Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women

• Published in: Frontiers in cardiovascular medicine Vol. 9; p. 1012403
• Main Authors: Sundquist, Kristina, Sundquist, Jan, Wang, Xiao, Palmer, Karolina, Memon, Ashfaque A.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 10-11-2022
• Subjects: Cardiac and Cardiovascular Systems; Cardiovascular Medicine; Clinical Medicine; Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi; Health Sciences; heart failure; Hälsovetenskap; Kardiologi; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; mitochondrial copy number; mitochondrial dysfunction; mortality; Public Health, Global Health, Social Medicine and Epidemiology; risk assessment
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2022.1012403

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.