recorded middle cerebral artery velocity (MCAv) using transcranial Doppler ultrasound bilaterally at rest and during moderate‐intensity exercise in stroke patients at 3 (n = 19) and 6 (n = 12) months post‐stroke. We calculated CVR as the difference between MCAv during steady‐state exercise and resting MCAv. We obtained hemoglobin A1c levels (HbA1c; a measure of blood glucose over the prior 3 months) from the electronic medical record (EMR) and divided participants by HbA1c greater or less than 7%.

Results

Participants with high HbA1c (>7%) at the time of acute stroke had significantly lower CVR to exercise for both the stroke‐affected (p = .009) and non‐affected (p = .007) hemispheres at 3 months post‐stroke. These differences remained significant at 6 months post‐stroke (stroke‐affected, p = .008; non‐affected, p = .016).

Conclusions

Patients with chronic hyperglycemia before acute ischemic stroke demonstrated impaired cerebrovascular function during exercise months into the subacute recovery period. These findings highlight the importance of maintaining tight glucose control to reduce morbidity and improve recovery post‐stroke and could have implications for understanding cerebrovascular pathophysiology.

1 INTRODUCTION

Chronic hyperglycemia causes systemic vascular damage. (Duckworth et al., 2009; Hemmingsen et al., 2011; Patel et al., 2008) Therefore, the American College of Physicians (ACP) and American Diabetes Association (ADA) recommend long‐term glucose control—specifically, a hemoglobin A1c (HbA1c) level below 7%—in order to minimize severity and frequency of vascular complications in diabetes mellitus (DM) (Qaseem et al., 2018; Targets, 2019). Without adequate control, chronic hyperglycemia increases the risk of stroke and negatively affects cerebrovascular function in other neurological disorders such as Alzheimer's disease and vascular cognitive impairment. (Ergul et al., 2012) Elevated blood glucose causes damage to both large and small vessels with increasing evidence that stroke and vascular cognitive impairment are the result of a combination of pathology in both types of cerebral vessels. (Huber, 2008) Reduced middle cerebral artery velocity (MCAv), a surrogate measure of cerebral blood flow (CBF), has been reported in those with DM at rest and in response to stimuli (e.g., hypercapnia) when compared to control groups. (Cui et al., 2017; Jansen et al., 2016; Kadoi et al.,; Novak et al., 2006) Additionally, we previously reported that cognitively normal older adults with higher cardiovascular risk level, including those with DM, have lower MCAv at rest and in response to moderate‐intensity exercise. (Perdomo et al.,)

In people with stroke, DM is often a comorbid condition along with other traditional cardiovascular risk factors. (Kernan et al., 2014) Two recent reports have shown that people with stroke may have altered cerebrovascular function when compared to their peers. (Kempf & A., Lui, Y., 2019; Robertson et al., 2019) However, specific contributing factors to this cerebrovascular dysfunction, such as chronic hyperglycemia (HbA1c > 7%), have yet to be explored. Thus, it is unknown whether chronic hyperglycemia in the months prior to acute ischemic stroke affects resting and exercising MCAv during the subacute stage of stroke recovery.

To address this gap in the literature, the objective of this secondary analysis was to explore whether elevated HbA1C at the time of acute stroke was associated with impaired MCAv measures during rest and exercise at 3 and 6 months post‐stroke. Specifically, we divided participants into those with chronically uncontrolled blood glucose (defined according to ADA and ACP guidelines as HbA1c > 7%) or controlled blood glucose (HbA1c < 7%) at the time of acute stroke. We hypothesized that the group with elevated HbA1c would have: 1) lower resting MCAv, 2) reduced cerebrovascular response to exercise (CVR, defined as exercising MCAv – resting MCAv), and 3) smaller percent change in MCAv (%ΔMCAv, calculated to control for resting baseline values) from rest to exercise at 3 and 6 months post‐stroke. As an exploratory aim, we evaluated the CVR in participants stratified by Type 2 DM diagnosis with the hypothesis that the CVR would be significantly negatively correlated with HbA1c level for individuals with Type 2 DM.