Abstract

Background: Cerebral hemodynamic dysfunction is associated with brain small artery disease and poorer cognition. With aging, systemic arteries stiffen, magnifying the spread of pulsatility to distal organs. The brain is especially susceptible to pulsatility due to low impedance to flow. Increased pulsatility causes abnormal brain arteriolar remodeling in animal models. Therefore, we hypothesize that measures of aortic stiffness relate to poorer cerebral autoregulation, an in-vivo measure of arteriolar function. Methods: We recruited participants in the Washington Heights-Inwood Community Aging Project for this study. For autoregulation, both middle cerebral arteries were insonated at a depth of 50-58 mm. End-tidal CO2 (EtCO2) was measured continuously with a facemask. After ten minutes of baseline recording, a mixture of air enriched with 5% CO2 was administered through the facemask for 2 minutes. Cerebrovascular reactivity was calculated as % change in mean CBFV (mCBFV) per 1 mm increase in mean EtCO2 during CO2 inhalation. We averaged the right and left CO2 reactivity percentage. For aortic stiffness, we acquired carotid-femoral pulse wave velocity (cfPWV) with non-invasive oscillometry using the Vicorder system (Skidmore Medical Limited, Bristol, UK). We used generalized linear model to obtain beta estimates of the association between CO2 reactivity and cfPWV. Results: We included 158 participants (mean age 77±6.4 years, 67% women, 40% non-Hispanic black, 38% non-Hispanic white, and 20% Hispanic). Hypertension was present in 54% of the participants. cfPWV was associated with poorer CO2 reactivity (B=-0.038, P=0.047), independent of age, sex, ethnicity, and hypertension. Brachial pulse pressure (B=0.007, P=0.38) and mean arterial pressure (B=-0.017, P=0.21) were not associated with CO2 reactivity, and adding brachial pulse pressure and mean arterial pressure to the adjusted model did not change the association between cfPWV and poorer CO2 reactivity. Conclusions: Aortic stiffness is associated with poorer CO2 reactivity independent of traditional measures of hypertension, a marker of cerebral autoregulation and arteriolar health. Poorer CO2 reactivity may mediate the reported effects of aortic stiffness on brain outcomes.

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