Abstract
Background Arterial stiffness can be separated into 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between stiffness mechanisms and end organ damage is unknown. Methods and Results MESA (Multi-Ethnic Study of Atherosclerosis) participants with carotid ultrasound were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mm Hg blood pressure with participant-specific models. Load-dependent stiffness was the difference of total and structural stiffness. Associations with incident chronic kidney disease (CKD), dementia, and mortality were assessed with adjusted Cox models. During 14.3±4.8 years of follow-up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (hazard ratio [HR], per 1 m/s, 1.04 [95% CI, 1.01-1.08], P=0.02) and dementia (HR, 1.06 [95% CI, 1.01-1.12], P=0.03) but not CKD (HR, 1.03 [95% CI, 0.98-1.08], P=0.33). Structural cPWV was significantly associated with mortality (HR, 1.04 [95% CI, 1.00-1.08], P=0.04) but not CKD (HR, 1.00 [95% CI, 0.94-1.05], P=0.86) or dementia (HR, 1.06 [95% CI, 0.99-1.13], P=0.06). Load-dependent cPWV was significantly associated with CKD (HR, 1.38 [95% CI, 1.17-1.63], P<0.001) but not mortality (HR, 1.11 [95% CI, 0.99-1.25], P=0.07) or dementia (HR, 1.14 [95% CI, 0.94-1.38], P=0.19). Conclusions The mechanisms of arterial stiffness were associated with all-cause mortality and CKD. Structural stiffness was associated with all-cause mortality, and load-dependent stiffness was associated with CKD. Total stiffness was associated with dementia but load-dependent and structural stiffness were not.