Kruse, Sarah

Cerebrovascular reactivity to hypercapnia is higher in women receiving menopausal hormone therapy (MHT) compared with controls, and this may persist after cessation of MHT. We hypothesized that the effect of MHT may be influenced by mean arterial pressure (MAP). Therefore, we examined both middle cerebral artery velocity (MCAv) and MAP responses to stepped hypercapnia in 60 postmenopausal women who were previously randomized to receive oral conjugated equine estrogen (oCEE, n=15), transdermal 17β estradiol (tE2, n=22), or placebo (PLA, n=23) for 4 years. After a 3 year washout period, reactivity was calculated from the slope of the relationship between MCAv or MAP and end‐tidal CO 2 . MCAv reactivity was higher in the oCEE group compared with the PLA group (1.6±0.2 vs. 1.1±0.1 cm/s/mmHg; oCEE vs. PLA, respectively, p<0.05), but similar between the tE2 and PLA group (1.3±0.2 vs. 1.1±0.1 cm/s/mmHg; tE2 vs. PLA, respectively, p>0.05). There were no significant differences in MAP reactivity (1.0±0.2, 0.6±0.1, 0.7±0.2 mmHg/mmHg of CO 2 , oCEE vs. tE2 vs. PLA, respectively, p>0.05) among the groups. However, in the combined MHT group, MAP reactivity was positively correlated with MCAv reactivity (r=0.58, p<0.001), such that women with higher MAP responses demonstrate greater MCAv responses to hypercapnia. In conclusion, there were no differences in MAP reactivity 3 years after cessation of MHT. In addition, our results suggest that greater cerebrovascular reactivity in postmenopausal women who received MHT may be driven by augmented blood pressure responses to hypercapnia. Funding: K99 HL 118164, AG 044170 and HL 83947.

Common carotid artery (CA) and middle cerebral artery (MCA) blood flow are controlled by multiple factors to ensure that the brain receives adequate blood supply. Additionally, CA arterial stiffness may affect blood flow regulation. The purpose of this study was to investigate the effect of cyclooxygenase (COX) inhibition on arterial stiffness and the relationship between CA and MCA blood flow in young (26±5y) and older (66±7y) adults to determine if aging modifies this relationship. While baseline CA flow and flow velocity were similar between groups, baseline MCA flow velocity was greater in young (59±6 cm/s) compared to older (40±4 cm/s) adults (p<0.05). During COX inhibition, CA flow, CA flow velocity and MCA flow velocity decreased from baseline in young (∆: ‐116±35 mL/min, ‐6±1 cm/s, ‐23±5 cm/s; respectively) and older adults (∆: ‐153±40 mL/min, ‐5±1 cm/s, ‐11±2 cm/s; respectively). The association between CA flow velocity and MCA flow velocity was altered by COX inhibition (r=0.60 vs. r=0.15). β‐stiffness was higher in older compared to young adults (13±2 vs. 5±1 AU; p<0.05). Among older adults, there was a trend for COX inhibition to increase β‐stiffness. Our results suggest that CA and MCA blood flow are regulated differently and that COX inhibition alters the correlation between CA and MCA blood flow. Therefore, it may be incorrect to assume that CA flow is a surrogate measurement for cerebral blood flow.