Role of Inflammatory Markers in the Progression of Arterial Stiffness and Mortality: A Multicenter Longitudinal Cohort Study

Background Inflammation is a well‐known driver of cardiovascular disease, but its role in the progression of arterial stiffness remains incompletely defined. Methods Individuals undergoing brachial‐ankle pulse wave velocity (baPWV) measurements as part of a generalized health examination were identified from a multicenter registry. Cross‐sectional and longitudinal associations of white blood cell (WBC) counts and hsCRP (high‐sensitivity C‐reactive protein) with baPWV were evaluated using multivariable regression models. The association between WBC counts and all‐cause mortality was assessed using multivariable Cox regression, and mediation analysis using a counterfactual framework quantified the indirect effect of WBC counts through baPWV. Results A total of 9517 individuals (median age 52 years, 74.5% men) were included. Both WBC counts and hsCRP were positively associated with higher baPWV (both P <0.001). Among 2347 participants with follow‐up measurements (median interval 2.4 years), WBC counts were independently associated with faster baPWV progression (adjusted β‐coefficient per 10 9 /L, 2.59; 95% CI, 1.38–3.76; P <0.001), whereas hsCRP had a borderline association with baPWV progression ( P =0.047) which was attenuated after adjustment for WBC counts ( P =0.284). During a median follow‐up of 3.7 years, higher WBC counts were significantly associated with increased all‐cause mortality (adjusted hazard ratio, 1.180; 95% CI, 1.009–1.380; P =0.038). Mediation analysis indicated that 7.9% (95% CI, 0.2–15.7%; P =0.043) of this association was explained by higher baPWV. Conclusions Higher WBC counts are associated with greater arterial stiffness measured by baPWV, and a modest proportion of the mortality risk related to elevated WBC counts appears to be mediated through increased arterial stiffness.