Association of mitochondrial DNA copy number in peripheral blood with risk and prognosis in acute aortic syndrome.

Abstract

Previous studies have reported that mtDNA-CN of blood was associated with a series of aging-related diseases. However, it remains unknown whether mtDNA-CN can be a potential biomarker of acute aortic syndromes (AAS). The mtDNA-CN in blood of 190 male patients with AAS and 207 healthy controls were detected by standardized qPCR-based assay. The mtDNA sequencing data of blood and myocardial muscle in 134 individuals were used to analyze mtDNA somatic mutations in blood. MtDNA-CN in peripheral blood was negatively correlated with age of individuals. Further analysis based on NGS data demonstrated numbers and heteroplasmy of mtDNA mutations were positively correlated with age. Remarkably, mtDNA-CN of AAS patients was lower than that of healthy controls. Logistic regression also showed that mtDNA-CN was independently associated with risk of AAS. During follow-up, patients with the lowest mtDNA-CN quartile had HR of 2.543 for all-cause-mortality and 1.964 for composite endpoints compared with the other patients. Moreover, multivariate COX regression indicated that lowest mtDNA-CN quartile was independently associated with all-cause mortality in AAS patients. Our study demonstrated a negative correlation between mtDNA-CN and age. Moreover, lower mtDNA-CN in peripheral blood was significantly associated with higher risk and worse prognosis of AAS. It provided crucial evidence supporting the potential of mtDNA-CN as a novel biomarker of AAS.