APOE ε4 carriage associates with improved myocardial performance from adolescence to older age
Abstract Background Although APOE ε4 allele carriage confers a risk for coronary artery disease, its persistence in humans might be explained by certain survival advantages (antagonistic pleiotropy). Methods Combining data from ~ 37,000 persons from three older age British cohorts (1946 National Sur...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-024-03808-z |
| _version_ | 1797247449272680448 |
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| author | Constantin-Cristian Topriceanu Mit Shah Matthew Webber Fiona Chan Hunain Shiwani Marcus Richards Jonathan Schott Nishi Chaturvedi James C. Moon Alun D. Hughes Aroon D. Hingorani Declan P. O’Regan Gabriella Captur |
| author_facet | Constantin-Cristian Topriceanu Mit Shah Matthew Webber Fiona Chan Hunain Shiwani Marcus Richards Jonathan Schott Nishi Chaturvedi James C. Moon Alun D. Hughes Aroon D. Hingorani Declan P. O’Regan Gabriella Captur |
| author_sort | Constantin-Cristian Topriceanu |
| collection | DOAJ |
| description | Abstract Background Although APOE ε4 allele carriage confers a risk for coronary artery disease, its persistence in humans might be explained by certain survival advantages (antagonistic pleiotropy). Methods Combining data from ~ 37,000 persons from three older age British cohorts (1946 National Survey of Health and Development [NSHD], Southall and Brent Revised [SABRE], and UK Biobank) and one younger age cohort (Avon Longitudinal Study of Parents and Children [ALSPAC]), we explored whether APOE ε4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional metrics by echocardiography and cardiovascular magnetic resonance (CMR). Results Compared to the non-APOE ε4 group, APOE ε4 carriers had similar cardiac phenotypes in terms of LV ejection fraction, E/e’, posterior wall and interventricular septal thickness, and LV mass. However, they had improved myocardial performance resulting in greater LV stroke volume generation per 1 mL of myocardium (higher myocardial contraction fraction). In NSHD (n = 1467) and SABRE (n = 1187), ε4 carriers had a 4% higher MCF (95% CI 1–7%, p = 0.016) using echocardiography. Using CMR data, in UK Biobank (n = 32,972), ε4 carriers had a 1% higher MCF 95% (CI 0–1%, p = 0.020) with a dose-response relationship based on the number of ε4 alleles. In addition, UK Biobank ε4 carriers also had more favorable radial and longitudinal strain rates compared to non APOE ε4 carriers. In ALSPAC (n = 1397), APOE ε4 carriers aged < 24 years had a 2% higher MCF (95% CI 0–5%, p = 0.059). Conclusions By triangulating results in four independent cohorts, across imaging modalities (echocardiography and CMR), and in ~ 37,000 individuals, our results point towards an association between ε4 carriage and improved cardiac performance in terms of LV MCF. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to the pleiotropic effects APOE ε4 carriage that might collectively explain its persistence in human populations. |
| first_indexed | 2024-04-24T19:58:52Z |
| format | Article |
| id | doaj.art-11cdd86813114bbcb62a5c1ef1c08698 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-04-24T19:58:52Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-11cdd86813114bbcb62a5c1ef1c086982024-03-24T12:09:57ZengBMCBMC Cardiovascular Disorders1471-22612024-03-0124111710.1186/s12872-024-03808-zAPOE ε4 carriage associates with improved myocardial performance from adolescence to older ageConstantin-Cristian Topriceanu0Mit Shah1Matthew Webber2Fiona Chan3Hunain Shiwani4Marcus Richards5Jonathan Schott6Nishi Chaturvedi7James C. Moon8Alun D. Hughes9Aroon D. Hingorani10Declan P. O’Regan11Gabriella Captur12UCL MRC Unit for Lifelong Health and Ageing, University College LondonImperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonUCL Institute of Cardiovascular Science, University College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonUCL Institute of Cardiovascular Science, University College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonUCL Institute of Cardiovascular Science, University College LondonImperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College LondonUCL MRC Unit for Lifelong Health and Ageing, University College LondonAbstract Background Although APOE ε4 allele carriage confers a risk for coronary artery disease, its persistence in humans might be explained by certain survival advantages (antagonistic pleiotropy). Methods Combining data from ~ 37,000 persons from three older age British cohorts (1946 National Survey of Health and Development [NSHD], Southall and Brent Revised [SABRE], and UK Biobank) and one younger age cohort (Avon Longitudinal Study of Parents and Children [ALSPAC]), we explored whether APOE ε4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional metrics by echocardiography and cardiovascular magnetic resonance (CMR). Results Compared to the non-APOE ε4 group, APOE ε4 carriers had similar cardiac phenotypes in terms of LV ejection fraction, E/e’, posterior wall and interventricular septal thickness, and LV mass. However, they had improved myocardial performance resulting in greater LV stroke volume generation per 1 mL of myocardium (higher myocardial contraction fraction). In NSHD (n = 1467) and SABRE (n = 1187), ε4 carriers had a 4% higher MCF (95% CI 1–7%, p = 0.016) using echocardiography. Using CMR data, in UK Biobank (n = 32,972), ε4 carriers had a 1% higher MCF 95% (CI 0–1%, p = 0.020) with a dose-response relationship based on the number of ε4 alleles. In addition, UK Biobank ε4 carriers also had more favorable radial and longitudinal strain rates compared to non APOE ε4 carriers. In ALSPAC (n = 1397), APOE ε4 carriers aged < 24 years had a 2% higher MCF (95% CI 0–5%, p = 0.059). Conclusions By triangulating results in four independent cohorts, across imaging modalities (echocardiography and CMR), and in ~ 37,000 individuals, our results point towards an association between ε4 carriage and improved cardiac performance in terms of LV MCF. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to the pleiotropic effects APOE ε4 carriage that might collectively explain its persistence in human populations.https://doi.org/10.1186/s12872-024-03808-zApolipoprotein ε4Cardiovascular diseaseMyocardial contraction fraction |
| spellingShingle | Constantin-Cristian Topriceanu Mit Shah Matthew Webber Fiona Chan Hunain Shiwani Marcus Richards Jonathan Schott Nishi Chaturvedi James C. Moon Alun D. Hughes Aroon D. Hingorani Declan P. O’Regan Gabriella Captur APOE ε4 carriage associates with improved myocardial performance from adolescence to older age BMC Cardiovascular Disorders Apolipoprotein ε4 Cardiovascular disease Myocardial contraction fraction |
| title | APOE ε4 carriage associates with improved myocardial performance from adolescence to older age |
| title_full | APOE ε4 carriage associates with improved myocardial performance from adolescence to older age |
| title_fullStr | APOE ε4 carriage associates with improved myocardial performance from adolescence to older age |
| title_full_unstemmed | APOE ε4 carriage associates with improved myocardial performance from adolescence to older age |
| title_short | APOE ε4 carriage associates with improved myocardial performance from adolescence to older age |
| title_sort | apoe ε4 carriage associates with improved myocardial performance from adolescence to older age |
| topic | Apolipoprotein ε4 Cardiovascular disease Myocardial contraction fraction |
| url | https://doi.org/10.1186/s12872-024-03808-z |
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