Huang Jin, Tan Lun, Shen Rufei, Zhang Lina, Zuo Houjuan, Wang Dao W
From the Division of Cardiology, Departments of Internal Medicine and The Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Medicine (Baltimore). 2016 Apr;95(15):e3323. doi: 10.1097/MD.0000000000003323.
Mitochondrial DNA (mtDNA) copy number variation (CNV), which reflects the oxidant-induced cell damage, has been observed in a wide range of human diseases. However, whether it correlates with heart failure, which is closely related to oxidative stress, has never been elucidated before. We aimed to systematically investigate the associations between leukocyte mtDNA CNV and heart failure risk and prognosis. A total of 1700 hospitalized patients with heart failure and 1700 age- and sex-matched community population were consecutively enrolled in this observational study, as well as 1638 (96.4%) patients were followed prospectively for a median of 17 months (12-24 months). The relative mtDNA copy number of leukocyte of peripheral blood or cardiac tissue was measured in triplicate by quantitative real-time PCR method. Patients with heart failure possessed much lower relative mtDNA copy number compared with control subjects (median 0.83, interquartile range [IQR] 0.60-1.16 vs median 1.00, IQR 0.47-2.20; P < 0.001), especially for the patients with ischemic etiology (median, 0.77 for ischemic and 0.91 for non-ischemic, P < 0.001). Patients with lower mtDNA copy number exhibited 1.7 times higher risk of heart failure (odds ratio 1.71, 95% confidence interval [CI] 1.48-1.97, P < 0.001). Long-term follow-up (median of 17 months) showed that decreased mtDNA copy number was significant associated with both increased cardiovascular deaths (hazard ratio [HR] 1.58, 95% CI 1.16-2.16, P = 0.004) and cardiovascular rehospitalization (HR 1.48, 95% CI 1.21-1.82, P < 0.001). After adjusting for the conventional risk factors and medications, lower mtDNA copy numbers were still significantly associated with 50% higher cardiovascular mortality (P = 0.035). In conclusion, mtDNA copy number depletion is an independent risk factor for heart failure and predicts higher cardiovascular mortality in patients with heart failure.
线粒体DNA（mtDNA）拷贝数变异（CNV）反映了氧化剂诱导的细胞损伤，已在多种人类疾病中被观察到。然而，它是否与与氧化应激密切相关的心力衰竭相关，此前从未得到阐明。我们旨在系统地研究白细胞mtDNA CNV与心力衰竭风险及预后之间的关联。本观察性研究连续纳入了1700例住院心力衰竭患者和1700例年龄及性别匹配的社区人群，并且对1638例（96.4%）患者进行了中位时间为17个月（12 - 24个月）的前瞻性随访。采用定量实时PCR方法对三份外周血或心脏组织白细胞的相对mtDNA拷贝数进行测量。与对照组相比，心力衰竭患者的相对mtDNA拷贝数低得多（中位数0.83，四分位数间距[IQR] 0.60 - 1.16，而对照组中位数为1.00，IQR 0.47 - 2.20；P＜0.001），尤其是缺血性病因的患者（缺血性患者中位数为0.77，非缺血性患者为0.91，P＜0.001）。mtDNA拷贝数较低的患者发生心力衰竭的风险高1.7倍（比值比1.71，95%置信区间[CI] 1.48 - 1.97，P＜0.001）。长期随访（中位时间17个月）显示，mtDNA拷贝数降低与心血管死亡增加（风险比[HR] 1.58，95% CI 1.16 - 2.16，P = 0.004）和心血管再住院（HR 1.48，95% CI 1.21 - 1.82，P＜0.001）均显著相关。在调整了传统风险因素和药物治疗后，较低的mtDNA拷贝数仍与心血管死亡率高50%显著相关（P = 0.035）。总之，mtDNA拷贝数减少是心力衰竭的独立危险因素，并可预测心力衰竭患者更高的心血管死亡率。
