Increasing studies have explored the correlation of mitochondrial DNA copy number (mtDNA-CN) abnormalities with cardiovascular disease (CVD) and all-cause mortality
however, their findings are contradictory. This systematic review and meta-analysis sought to quantitatively summarize current studies to elucidate the impact of mtDNA-CN on CVD outcomes and all-cause mortality. Relevant studies were searched for in PubMed, Embase and Web of Science databases, up to 23 October 2023. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated with the random-effects model. In total, 22 articles were included in the systematic review, 13 of which were included in the meta-analysis of CVD outcomes and 8 in all-cause mortality. Compared to the highest mtDNA-CN level, the summary RR (95% CI) for the lowest mtDNA-CN level was 2.09 (95% CI 1.59-2.75) for CVD, 1.70 (95% CI 1.29-2.24) for coronary heart disease (CHD), 1.43 (95% CI 1.15-1.79) for heart failure (HF), 1.88 (95% CI 1.08-3.28) for stroke and 1.33 (95% CI 1.21-1.47) for all-cause mortality. Lower mtDNA-CN may increase the risk of CVD, including CHD, HF and stroke, as well as all-cause mortality. MtDNA-CN is a potential predictor of CVD and all-cause mortality.