Key result
Low baseline mitochondrial DNA copy number (<111 copies/μL) was associated with an increased risk of incident cardiovascular disease (HR 1.32; 95% CI 1.08-1.63).
Why the study?
Although mitochondrial DNA copy number is linked to both type 2 diabetes and cardiovascular disease, its role in the association between diabetes and cardiovascular disease is unknown.
Does low baseline mitochondrial DNA copy number increase the risk of incident cardiovascular disease in middle-aged women?
Cohort (n=3,062)
Does low baseline mitochondrial DNA copy number increase the risk of incident cardiovascular disease in middle-aged women?
Low baseline mitochondrial DNA copy number is associated with an increased risk of incident cardiovascular disease and may partially mediate the relationship between type 2 diabetes and CVD in middle-aged women.
May flag higher CVD risk in middle-aged women; hypothesis-generating and requires validation before any clinical use.
BACKGROUND AND AIMS: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate biomarker of mitochondrial dysfunction and is associated with type 2 diabetes (T2D) and cardiovascular disease (CVD). However, despite being associated with both CVD and T2D, it is not known what role mtDNA-CN has in the association between T2D and CVD. Our aims were to investigate whether, (1) baseline mtDNA-CN is associated with CVD incidence and (2) mtDNA-CN has a role as a mediator between T2D and CVD. METHOD: We quantified absolute mtDNA-CN by droplet digital PCR method in a population-based follow-up study of middle aged (52-65 years) women (n = 3062). The median follow-up period was 17 years. RESULTS: Our results show that low baseline levels of mtDNA-CN (<111 copies/μL) were associated with an increased risk of CVD (HR = 1.32, 95% CI = 1.08; 1.63) as well as with specific CVDs: coronary heart disease (HR = 1.28, 95% CI = 0.99; 1.66), stroke (HR = 1.26, 95% CI = 0.87; 1.84) and abdominal aortic aneurysm (HR = 2.61, 95% CI = 1.03; 6.62). The associations decreased but persisted even after adjustment for potential confounders. Furthermore, our results show that the total effect of T2D on future risk of CVD was reduced after controlling for mtDNA-CN and the proportion mediated by mtDNA-CN was estimated to be 4.9%. CONCLUSIONS: Lower baseline mtDNA-CN is associated with incident CVD and may have a mediating effect on the association between T2D and CVD; however, this novel observation needs to be confirmed in future studies.
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Sundquist et al. (2021) conducted a cohort in Cardiovascular disease (n=3,062). Low baseline mitochondrial DNA copy number (<111 copies/μL) vs. Higher baseline mitochondrial DNA copy number was evaluated on Incident cardiovascular disease (HR 1.32, 95% CI 1.08-1.63). Low baseline mitochondrial DNA copy number (<111 copies/μL) was associated with an increased risk of incident cardiovascular disease (HR 1.32; 95% CI 1.08-1.63).
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