Carotid Artery Stiffness Mechanisms Are Associated With End Organ Damage and All-Cause Mortality: MESA (Multi-Ethnic Study of Atherosclerosis)

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.

Keywords: chronic kidney disease; dementia; end organ damage; vascular stiffness.

Figure 1. Graphical representation of methods used to differentiate structural and load‐dependent stiffness.,

A, Total stiffness is calculated from measured pressure and diameter. B, A participant‐specific model of arterial mechanics is fitted. C, Structural stiffness is calculated from pressure and diameter adjusted to 120/80 mm Hg. D, Load‐dependent stiffness is calculated as the difference of total and structural stiffness. Representative results are shown for 2 participants (one in red, one in black) who had similar total carotid pulse wave velocity (cPWV) (6.4 vs 6.3 m/s) but via different mechanisms. One participant (red dashed lines and text) had higher structural cPWV (7.6 vs 6.0 mm Hg), whereas the other participant (black solid lines and font) had higher load‐dependent cPWV (0.4 vs −1.3 mm Hg).

Figure 2. Unadjusted Kaplan–Meier curves (with 95% CIs) for (A) all‐cause mortality, (B) chronic kidney disease, and (C) dementia.

Kaplan–Meier curves show that incidence of all‐cause mortality and dementia is greater for participants with high structural versus high load‐dependent stiffness, whereas incidence of chronic kidney disease is greater for participants with high load‐dependent stiffness.

Figure 3. Higher total cPWV and structural cPWV were associated with all‐cause mortality.

Higher load‐dependent cPWV was associated with chronic kidney disease, and higher total cPWV was associated with dementia. Hazard ratios (with 95% CIs) per 1 m/s increment cPWV were calculated from the most fully adjusted Cox model, Demographic covariates: age, sex, race or ethnicity, study site, education level; risk factor covariates: body mass index, diabetes status, smoking status, smoking pack‐years, systolic blood pressure, non‐high‐density lipoprotein cholesterol, antihypertensive medication usage, lipid lowering medication usage. CKD indicates chronic kidney disease; cPWV, carotid pulse wave velocity; and Load‐dep., load‐dependent.