Sex modifies the relationship between age and neurovascular coupling in healthy adults.

Neurovascular coupling (NVC) is the matching between local neuronal activity and regional cerebral blood flow (CBF), but little is known about the effects of age and sex on NVC. This study aimed to investigate the relationships and interaction between age and sex on NVC. Sixty-four healthy adults (18-85 years, N = 34 female) completed a visual stimulus evoked NVC assessment to a flashing checkerboard. NVC responses were measured in the posterior cerebral artery (PCAv) using transcranial Doppler ultrasound. A hierarchical multiple regression was used to determine the relationships between age, sex, and the age by sex interaction on NVC. There was a significant age by sex interaction for baseline (P = 0.001) and peak PCAv (P = 0.01), with a negative relationship with age in females (P < 0.005), and no relationship in males (P ≥ 0.17). NVC responses as a percent increase from baseline showed a significant age by sex interaction (P = 0.014), with a positive relationship with age in females (P = 0.04) and no relationship in males (P = 0.17), even after adjusting for baseline PCAv. These data highlight important sex differences, with an association between age and NVC only apparent in females but not males, and thus a need to account for sex dependent effects of ageing when investigating cerebrovascular regulation.

Comparison of peripheral and cerebral vascular function between premenopausal, early and late postmenopausal females.

NEW FINDINGS: What is the central question of this study? We sought to investigate whether peripheral and cerebrovascular function are impaired in early and late postmenopausal females compared with premenopausal females, while also accounting for nitric oxide and estradiol levels. What is the main finding and its importance? We observed no differences in peripheral vascular and cerebrovascular function between healthy and physically active premenopausal females and early and late postmenopausal females. Our findings contradict previous cross-sectional observations of vascular and cerebrovascular dysfunction across menopause. Longitudinal studies assessing vascular and cerebrovascular outcomes across the menopausal transition are warranted. ABSTRACT: The risk of cardiovascular and cerebrovascular disease increases in ageing females, coinciding with the onset of menopause. Differences in peripheral and cerebrovascular function across menopausal stages, however, are poorly characterized. The aim of this study was to compare peripheral and cerebrovascular function between healthy premenopausal (PRE), early (1-6 years after final menstrual period; E-POST) and late (>6 years after final menstrual period; L-POST) postmenopausal females. We also explored the association between reproductive hormones, NO bioavailability and cerebrovascular function. In 39 females (40-65 years of age), we measured arterial stiffness, brachial artery flow-mediated dilatation, and cerebrovascular reactivity (CVR) to hypercapnia in the middle (MCAv) and internal (ICA) carotid arteries. Follicle-stimulating hormone, estradiol, progesterone and plasma nitrate and nitrite concentrations were also measured. Years since final menstrual period (PRE, 0 ± 0 years; E-POST, 3 ± 1 years; L-POST, 11 ± 4 years; P < 0.001) and estradiol levels (PRE, 145.5 ± 65.6 pg ml-1 ; E-POSTm 30.2 ± 81.2 pg ml-1 ; L-POST, 7.7 ± 11.3 pg ml-1 ; P < 0.001) were different between groups. All groups exceeded the guidelines for recommended physical activity. There were no group differences in blood pressure (P = 0.382), arterial stiffness (P = 0.129), flow-mediated dilatation (P = 0.696) or MCAv CVR (P = 0.442). The ICA CVR blood flow response was lower in PRE compared with L-POST (26.5 ± 19.2 vs. 47.8 ± 12.6%; P = 0.010), but after adjusting for age these differences were no longer present. Flow-mediated dilatation (r = 0.313, P = 0.105) and ICA CVR (r = -0.154, P = 0.495) were not associated with the estradiol concentration. There were no associations between the estradiol concentration and NO bioavailability. These results suggest that in healthy, physically active early and late postmenopausal females, vascular and cerebrovascular function is generally well preserved.

The relationships between age, sex, and cerebrovascular reactivity to hypercapnia using traditional and kinetic-based analyses in healthy adults.

The effect of age and sex on intracranial and extracranial cerebrovascular function is poorly understood. We investigated the relationships between age, sex, and cerebrovascular reactivity (CVR) to hypercapnia in 73 healthy adults (18-80 yr, n = 39 female). CVR to hypercapnia was assessed in the middle cerebral artery (MCA) using transcranial Doppler ultrasound and at the internal carotid artery (ICA) using duplex ultrasound. MCA CVR was characterized by peak MCA velocity (MCAv) response per mmHg increase in end-tidal CO2 and by using a monoexponential model to characterize the kinetics (time constant) of the MCAv response. ICA reactivity was assessed as the relative peak increase in artery diameter. Hierarchical multiple regression determined the relationships between age, sex, and the age-by-sex interaction on all baseline and CVR outcomes. There was no relationship between ICA reactivity (%) with age (P = 0.07), sex (P = 0.56), or a moderator effect of sex on the age effect (P = 0.24). MCAv CVR showed no relationship with age (P = 0.59), sex (P = 0.09), or an age-by-sex moderator effect (P = 0.90). We observed a positive relationship of MCAv CVR time constant with age (P = 0.013), such that the speed of the MCA response was slower with advancing age. The present study provides comprehensive data on age- and sex-specific relationships with intracranial and extracranial cerebrovascular responses to hypercapnia. Despite similar MCAv CVR and ICA reactivity between sexes, kinetic responses of the MCA revealed a slower rate of adjustment with advancing age.NEW & NOTEWORTHY We observed similar MCA CVR and ICA reactivity in males and females. However, kinetic responses of the MCA to hypercapnia suggest that advancing age slows down the rate at which MCA velocity increases in response to hypercapnia. These data indicate distinct regulatory differences, and an impaired vasomotor control of the cerebrovasculature with advancing age, not detected by traditional methods.

Effect of menopause on cerebral artery blood flow velocity and cerebrovascular reactivity: Systematic review and meta-analysis.

BACKGROUND: Menopause and its associated decline in oestrogen is linked to chronic conditions like cardiovascular disease and osteoporosis, which may be difficult to disentangle from the effects of ageing. Further, post-menopausal women are at increased risk of cerebrovascular disease, linked to declines in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), yet the direct understanding of the impact of the menopause on cerebrovascular function is unclear. The aim of this systematic review and meta-analysis was to examine the literature investigating CBF and CVR in pre- compared with post-menopausal women METHODS: Five databases were searched for studies assessing CBF or CVR in pre- and post-menopausal women. Meta-analysis examined the effect of menopausal status on middle cerebral artery velocity (MCAv), and GRADE-assessed evidence certainty RESULTS: Nine studies (n=504) included cerebrovascular outcomes. Six studies (n=239) reported negligible differences in MCAv between pre- and post-menopausal women [2.11cm/s (95% CI: -8.94 to 4.73, p=0.54)], but with a "low" certainty of evidence. MCAv was lower in post-menopausal women in two studies, when MCAv was adjusted for blood pressure. CVR was lower in post- compared with pre-menopausal women in two of three studies, but high-quality evidence is lacking. Across outcomes, study methodology and reporting criteria for menopause were inconsistent CONCLUSIONS: MCAv was similar in post- compared with pre-menopausal women. Methodological differences in characterising menopause and inconsistent reporting of cerebrovascular outcomes make comparisons difficult. Comprehensive assessments of cerebrovascular function of the intra- and extracranial arteries to determine the physiological implications of menopause on CBF with healthy ageing is warranted.

The effect of heat therapy on blood pressure and peripheral vascular function: A systematic review and meta-analysis.

NEW FINDINGS: What is the topic of this review? We have conducted a systematic review and meta-analysis on the current evidence for the effect of heat therapy on blood pressure and vascular function. What advances does it highlight? We found that heat therapy reduced mean arterial, systolic and diastolic blood pressure. We also observed that heat therapy improved vascular function, as assessed via brachial artery flow-mediated dilatation. Our results suggest that heat therapy is a promising therapeutic tool that should be optimized further, via mode and dose, for the prevention and treatment of cardiovascular disease risk factors. ABSTRACT: Lifelong sauna exposure is associated with reduced cardiovascular disease risk. Recent studies have investigated the effect of heat therapy on markers of cardiovascular health. We aimed to conduct a systematic review with meta-analysis to determine the effects of heat therapy on blood pressure and indices of vascular function in healthy and clinical populations. Four databases were searched up to September 2020 for studies investigating heat therapy on outcomes including blood pressure and vascular function. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. A total of 4522 titles were screened, and 15 studies were included. Healthy and clinical populations were included. Heat exposure was for 30-90 min, over 10-36 sessions. Compared with control conditions, heat therapy reduced mean arterial pressure [n = 4 studies; mean difference (MD): -5.86 mmHg, 95% confidence interval (CI): -8.63, -3.10; P < 0.0001], systolic blood pressure (n = 10; MD: -3.94 mmHg, 95% CI: -7.22, -0.67; P = 0.02) and diastolic blood pressure (n = 9; MD: -3.88 mmHg, 95% CI: -6.13, -1.63; P = 0.0007) and improved flow-mediated dilatation (n = 5; MD: 1.95%, 95% CI: 0.14, 3.76; P = 0.03). Resting heart rate was unchanged (n = 10; MD: -1.25 beats/min; 95% CI: -3.20, 0.70; P = 0.21). Early evidence also suggests benefits for arterial stiffness and cutaneous microvascular function. The certainty of evidence was moderate for the effect of heat therapy on systolic and diastolic blood pressure and heart rate and low for the effect of heat therapy on mean arterial pressure and flow-mediated dilatation. Heat therapy is an effective therapeutic tool to reduce blood pressure and improve macrovascular function. Future research should aim to optimize heat therapy, including the mode and dose, for the prevention and management of cardiovascular disease.