Atrial fibrillation (AF) and hypertension (HTN) are both associated with impaired cerebrovascular carbon dioxide reactivity (CVR<sub>CO2</sub>), an indicator of cerebral vasodilatory reserve. We hypothesised that CVR<sub>CO2</sub> would be lower in patients with both AF and HTN (AF + HTN) compared to normotensive AF patients, due to an additive effect of AF and HTN on CVR<sub>CO2</sub>. Forty AF (68 ± 9 years) and fifty-seven AF + HTN (68 ± 8 years) patients underwent transcranial Doppler ultrasound measurement of middle cerebral artery blood velocity (MCA V<sub>m</sub>) during stepped increases and decreases in end-tidal carbon dioxide (P<sub>ET</sub>CO<sub>2</sub>). A cerebrovascular conductance index (CVCi) was calculated as the ratio of MCA V<sub>m</sub> and mean arterial pressure (MAP). CVR<sub>CO2</sub> was determined from the linear slope for MCA V<sub>m</sub> and MCA CVCi vs P<sub>ET</sub>CO<sub>2</sub>. Baseline MAP was higher in AF + HTN than AF (107 ± 9 vs. 98 ± 9 mmHg, respectively; p < 0.001), while MCA V<sub>m</sub> was not different (AF + HTN:49.6 [44.1-69.0]; AF:51.7 [45.2-63.3] cm.s<sup>-1</sup>; p = 0.075), and CVCi was lower in AF + HTN (0.46 [0.42-0.57] vs. 0.54 [0.44-0.63] cm.s<sup>-1</sup>.mmHg<sup>-1</sup>; p < 0.001). MCA V<sub>m</sub> CVR<sub>CO2</sub> was not different (AF + HTN: 1.70 [1.47-2.19]; AF 1.74 [1.54-2.52] cm/s/mmHg<sup>-2</sup>; p = 0.221), while CVCi CVR<sub>CO2</sub> was 13% lower in AF + HTN (0.013 ± 0.004 vs 0.015 ± 0.005 cm.s<sup>-1</sup>.mmHg<sup>-1</sup>; p = 0.047). Our results demonstrate blunted cerebral vasodilatory reserve (determined as MCA CVCi CVR<sub>CO2</sub>) in AF + HTN compared to AF alone. This may implicate HTN as a driver of further cerebrovascular dysfunction in AF that may be important for the development of AF-related cerebrovascular events and downstream cognitive decline. We demonstrated reduced cerebrovascular CO<sub>2</sub> responsiveness in atrial fibrillation with hypertension (AF+HTN) vs. atrial fibrillation (AF). Furthermore, AF per se (as opposed to normal sinus rhythm) predicts reduced cerebrovascular CO<sub>2</sub> responsiveness. Our findings suggest additional cerebrovascular dysfunction in AF+HTN vs. AF.
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