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

Objective: 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.