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 109/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.