Association between mitochondrial DNA copy number and cardiovascular disease: Current evidence based on a systematic review and meta-analysis

Background: Mitochondria are energy-producing structure of the cell and help to maintain redox environment. In cardiovascular disease, the number of mitochondrial DNA (mtDNA) will changes accordingly compare to normal condition. Some investigators ask whether it has a clear association between mtDNA and cardiovascular disease with its adverse events. Thus, we conduct the meta-analysis to assess the role of circulating mtDNA in evaluating cardiovascular disease. Methods: The meta-analysis was conducted in accordance with a predetermined protocol following the recommendations of Cochrane Handbook of Systematic Reviews. We searched the Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center to identify relevant studies up to the end of October 2017. Data were analyzed using STATA. Besides, publication bias and meta-regression analysis were also conducted. Results: We collected results from 5 articles for further analyses with 8,252 cases and 20,904 control. The normalized mtDNA copy number level is lower in cardiovascular disease (CVD) than the control groups with a pooled standard mean difference (SMD) of -0.36(95%CI,-0.65 to -0.08); The pooled odds ratio (OR) for CVD proportion associated with a 1-SD (standard deviation) decrease in mtDNA copy number level is 1.23 (95% CI,1.06–1.42); The OR for CVD patients with mtDNA copy number lower than median level is 1.88(95% CI,1.65–2.13); The OR for CVD patients with mtDNA copy number located in the lowest quartile part is 2.15(95% CI, 1.46–3.18); the OR between mtDNA copy number and the risk of sudden cardiac death (SCD) is 1.83(95% CI, 1.22–2.74). Conclusion: Although inter-study variability, the overall performance test of mtDNA for evaluating CVD and SCD revealed that the mtDNA copy number presented the potential to be a biomarker for CVD and SCD prediction. Given that, the fewer copies of mtDNA, the higher the risk of CVD.