Resting Heart Rate Mediates the Association Between Circulating Neutrophil Count and Arterial Stiffness Progression: The Kailuan Study

Zhaogui Wu,1,&ast; Dan Wu,2,3,&ast; Shuohua Chen,4 Sichi Xu,5,6 Shunming Zhang,7 Shouling Wu4 1Department of Cardiology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei, 441000, People’s Republic of China; 2Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Centre for Precision Health, Edith Cowan University School of Medical and Health Sciences, Joondalup, WA, Australia; 4Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei, 063001, People’s Republic of China; 5Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China; 6Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China; 7School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shouling Wu, Department of Cardiology, Kailuan General Hospital, No. 57, Xinhuadong Street, Lubei District, Tangshan, Hebei, 063001, People’s Republic of China, Tel +86 13363283666, Email [email protected] Shunming Zhang, School of Public Health, Xi’an Jiaotong University Health Science Center, No. 76, Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86 19502920539, Email [email protected]: This study aimed to longitudinally investigate the association between circulating neutrophil count and the progression of arterial stiffness and to ascertain whether resting heart rate (RHR) mediates this association.Methods: The current study included 56,760 participants with brachial-ankle pulse wave velocity (baPWV) measurements from a real-life, prospective cohort in China. The associations of circulating neutrophil (exposure) with baseline baPWV, baPWV progression, and arterial stiffness (outcomes), as well as RHR (mediator) were assessed using multivariable linear and Cox regression models and mediation analysis.Results: After adjusting for cardiometabolic risk factors, for each 1-SD increase in neutrophil count, the corresponding increase was 13.5 cm/s (95% CI, 11.1 to 15.9 cm/s, P< 0.001) for the baseline baPWV and 3.10 cm/s (95% CI, 1.51 to 4.69, P< 0.001) for the annual change in baPWV. Over a median follow-up period of 4.08 (IQR: 2.37 to 6.21) years, there were 3,376 incident cases of arterial stiffness among the 23,263 participants. Each 1-SD increase in neutrophil count was associated with a 7% increase in the risk of developing arterial stiffness (HR: 1.07; 95% CI: 1.04 to 1.10, P< 0.001) in the multivariable-adjusted model. In the mediation analyses, 20.0% (95% CI: 16.8% to 24.2%), 12.6% (95% CI: 8.16% to 26.4%), and 16.7% (95% CI: 9.94% to 51.0%) of the observed associations of neutrophil counts with baPWV at baseline, baPWV progression and developing arterial stiffness, respectively, were mediated by RHR.Conclusion: The present study underlines that circulating neutrophil count is significantly associated with arterial stiffness progression and that the RHR is, in part, a mediator of this association.Keywords: arterial stiffness, inflammation, neutrophil count, resting heart rate, mediator, cohort study