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Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women
Heart failure (HF) is a leading cause of death in both men and women. However, risk factors seem to differ for men and women and significant gaps in sex-specific knowledge exist. Mitochondria are critical for cardiomyocytes and in this study, we investigated the role of baseline mitochondrial DNA co...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685522/ https://www.ncbi.nlm.nih.gov/pubmed/36440036 http://dx.doi.org/10.3389/fcvm.2022.1012403 |
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author | Sundquist, Kristina Sundquist, Jan Wang, Xiao Palmer, Karolina Memon, Ashfaque A. |
author_facet | Sundquist, Kristina Sundquist, Jan Wang, Xiao Palmer, Karolina Memon, Ashfaque A. |
author_sort | Sundquist, Kristina |
collection | PubMed |
description | Heart failure (HF) is a leading cause of death in both men and women. However, risk factors seem to differ for men and women and significant gaps in sex-specific knowledge exist. Mitochondria are critical for cardiomyocytes and in this study, we investigated the role of baseline mitochondrial DNA copy number (mtDNA-CN) in HF incidence in middle-aged women and its possible role in the association between myocardial infarction (MI) and HF. Finally, we also investigated whether baseline mtDNA-CN was associated with overall and HF mortality. Baseline levels of mtDNA-CN were quantified by droplet digital PCR in a population-based follow-up study of middle-aged (50–59 years) Swedish women (n = 2,508). The median follow-up period was 17 years. Levels of mtDNA-CN were associated with age, BMI, alcohol, smoking, education, physical activity and lipid biomarkers. Multivariable Cox regression analysis adjusted for potential confounders showed that each standard deviation decrease of baseline mtDNA-CN was associated with higher incidence of HF (HR = 1.34; 95% CI=1.11–1.63). Similar results were obtained when mtDNA-CN levels were categorized into quartiles with lowest vs. highest quartile showing the highest risk of HF incidence (HR = 2.04 95% CI=1.14; 3.63). We could not detect any role of mtDNA-CN in the association between MI and HF incidence. Lower baseline mtDNA-CN levels were associated with both overall (HR = 1.27; 95% CI=1.10–1.46) and HF mortality (HR = 1.93; 95% CI=1.04–3.60); however, in multivariable analysis adjusted for potential confounders, the higher risks of HF mortality were no longer significant (HR=1.57; 95% CI=0.85–2.90). In conclusion, low baseline mtDNA-CN is an easily quantifiable molecular risk factor for HF incidence and may be a risk factor for overall and HF-related mortality. |
format | Online Article Text |
id | pubmed-9685522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96855222022-11-25 Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women Sundquist, Kristina Sundquist, Jan Wang, Xiao Palmer, Karolina Memon, Ashfaque A. Front Cardiovasc Med Cardiovascular Medicine Heart failure (HF) is a leading cause of death in both men and women. However, risk factors seem to differ for men and women and significant gaps in sex-specific knowledge exist. Mitochondria are critical for cardiomyocytes and in this study, we investigated the role of baseline mitochondrial DNA copy number (mtDNA-CN) in HF incidence in middle-aged women and its possible role in the association between myocardial infarction (MI) and HF. Finally, we also investigated whether baseline mtDNA-CN was associated with overall and HF mortality. Baseline levels of mtDNA-CN were quantified by droplet digital PCR in a population-based follow-up study of middle-aged (50–59 years) Swedish women (n = 2,508). The median follow-up period was 17 years. Levels of mtDNA-CN were associated with age, BMI, alcohol, smoking, education, physical activity and lipid biomarkers. Multivariable Cox regression analysis adjusted for potential confounders showed that each standard deviation decrease of baseline mtDNA-CN was associated with higher incidence of HF (HR = 1.34; 95% CI=1.11–1.63). Similar results were obtained when mtDNA-CN levels were categorized into quartiles with lowest vs. highest quartile showing the highest risk of HF incidence (HR = 2.04 95% CI=1.14; 3.63). We could not detect any role of mtDNA-CN in the association between MI and HF incidence. Lower baseline mtDNA-CN levels were associated with both overall (HR = 1.27; 95% CI=1.10–1.46) and HF mortality (HR = 1.93; 95% CI=1.04–3.60); however, in multivariable analysis adjusted for potential confounders, the higher risks of HF mortality were no longer significant (HR=1.57; 95% CI=0.85–2.90). In conclusion, low baseline mtDNA-CN is an easily quantifiable molecular risk factor for HF incidence and may be a risk factor for overall and HF-related mortality. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9685522/ /pubmed/36440036 http://dx.doi.org/10.3389/fcvm.2022.1012403 Text en Copyright © 2022 Sundquist, Sundquist, Wang, Palmer and Memon. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Sundquist, Kristina Sundquist, Jan Wang, Xiao Palmer, Karolina Memon, Ashfaque A. Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
title | Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
title_full | Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
title_fullStr | Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
title_full_unstemmed | Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
title_short | Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
title_sort | baseline mitochondrial dna copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685522/ https://www.ncbi.nlm.nih.gov/pubmed/36440036 http://dx.doi.org/10.3389/fcvm.2022.1012403 |
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