Abstract

Introduction: Stiffening of the aorta is associated with increased pulse pressure and transmission of pulsatile energy into the cerebral circulation. An association between increased aortic stiffening with intracranial atherosclerotic disease (ICAD) has not been widely studied. We tested the hypothesis that loss of aortic elasticity (i.e. higher aortic stiffness) is associated with a higher presence of ICAD. Methods: ARIC-NCS participants (n=1412; mean age: 76 years; 42% male; 30% Black) with measures of aortic stiffness and vascular brain magnetic resonance imaging (MRI) at the visit 5 (2011-2013) examination were included. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV) using the VP-1000 Plus device (Omron Co., Japan). cfPWV was discretized into high vs. low aortic stiffness based on the upper 25 th percentile, 13.4 m/s. Brain MRI was performed on 3.0 Tesla scanners using a standardized protocol that included an MR angiography (MRA) and high isotropic resolution vessel MRI. Presence of ICAD was defined as eccentric wall thickening with or without luminal stenosis on MRA. We first examined the functional form relationship between continuous measures of cfPWV and ICAD. Comparing those with high vs. low aortic stiffening, we estimated the prevalence odds of ICAD using logistic regression. Models were adjusted for age, sex, race-center, education, smoking, heart rate, blood-pressure lowering medication, diabetes, LDL-cholesterol, and minutes/week of physical activity. Sampling weights were used for generalizability to the full ARIC cohort at visit 5. We tested for effect modification by race, sex, diabetes, central systolic blood pressure, and use of blood pressure-lowering medication. Results: The mean cfPWV was higher among participants with ICAD (12.6 ± 3.2 m/s) compared to those without ICAD (11.2 ± 2.9 m/s). cfPWV was associated with ICAD in a monotonic, linear fashion (p<0.05). The presence of ICAD was 50.6% among participants with high aortic stiffness (cfPWV above the upper 25th percentile; n=354) compared to 30.2% among participants with low aortic stiffness (n=1058). Compared to participants with low aortic stiffness, those with high aortic stiffness had two-fold higher odds of ICAD (odds ratio (OR): 1.97, 95% confidence interval (CI): 1.68, 2.33). No statistically significant modification of this association was observed. Results were robust to exclusions for prevalent stroke (n=43) and prevalent cardiovascular disease (n=153). Conclusions: Aortic stiffness, a highly prevalent trait among older men and women, is associated with ICAD presence quantified by magnetic resonance angiography. Aortic stiffness, its risk factors and the factors associated with the preservation of aortic elasticity, may play a role in modifying the risk of intracranial atherosclerosis.

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