Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium

Published: 5 September 2023| Version 1 | DOI: 10.17632/srzn6fj2hz.1
Bingxin Gong, Yu Sheng Guo, Yi Li, Jing Wang, Guo feng Zhou, Yong-hao Chen, Tong Nie, Ming Yang, Kun Luo, Chuansheng Zheng, Feng Pan, Bo Liang, Lian Yang


Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced cancer. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. Our study included patients diagnosed with stage III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during follow-up chest CT scans at baseline and 3, 6, and 12 months after treatment. The primary endpoint of this study was the occurrence of atherosclerotic cardiovascular disease (ASCVD) events, including myocardial infarction, coronary revascularization, and ischemic stroke. Secondary endpoint was the CAC progression at three time points after treatment.


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Patient characteristics at baseline were collected from medical records. We collected non-ECG-gated CAC data of patients at baseline and at 3, 6, and 12 months (± 30 days) after treatment from chest CT scans. Imaging parameters were as follows: slice thickness, 1.5 to 2.0 mm; tube current, modulated automatically; tube voltage, 120 kV; and image reconstruction, standard soft convolution kernel. Two independent radiologists manually outlined the region of interest in four coronary arteries (the left main trunk, left anterior descending artery, circumflex, and right coronary artery) utilizing semiautomatic software (CaScoring, Syngo, Siemens Healthineers). The software automatically calculated the CAC volume and score in each coronary artery and the total (with an attenuation ≥ 130 HU and an area ≥ 1.0 mm2). The primary endpoint of this study was the occurrence of ASCVD events, which included myocardial infarction, coronary revascularization, and ischemic stroke. Potential events were assessed through the review of imaging, medical records for hospitalizations and outpatients, death certificates, and discharge summaries. A telephonic interview was conducted with each patient or a family member. Secondary endpoints included the progression of CAC volume and score after treatment. All patients were followed up until April 2023 or death.


Wuhan Union Hospital, Huazhong University of Science and Technology Tongji Medical College


Lung Cancer, Cardiovascular Disease, Immune Checkpoint Inhibitor


National Natural Science Foundation of China