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Prognostic value of mitochondrial DNA 4977 deletion and mitochondrial DNA copy number in patients with stable coronary artery disease.
- Source :
-
Atherosclerosis [Atherosclerosis] 2018 Sep; Vol. 276, pp. 91-97. Date of Electronic Publication: 2018 Jul 25. - Publication Year :
- 2018
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Abstract
- Background and Aims: Mitochondrial DNA copy number (mtDNA-CN) depletion has been recently associated with an increased cardiovascular risk. However, the integrity of mtDNA is another key aspect of the energy metabolism and mitochondrial function. We investigated the prognostic role of peripheral blood common mitochondrial deletion (mtDNA <superscript>4977</superscript> ) and mtDNA-CN on long-term major adverse cardiac events (MACEs) and all-cause mortality in a cohort of patients with coronary artery disease (CAD).<br />Methods: Within the Italian GENOCOR (Genetic Mapping for Assessment of Cardiovascular Risk) cohort, we studied 515 patients (450 males, 65 ± 8 years) with known or suspected stable CAD. mtDNA <superscript>4977</superscript> deletion and mtDNA-CN were assessed in peripheral blood using qRT-PCR.<br />Results: During a mean follow-up of 4.5 ± 1.1 years, 78 (15%) patients had MACEs (15 cardiac deaths, 17 nonfatal myocardial infarction and 46 coronary revascularizations) and 28 patients died for non-cardiac causes. Patients with high levels of mtDNA <superscript>4977</superscript> deletion (>75th) had increased risk of MACEs (log rank = 7.2, p=0.007) and all-cause mortality (log rank = 5.7, p=0.01) compared with patients with low mtDNA <superscript>4977</superscript> deletion (≤75th). Multivariate Cox regression analysis showed that log mtDNA <superscript>4977</superscript> was a significant predictor of MACEs (HR = 2.17; 95% CI, 1.31-3.59; p=0.003) and all-cause mortality (HR = 2.03; 95% CI: 1.13-3.65, p=0.02). Log mtDNA-CN was not significantly associated with MACEs or all-cause mortality. However, patients with high mtDNA <superscript>4977</superscript> deletion (>75th) and low mtDNA-CN (<25th) had significantly increased risk for MACEs (HR: 3.73; 95% CI: 1.79-7.79; p=0.0005).<br />Conclusions: Mitochondria DNA damage was associated with an increased risk of MACEs and all-cause mortality in patients with stable CAD, confirming the critical role of mitochondrial dysfunction in atherosclerosis.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Aged
Cause of Death
Coronary Artery Disease blood
Coronary Artery Disease mortality
Coronary Artery Disease therapy
DNA, Mitochondrial blood
Female
Genetic Markers
Genetic Predisposition to Disease
Humans
Italy
Male
Middle Aged
Myocardial Infarction genetics
Myocardial Infarction mortality
Myocardial Infarction therapy
Myocardial Revascularization
Phenotype
Prognosis
Risk Assessment
Risk Factors
Coronary Artery Disease genetics
DNA Copy Number Variations
DNA, Mitochondrial genetics
Gene Deletion
Gene Dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 276
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 30053637
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2018.07.015