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Systemic alterations in vascular morphology and function in men with abdominal aortic aneurysm: With special reference to upper limb arteries and arterial regulation during sympathetic activation
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US.ORCID iD: 0000-0002-8231-0752
2026 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Abdominal aortic aneurysm (AAA) is a pathological dilation of the abdominal aorta affecting ~1% of 65-year-old men in Sweden. AAA is usually asymptomatic until rupture, a catastrophic event with ~80% mortality. No medication currently halts or reverses AAA due to incomplete understanding of its underlying mechanisms. Evidence suggests that AAA may represent a focal manifestation of a systemic vascular disease, supported by observations of enlarged peripheral arteries and altered peripheral arterial regulation. However, whether elastic and muscular arteries are similarly affected remains unclear, and studies of peripheral arterial regulation, venous function, and their impact on overall haemodynamics in AAA are limited. Therefore, this thesis aimed to investigate arterial diameter and function in elastic and muscular arteries of the arm and neck, cardiovascular responses to hypovolemia-induced sympathetic activation, and venous function in individuals with AAA and controls.

Participants were recruited from a regional AAA screening program. The radial- (RA), distal brachial- (BAdist), proximal brachial- (BAprox), axillary- (AXA), and common carotid artery (CCA) were scanned using ultrasound. Arterial diameter, wall thickness, and arterial stiffness were assessed using manual and software-assisted methods. Venous occlusion plethysmography was used to assess forearm and calf venous compliance and capacitance, as well as forearm vascular resistance while sympathetic activation was induced using lower body negative pressure (LBNP).

We found that individuals with AAA exhibited larger and stiffer elastic arteries and similar arterial wall thickness across all arteries compared with controls. In response to increasing LBNP, individuals with AAA displayed blood pressure instability, impaired forearm vascular resistance, and reduced mobilisation of forearm venous blood. Forearm venous compliance was also lower in individuals with AAA compared with controls.

In summary, abdominal aortic aneurysm is associated with marked pathological alterations in elastic arteries, the venous system, and arterial regulation, strengthening the view of AAA being a focal manifestation of a systemic vascular disease.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2026. , p. 96
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 2027
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:liu:diva-221878DOI: 10.3384/9789181184396ISBN: 9789181184389 (print)ISBN: 9789181184396 (electronic)OAI: oai:DiVA.org:liu-221878DiVA, id: diva2:2045866
Public defence
2026-04-17, Berzeliussalen, building 463, Campus US, Linköping, 09:00
Opponent
Supervisors
Note

Funding: Heart and Lung Foundation, Sweden [20160519], Futurum—the Academy for Healthcare, County Council, Jönköping, Sweden [259701], Medical  Research Council of Southeast Sweden (FORSS) [34931], and ALF Grants, Region Östergötland, Linköping, Sweden [LIO-391351, LIO-441081, LIO-541501, RÖ-599961, RÖ- 932252, and RÖ-936189], Region Östergötland, ST-kansliet.

Available from: 2026-03-13 Created: 2026-03-13 Last updated: 2026-03-13Bibliographically approved
List of papers
1. Radial artery lumen diameter and intima thickness in patients with abdominal aortic aneurysm
Open this publication in new window or tab >>Radial artery lumen diameter and intima thickness in patients with abdominal aortic aneurysm
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2022 (English)In: JVS-Vascular Science, ISSN 2666-3503, Vol. 3, p. 274-284Article in journal (Refereed) Published
Abstract [en]

Objective: Abdominal aortic aneurysm (AAA) is associated with dilatation of central elastic arteries, while it is uncertain whether peripheral muscular arteries are affected. The aim of this study was to investigate radial artery diastolic lumen diameter (LD), wall thickness, and circumferential wall stress (CWS) in patients with AAA. Methods: We included 130 men with AAA (mean age, 70.4 ± 3.5 years) and 61 men without AAA (mean age, 70.5 ± 3.2 years) in the study. High-frequency ultrasound examination (50 MHz) was used to measure radial artery diameter, wall thickness, and CWS was calculated. Results: Men with AAA exhibited smaller radial artery LD (2.34 ± 0.42 mm vs 2.50 ± 0.38 mm; P <.01), thicker intima (0.094 ± 0.024 mm vs 0.081 ± 0.018 mm; P <.001), similar intima-media (0.28 ± 0.05 vs 0.26 ± 0.05 mm; P = NS), and lower CWS (42.9 ± 10.2 kPa vs 48.6 ± 11.4 kPa; P <.001), compared with controls. Subgroup analyses including all patients showed smaller LD and thicker intima in patients on statin therapy versus no statin therapy and current/ex-smoking versus never smoking. Individuals with hypertension versus no hypertension also presented with thicker intima, but with no difference in LD. Conclusions: AAAs demonstrated a smaller LD and thicker intima in the radial artery, in contrast with the theory of a general dilating diathesis of the arteries. Apart from AAA, other factors such as atherosclerosis, smoking habits, and hypertension might also be determinants of radial artery caliber and thickness. Clinical Relevance: The clinical relevance of this study is the added insight into the pathophysiology of abdominal aortic aneurysm (AAA). Today, the management of AAA is focused on reduction of general cardiovascular risk factors and treatment is based on surgical approaches when the AAA is already manifest. By shedding light on unknown pathophysiological aspects of AAA, it will eventually be possible to develop targeted pharmacological treatments to prevent the formation of AAA, to halt disease progression, and to find early cardiovascular markers of AAA. © 2022 Society for Vascular Surgery

Place, publisher, year, edition, pages
Elsevier Inc., 2022
Keywords
Abdominal; Aortic aneurysm; Atherosclerosis; Hypertension; Tunica intima; Ultra-high-frequency ultrasound
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-193313 (URN)10.1016/j.jvssci.2022.06.001 (DOI)001394699600020 ()36052216 (PubMedID)2-s2.0-85136263614 (Scopus ID)
Note

Funding Agencies|ALF Grants, Region Östergötland, Linköping, Sweden: RÖ-599961, RÖ-932252, RÖ-936189

Available from: 2023-05-01 Created: 2023-05-01 Last updated: 2026-03-13
2. Increased diameter and stiffness of elastic but not muscular arteries in men with abdominal aortic aneurysm
Open this publication in new window or tab >>Increased diameter and stiffness of elastic but not muscular arteries in men with abdominal aortic aneurysm
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2024 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 136, no 6, p. 1410-1417Article in journal (Refereed) Published
Abstract [en]

It has been proposed that formation of abdominal aortic aneurysm (AAA) is part of a systemic arterial dilatative disease. However, arteries in the upper extremities are scarcely studied and it remains unclear whether both muscular and elastic arteries are affected by the proposed systemic arterial dilatation. The aim of this study was to investigate the diameter and stiffness of muscular and elastic arteries in arterial branches originating from the aortic arch. Twenty-six men with AAA (69 +/- 4 yr) and 57 men without AAA (70 +/- 5 yr) were included in the study. Ultrasound was used to examine the distal and proximal brachial artery, axillary artery, and common carotid artery (CCA), and measurement of diameter and diameter change was performed with wall-tracking software. Blood pressure measurements were used to calculate local arterial wall stiffness indices. The AAA cohort presented larger arterial diameters in the CCA and axillary artery after adjustment for body surface area (P = 0.002, respectively), whereas the brachial artery diameters were unchanged. Indices of increased stiffness in CCA (e.g., lower distensibility, P = 0.003) were seen in subjects with AAA after adjustments for body mass index and mean arterial blood pressure. This study supports the theory of a systemic arterial dilating diathesis in peripheral elastic, but not in muscular, arteries. Peripheral elastic arteries also exhibited increased stiffness, in analogy with findings in the aorta in AAA.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC, 2024
Keywords
arterial stiffness; axillary artery; brachial artery; general dilating diathesis; ultrasound
National Category
Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:liu:diva-206632 (URN)10.1152/japplphysiol.00875.2023 (DOI)001248298900003 ()38660725 (PubMedID)
Note

Funding Agencies|Futurum-the Academy for Healthcare, County Council, Jonkoping, Sweden [259701]; Medical Research Council of Southeast Sweden (FORSS) [34931]; ALF Grants, Region Ostergotland, Linkoping, Sweden [ROE-599961, ROE-932252, ROE-936189]

Available from: 2024-08-21 Created: 2024-08-21 Last updated: 2026-03-13
3. Assessment of Upper Extremity Venous Compliance in Patients With Abdominal Aortic Aneurysms
Open this publication in new window or tab >>Assessment of Upper Extremity Venous Compliance in Patients With Abdominal Aortic Aneurysms
2020 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 60, no 5, p. 739-746Article in journal (Refereed) Published
Abstract [en]

Objective: Abdominal aortic aneurysm (AAA) is associated with morphological and functional changes in both aneurysmal and non-aneurysmal arteries. However, it remains uncertain whether similar changes also exist in the venous vasculature. The aim of this study was to evaluate global venous function in patients with AAA and controls. Methods: This experimental study comprised 31 men with AAA (mean +/- standard deviation age 70.0 +/- 2.8 years) and 29 male controls (aged 70.6 +/- 3.4 years). Venous occlusion plethysmography (VOP) was used to evaluate arm venous compliance at venous pressures between 10 and 60 mmHg in steps of 5 mmHg. Compensatory mobilisation of venous capacitance blood (capacitance response) was measured with a volumetric technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). Results: The VOP induced pressure-volume curve was significantly less steep in patients with AAA (interaction, p < .001), indicating lower venous compliance. Accordingly, the corresponding pressure-compliance curves displayed reduced venous compliance at lower venous pressures in patients with AAA vs. controls (interaction, p < .001; AAA vs. control, p = .018). After adjusting for arterial hypertension, diabetes mellitus, hyperlipidaemia, chronic obstructive pulmonary disease, and smoking, VOP detected differences in venous compliance remained significant at low venous pressures, that is, at 10 mmHg (p = .008), 15 mmHg (p = .013), and 20 mmHg (p = .026). Mean venous compliance was negatively correlated with aortic diameter (r = -.332, p = .010). Mobilisation of venous capacitance response during LBNP was reduced by approximately 25% in patients with AAA (p = .030), and the redistribution of venous blood during LBNP was negatively correlated with aortic diameter (r = -.417, p = .007). Conclusion: Men with AAA demonstrated reduced venous compliance and, as a result, a lesser capacity to mobilise peripheral venous blood to the central circulation during hypovolaemic stress. These findings imply that the AAA disease may be accompanied by functional changes in the venous vascular wall.

Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2020
Keywords
Abdominal aortic aneurysm; Lower body negative pressure; Venous capacitance; Venous compliance; Venous occlusion plethysmography
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-171662 (URN)10.1016/j.ejvs.2020.07.009 (DOI)000587341100021 ()32778487 (PubMedID)
Note

Funding Agencies|Heart and Lung Foundation, SwedenSwedish Heart-Lung Foundation [20160519]; ALF Grants, Region Ostergotland, Linkoping, Sweden [LIO-391351, LIO-441081, LIO-541501]

Available from: 2020-11-30 Created: 2020-11-30 Last updated: 2026-03-13

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Shlimon, Kristian

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