Pulse lineResearch With Heart Logo

Association of Mitochondrial DNA Copy Number With Cardiovascular Disease.

TitleAssociation of Mitochondrial DNA Copy Number With Cardiovascular Disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsAshar FN, Zhang Y, Longchamps RJ, Lane J, Moes A, Grove ML, Mychaleckyj JC, Taylor KD, Coresh JJ, Rotter JI, Boerwinkle E, Pankratz N, Guallar E
Secondary AuthorsArking DE
JournalJAMA Cardiol
Date Published2017 11 01
KeywordsAged, Atherosclerosis, Blood Buffy Coat, Cardiovascular Diseases, Cohort Studies, Coronary Disease, DNA, Mitochondrial, Female, Humans, Incidence, Leukocytes, Male, Middle Aged, Myocardial Infarction, Proportional Hazards Models, Prospective Studies, Risk Assessment, United States

Importance: Mitochondrial dysfunction is a core component of the aging process and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell and number of mitochondrial genomes per mitochondrion, is an indirect biomarker of mitochondrial function.

Objective: To determine whether mtDNA-CN, measured in an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for cardiovascular disease (CVD) and help guide initiation of statin therapy for primary prevention of CVD.

Design, Setting, and Participants: Prospective, population-based cohort analysis including 21 870 participants (20 163 free from CVD at baseline) from 3 studies: Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities Study (ARIC), and Multiethnic Study of Atherosclerosis (MESA). The mean follow-up was 13.5 years. The study included 11 153 participants from ARIC, 4830 from CHS, and 5887 from MESA. Analysis of the data was conducted from March 10, 2014, to January 29, 2017.

Exposures: Mitochondrial DNA-CN measured from buffy coat/circulating leukocytes.

Main Outcomes and Measures: Incident CVD, which combines coronary heart disease, defined as the first incident myocardial infarction or death owing to coronary heart disease, and stroke, defined as the first nonfatal stroke or death owing to stroke.

Results: Of the 21 870 participants, the mean age was 62.4 years (ARIC, 57.9 years; MESA, 62.4 years; and CHS, 72.5 years), and 54.7% of participants were women. The hazard ratios for incident coronary heart disease, stroke, and CVD associated with a 1-SD decrease in mtDNA-CN were 1.29 (95% CI, 1.24-1.33), 1.11 (95% CI, 1.06-1.16), and 1.23 (95% CI, 1.19-1.26). The associations persisted after adjustment for traditional CVD risk factors. Addition of mtDNA-CN to the 2013 American College of Cardiology/American Heart Association Pooled Cohorts Equations for estimating 10-year hard atherosclerosis CVD risk was associated with improved risk classification (continuous net reclassification index, 0.194; 95% CI, 0.130-0.258; P 

Conclusions and Relevance: Mitochondrial DNA-CN was independently associated with incident CVD in 3 large prospective studies and may have potential clinical utility in improving CVD risk classification.

Alternate JournalJAMA Cardiol
PubMed ID29049454
PubMed Central IDPMC5710361
Grant ListT32 GM007814 / GM / NIGMS NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL131573 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States