Cerebrovascular and Cardiovascular Health in Patients Following Acute Stroke

Hoad, K ORCID: 0000-0003-1266-3269 (2025) Cerebrovascular and Cardiovascular Health in Patients Following Acute Stroke. Doctoral thesis, Liverpool John Moores University.

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Abstract

Stroke, defined as an insufficient or disrupted blood supply to the brain (ischaemic stroke) or rupture of a vessel (haemorrhagic stroke), results in neuronal injury and loss of brain function. The condition is characterised by complex pathophysiological changes, including disrupted cerebrovascular function and systemic cardiovascular responses. Ischaemic stroke increases the risk of mortality, recurrent events, and cardiovascular complications (e.g. atrial fibrillation). Among the stroke types, intracerebral haemorrhage, characterised by rupture of small penetrating arteries within the brain tissue, accounts for approximately 10% of all cases and is associated with early mortality and worsened prognosis.

Individuals who have experienced a stroke typically exhibit reduced mobility and spend a greater proportion of time engaged in sedentary behaviour. Sedentary behaviour is also a risk factor for cardiovascular mortality and morbidity, independent of physical activity levels. Uninterrupted and prolonged sedentary behaviour can compromise cerebral blood flow (CBF) and cerebrovascular mechanisms, such as cerebral autoregulation and cerebrovascular reactivity. Stroke can cause impairments to these cerebrovascular mechanisms and altered haemodynamics following stroke. Despite associations between sedentary behaviour and stroke, little is known about the influence of sedentary behaviour on cerebrovascular function in those with stroke. Consequently, the overarching aim of this thesis was to investigate the impact of stroke on cerebrovascular and cardiovascular health and explore if sedentary behaviour impacts this relationship.

Given the high burden of cardiovascular complications following ischaemic stroke, chapter 3 focused on intracerebral haemorrhage and newly diagnosed cardiovascular complications. Chapter 3 (study one) investigated the incidence and 5-year major adverse cardiovascular events (MACE) of newly diagnosed cardiovascular
complications following intracerebral haemorrhage, using a global federated database. Results showed that 15% of patients with non-traumatic intracerebral haemorrhage had one or more newly diagnosed cardiovascular complications within 4 weeks following stroke onset, also known as stroke-heart syndrome. When compared to those without newly diagnosed cardiovascular complications, patients with intracerebral haemorrhage and newly diagnosed cardiovascular complications were associated with a significantly higher risk of 5-year MACE (Hazard Ratio (HR) 1.35, 95% CI 1.32-1.38). This study highlights that patients with intracerebral haemorrhage and a newly diagnosed cardiovascular complication were at a greater risk of worsened 5-year prognosis.

Chapter 4 (study two) aimed to examine the association between patient characteristics at admission and stroke characteristics on cerebrovascular function and sedentary behaviour following ischaemic stroke. Results showed significant overall effects of sedentary level on combined hypercapnic challenge (F(4,45) = 2.59, p = 0.05, ŋ2 = 0.19) and hypocapnic challenges (F (4,41) = 6.12, p < 0.001). Additionally, absolute CO2 changes in hypercapnic and hypocapnic challenges were negatively associated with prolonged sedentary bouts (60-120 minutes, p ≤ 0.02). Impaired cerebrovascular reactivity was associated with lacunar strokes during the hypercapnic challenge (p = 0.01), and with older age and mild stroke severity during the hypocapnic challenges (p = 0.04). Impaired cerebral autoregulation (transfer function analysis parameters) was associated with high levels of sedentary behaviour when older in age (p = 0.02). The findings suggest that prolonged bouts of sedentary time, not necessarily total sedentary time, may be an important consideration for cerebrovascular function in stroke survivors.

Chapter 5 (study three) examined the association between cerebrovascular function, and 12-month MACE and patient-reported outcomes, moderated by sedentary behaviour following ischaemic stroke. There were no associations between cerebrovascular function and patient-reported outcomes and the risk of MACE in the overall cohort in 12 months, regardless of sedentary levels. In the sensitivity analyses within 6- and 12-months, the sensitivity analysis within 12 months was found to show that impaired cerebrovascular reactivity to CO2 was associated with worsened 12- month patient-reported outcomes (i.e., depression, anxiety, health-related quality of life) and both analyses within 6- and 12 months showed an increased risk of MACE (hypercapnic challenge: OR 1.37 and 1.45, respectively; hypocapnic challenge: OR 2.21 and 1.58, respectively) when sedentary levels were high.

Taken together this thesis provides (i) greater insight into stroke-heart syndrome and intracerebral haemorrhage, and (ii) the first evidence that sedentary behaviour associates with cerebrovascular function and may worsen prognosis.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	Stroke; Sedentary Behaviour; Cerebrovascular Function; Cardiovascular Disease; Patient Report Outcomes
Subjects:	R Medicine > R Medicine (General)
Divisions:	Sport and Exercise Sciences
Date of acceptance:	20 November 2025
Date Deposited:	23 Jan 2026 11:28
Last Modified:	23 Jan 2026 11:28
DOI or ID number:	10.24377/LJMU.t.00027806
Supervisors:	Buckley, B, Jones, H and Miller, G
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27806

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