Does Poorer Pulmonary Function Accelerate Arterial Stiffening?: A Cohort Study With Repeated Measurements of Carotid-Femoral Pulse Wave Velocity

Abstract

Whether poorer pulmonary function accelerates progression of arterial stiffness remains unknown as prior observational studies have not examined longitudinal changes in arterial stiffness in relation to earlier pulmonary function. Data (N=5342, 26% female) were drawn from the Whitehall II cohort study. Participants completed repeated assessments of forced expiratory volume in 1 second (FEV₁, L) and carotid-femoral pulse wave velocity (cf-PWV, m/s) over 5 years. The effect of FEV₁ on later cf-PWV and its progression was estimated using linear mixed-effects modeling. Possible explanatory mechanisms, such as mediation by low-grade systemic inflammation, common-cause explanation by preexisting cardiometabolic risk factors, and reverse-causation bias, were assessed. Poorer pulmonary function was associated with later higher cf-PWV and its subsequent progression (cf-PWV 5-year change 0.09, 95% CI 0.03-0.17 per SD lower FEV₁) after adjustment for age, sex, ethnicity, heart rate, and mean arterial pressure. Decrease in pulmonary function was associated with later higher cf-PWV (0.17, 95% CI 0.04-0.30 in the top compared to bottom quartile of decline in FEV₁). There was no evidence to support mediation by circulating CRP (C-reactive protein) or IL (interleukin)-6. Furthermore, arterial stiffness was not associated with later FEV₁ after accounting for cardiometabolic status. In conclusion, poorer pulmonary function predicted future arterial stiffness. These findings support pulmonary function as a clinically important risk factor for arterial stiffness and provide justification for future intervention studies for pulmonary function based on its relationship with arterial stiffness.

Keywords: epidemiology; inflammation; longitudinal study; respiratory function.