Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction
Yichao Zhao, Xiyuan Lu, Fang Wan, Lingchen Gao, Nan Lin, Jie He, Lai Wei, Jianxun Dong, Zihan Qin, Fangyuan Zhong, Zhiqin Qiao, Wei Wang, Heng Ge, Song Ding, Yining Yang, Jiancheng Xiu, Peiren Shan, Fuhua Yan, Shihua Zhao, Yong Ji, Jun Pu, Yichao Zhao, Xiyuan Lu, Fang Wan, Lingchen Gao, Nan Lin, Jie He, Lai Wei, Jianxun Dong, Zihan Qin, Fangyuan Zhong, Zhiqin Qiao, Wei Wang, Heng Ge, Song Ding, Yining Yang, Jiancheng Xiu, Peiren Shan, Fuhua Yan, Shihua Zhao, Yong Ji, Jun Pu
Abstract
Background: Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.
Objectives: This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI.
Methods: Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models.
Results: Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (β = 5.94%; 95% CI: 2.94-8.94; P < 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury.
Conclusions: The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453).
Keywords: acute myocardial infarction; cardiac magnetic resonance; circadian disruption; inflammation; reperfusion therapy.
Conflict of interest statement
Funding Support and Author Disclosures This work was supported by the National Science Fund for Distinguished Young Scholars (81625002), the National Natural Science Foundation of China (81930007, 81800307, 81770238, 82070477, and 81900373), Shanghai Outstanding Academic Leaders Program (18XD1402400), Shanghai Sailing Program (18YF1413000), the Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZDCX20180200), Shanghai Pujiang Talent Program (2020PJD030), and the Science and Technology Commission of Shanghai Municipality (201409005200 and 19ZR1430400). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed