Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sundquist, Kristina, Sundquist, Jan, Wang, Xiao, Palmer, Karolina, Memon, Ashfaque A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784835527490404352
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
work_keys_str_mv AT sundquistkristina baselinemitochondrialdnacopynumberandheartfailureincidenceanditsroleinoverallandheartfailuremortalityinmiddleagedwomen
AT sundquistjan baselinemitochondrialdnacopynumberandheartfailureincidenceanditsroleinoverallandheartfailuremortalityinmiddleagedwomen
AT wangxiao baselinemitochondrialdnacopynumberandheartfailureincidenceanditsroleinoverallandheartfailuremortalityinmiddleagedwomen
AT palmerkarolina baselinemitochondrialdnacopynumberandheartfailureincidenceanditsroleinoverallandheartfailuremortalityinmiddleagedwomen
AT memonashfaquea baselinemitochondrialdnacopynumberandheartfailureincidenceanditsroleinoverallandheartfailuremortalityinmiddleagedwomen