title: Peripheral and Cerebrovascular Function during the Female Lifespan
Creators: name: Brislane, A
Publisher: name: Liverpool John Moores University
Year: 2021

description: The female hormone oestrogen is thought to influence vascular physiology throughout the female lifespan particularly during life events such as menopause and pregnancy. The rapid decline in oestrogen during the menopause is associated with increased cardiovascular (CV) risk, potentially via reduced vascular function. Moreover pregnancy, where oestrogen is elevated for a prolonged period, is a time of profound physiological upheaval including large CV adaptations. Nonetheless, the impact of these important events in the female life course on cerebral and peripheral vascular risk is largely unknown and developing an understanding of such vascular responses is necessary. Importantly, exercise training has known benefits on cerebral and peripheral vascular function, however the role of exercise and physical activity (PA) in pregnancy and menopausal vascular adaptation is poorly defined. Moreover, maternal health has shown to program foetal health in-utero and is associated with immediate and long-term effects on offspring into adulthood and even in subsequent generations. Pregnancy exercise may therefore translate to the neonatal environment, although this has yet to be defined in humans. The aim of this thesis was to describe the cerebral and peripheral vascular changes that are associated with menopause and to assess the impact of exercise training during pregnancy on maternal and offspring vascular health. In a cross-sectional design study, 50 pre-menopausal (PRE-M; 33.29.1years) and 50 post-menopausal (POST-M; 58.55.5years) women underwent assessment of brain blood flow assessed via middle cerebral artery velocity (MCAv), cerebrovascular reactivity (CBV-R) and cerebral autoregulation. Peripheral vascular function (brachial and femoral artery endothelial function via flow mediated dilation (FMD)) and structure (brachial (b), femoral (f) and carotid (c) intima-media thickness (IMT) and pulse wave velocity (PWV)) were also assessed. Cardiorespiratory fitness was determined by a maximal oxygen consumption test (VO2max) and objective measures of PA and sedentary behaviour were made. All PRE-M and POST-M women were compared followed by a sub-analysis that included women close to- (Late-PRE-M, N=10) and within 5 years of menopause (Early-POST-M, N=10). POST-M women engaged in significantly less vigorous PA (5 [3, 7 min/d]) compared to PRE-M women (9 [7, 11 min/d] p=0.01) and had a lower cardiorespiratory fitness (24.8 [22.6, 26.9 ml·kg·min]) compared to PRE-M women (34.7 [32.6, 36.9 ml·kg·min] p&lt;0.001). Early-POST-M ii women engaged in significantly less light PA (354 [292, 415 min/d]) compared to Late-PRE-M women (264 [199, 329 min/d] p=0.05). There were no differences between PRE- or POST-M women for absolute CBV-R (p=0.52), relative CBV-R (p=0.18) or parameters of cerebral autoregulation including normalized gain (p=0.56) or phase in the low frequency (p=0.73). In the sub analysis, there were no differences between groups for absolute CBV-R (p=0.79), relative CBV-R (p=0.99), normalized gain (p=0.77) or phase (p=0.18) in the low frequency. POST-M women had lower brachial FMD (4.1 [2.9, 5.2 %]) compared to PRE-M women (6.4 [5.4, 7.5%] p=0.004) and a lower femoral FMD 2.8% [1.9, 3.6 %]) compared to PRE-M women (5.8 [4.9, 6.7 %] p&lt;0.001). POST-M women also had a higher PWV (6.87 [6.5, 7.3 m/s]) compare to PRE-M women (5.45 [5.1, 5.8 m/s] p&lt;0.001) compared to PRE-M. Only femoral FMD was lower in Early-POST-M women (2.1% [0.8, 3.5 %]) compared to Late-PRE-M women (4.1 [2.7, 5.5 %] p=0.049). Menopause was associated with higher carotid artery lumen diameter (p=0.01), as well as higher IMT at the carotid (0.70 [0.68, 0.73 mm] p&lt;0.001), brachial (0.38 [0.36, 0.41mm] p=0.001) and femoral arteries (0.49 [0.46, 0.53 mm] p&lt;0.001). Only cIMT (0.67 [0.63, 0.63 mm]) compared to Late-PRE-M women (0.59 [0.54, 0.65 mm] p=0.03). In summary, menopause is associated with lower MCAv, impaired central and peripheral vascular function and greater artery wall thickness compared to the PRE-M state. These decrements are not all present in early menopause suggesting that the duration of time from menopause and age may have a greater effect on these parameters than the event of menopause alone. Finally, our data provides some evidence that post-menopausal vascular decline may be partly driven by reductions in vigorous PA and/or cardiorespiratory fitness. Twenty-one healthy pregnant women were recruited in trimester 1 (T1) to a partially supervised exercise (EX) or control (CONT) group. Women underwent assessment of cerebrovascular and peripheral vascular function and structural measurements at the end of T1, trimester 2 (T2), and trimester 3 (T3). Participants performed a submaximal exercise test and PA and sedentary behavior objectively monitored for 7 days at each trimester. The exercise intervention comprised of 3-4 sessions per week starting with 15-minutes progressing to 30-minutes at 60-70% maximum heart rate as per the Royal College of Obstetrics and Gynaecology (RCOG) guidelines. MCAv reduced significantly during pregnancy (-8 cm/s-1 [-14, -2 cm/s]; main effect of time p=0.02). There was a trend for normalised gain in the low frequency domain to increase during pregnancy (1.6% [1.5, 1.7%]; main effect of time p=0.08). There was a trend for an effect of time for increased phase in the low frequency (13.9° [29°, 39°]; main effect of time p=0.06). Femoral artery FMD decreased during pregnancy (3.5% [-6.5, -0.5%]; iii main effect of time p=0.03). Brachial artery diameter increased during pregnancy (0.03cm [0.01, 0.06 cm]; main effect of time p=0.03). Carotid artery diameter increased during pregnancy (0.33mm [0.07, 0.58 mm]; main effect of time p=0.04). There was a trend for a reduced PWV during pregnancy (5.01 m/s [2.8, 7.2 cm/s]; main effect of time p=0.09). However, PWV was significantly greater in the EX group (5.3 m/s [1.6, 8.9 m/s] compared to the CONT group (4.7m/s [3.0, 6.5 m/s]; main effect of intervention p=0.04). There was no time*intervention effect for PWV (p=0.68). No other intervention effects were apparent. In summary, pregnancy results in reduced MCAv, possibly due to reduced vascular resistance (carotid artery enlargement) and altered cerebral autoregulation. Pregnancy also results in increased systemic conduit artery size and a reduction in femoral FMD; changes that are seemingly unaffected by adhering to pregnancy exercise guidelines as recommended by the RCOG. In study 3 offspring cIMT, delivery outcomes and maternal quality of life (QOL) were assessed in the women recruited for study 2. Although not significant, compared to the control group, the offspring of the EX group (N=7) had a smaller IMT (EX; 0.45±0.06mm; CONT; 0.49±0.07mm, p=0.27) and IMT/Lumen (EX; 0.15±0.02, CONT; 0.17±0.04, p=0.19) compared to the control group (N=11). The EX group also had a larger yet non-significant carotid lumen diameter (EX; 2.92±0.13, CONT; 2.88±0.40, p=0.82). Delivery outcomes and maternal QOL were unaffected by exercise. This pilot data suggests that maternal exercise participation may have some role in programming progeny vascular structure the vasculature but does not appear critical to influencing delivery outcomes or post-partum QOL.