Biological heart and brain ageing in subjects with cardiovascular diseases

IntroductionThe heart-brain axis hypothesis suggests a bidirectional connection between the brain and the heart with relevant implications in health and disease. Cardiovascular diseases have been empirically linked to an increased risk of neurological diseases. However, it remains unclear to what ex...

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Main Authors: Elizabeth Mcavoy, Matthias Wilms, Nils D. Forkert
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1569423/full
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author Elizabeth Mcavoy
Elizabeth Mcavoy
Elizabeth Mcavoy
Matthias Wilms
Matthias Wilms
Matthias Wilms
Matthias Wilms
Matthias Wilms
Nils D. Forkert
Nils D. Forkert
Nils D. Forkert
Nils D. Forkert
author_facet Elizabeth Mcavoy
Elizabeth Mcavoy
Elizabeth Mcavoy
Matthias Wilms
Matthias Wilms
Matthias Wilms
Matthias Wilms
Matthias Wilms
Nils D. Forkert
Nils D. Forkert
Nils D. Forkert
Nils D. Forkert
author_sort Elizabeth Mcavoy
collection DOAJ
description IntroductionThe heart-brain axis hypothesis suggests a bidirectional connection between the brain and the heart with relevant implications in health and disease. Cardiovascular diseases have been empirically linked to an increased risk of neurological diseases. However, it remains unclear to what extent different cardiovascular diseases affect brain health quantitatively across subjects and if that is associated with the extent the heart is affected by a disease. Therefore, this study aims to explore how cardiovascular diseases affect biological ageing of the brain and heart by quantifying the brain age gap (BAG) and the heart age gap (HAG) and relating the two to each other.MethodsThis study used data from UK Biobank participants with available T1-weighted brain magnetic resonance imaging (MRI) scans, cardiac MRI-derived features, as well as pulse wave analysis cardiac measurements. This dataset included 7,500 healthy females and 6,684 healthy males. The data from healthy subjects was used to train biological brain age prediction machine learning models. For BAG computation, a convolutional neural network was trained based on the MRI data, while a CatBoost model was trained for HAG analyses based on the tabulated cardiac features. Individuals with cardiovascular diseases (F = 2,304, M = 2,925) in the UK Biobank were categorized using Phecodes and split based on sex and used to calculate the HAG and BAG for further analyses.ResultsIn 36 sex-specific cardiovascular disease groups, 24 showed significant differences from healthy subjects in the BAG and HAG distributions, whereas no strong correlations between the BAG and HAG distributions within disease groups were found. However, some diseases, such as hypotension and cardiac conduction disorders, showed sex-specific differences.DiscussionThis study demonstrates that the combined use of HAG and BAG biomarkers provides a more comprehensive understanding of the interplay between cardiovascular and neurological ageing. The significant differences observed in disease groups, while lacking a strong correlation between the BAG and HAG, questions the generalizability of the heart-brain axis theory with respect to age gap biomarkers, suggesting potentially heterogeneous aging processes of the two systems that warrant further investigation in future work.
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spelling doaj-art-3afb3d4f7f7e45fb9f4e46c38c365d1a2025-08-20T03:33:08ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-07-011210.3389/fcvm.2025.15694231569423Biological heart and brain ageing in subjects with cardiovascular diseasesElizabeth Mcavoy0Elizabeth Mcavoy1Elizabeth Mcavoy2Matthias Wilms3Matthias Wilms4Matthias Wilms5Matthias Wilms6Matthias Wilms7Nils D. Forkert8Nils D. Forkert9Nils D. Forkert10Nils D. Forkert11Department of Radiology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaDepartment of Biomedical Engineering, University of Calgary, Calgary, AB, CanadaDepartment of Radiology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaDepartment of Pediatrics, University of Calgary, Calgary, AB, CanadaDepartment of Community Health Sciences, University of Calgary, Calgary, AB, CanadaDepartment of Radiology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaDepartment of Clinical Neuroscience, University of Calgary, Calgary, AB, CanadaIntroductionThe heart-brain axis hypothesis suggests a bidirectional connection between the brain and the heart with relevant implications in health and disease. Cardiovascular diseases have been empirically linked to an increased risk of neurological diseases. However, it remains unclear to what extent different cardiovascular diseases affect brain health quantitatively across subjects and if that is associated with the extent the heart is affected by a disease. Therefore, this study aims to explore how cardiovascular diseases affect biological ageing of the brain and heart by quantifying the brain age gap (BAG) and the heart age gap (HAG) and relating the two to each other.MethodsThis study used data from UK Biobank participants with available T1-weighted brain magnetic resonance imaging (MRI) scans, cardiac MRI-derived features, as well as pulse wave analysis cardiac measurements. This dataset included 7,500 healthy females and 6,684 healthy males. The data from healthy subjects was used to train biological brain age prediction machine learning models. For BAG computation, a convolutional neural network was trained based on the MRI data, while a CatBoost model was trained for HAG analyses based on the tabulated cardiac features. Individuals with cardiovascular diseases (F = 2,304, M = 2,925) in the UK Biobank were categorized using Phecodes and split based on sex and used to calculate the HAG and BAG for further analyses.ResultsIn 36 sex-specific cardiovascular disease groups, 24 showed significant differences from healthy subjects in the BAG and HAG distributions, whereas no strong correlations between the BAG and HAG distributions within disease groups were found. However, some diseases, such as hypotension and cardiac conduction disorders, showed sex-specific differences.DiscussionThis study demonstrates that the combined use of HAG and BAG biomarkers provides a more comprehensive understanding of the interplay between cardiovascular and neurological ageing. The significant differences observed in disease groups, while lacking a strong correlation between the BAG and HAG, questions the generalizability of the heart-brain axis theory with respect to age gap biomarkers, suggesting potentially heterogeneous aging processes of the two systems that warrant further investigation in future work.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1569423/fullbrain age gapheart age gapcardiovascular diseaseageingheart-brain axis
spellingShingle Elizabeth Mcavoy
Elizabeth Mcavoy
Elizabeth Mcavoy
Matthias Wilms
Matthias Wilms
Matthias Wilms
Matthias Wilms
Matthias Wilms
Nils D. Forkert
Nils D. Forkert
Nils D. Forkert
Nils D. Forkert
Biological heart and brain ageing in subjects with cardiovascular diseases
Frontiers in Cardiovascular Medicine
brain age gap
heart age gap
cardiovascular disease
ageing
heart-brain axis
title Biological heart and brain ageing in subjects with cardiovascular diseases
title_full Biological heart and brain ageing in subjects with cardiovascular diseases
title_fullStr Biological heart and brain ageing in subjects with cardiovascular diseases
title_full_unstemmed Biological heart and brain ageing in subjects with cardiovascular diseases
title_short Biological heart and brain ageing in subjects with cardiovascular diseases
title_sort biological heart and brain ageing in subjects with cardiovascular diseases
topic brain age gap
heart age gap
cardiovascular disease
ageing
heart-brain axis
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1569423/full
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