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Profiling cerebrovascular function in migraine: A systematic review and meta-analysis.
Dzator, JS, Howe, PR, Wong, RH
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2021;(5):919-944
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Abstract
Previous studies have investigated whether migraine is a circulatory disorder, as migraineurs are at heightened risk of cerebrovascular disease. However, in most cases, systemic vascular function was evaluated, which may not reflect abnormalities in the cerebral circulation. Therefore, we aimed to determine whether cerebrovascular function differs between migraineurs and controls. A systematic literature search was conducted across three electronic databases to search for studies that compared cerebrovascular function in migraineurs to controls. Where applicable, meta-analyses were used to determine standardised mean differences (SMD) between migraineurs and controls. Seventy articles were identified, 40 of which contained quantitative data. Meta-analyses showed pulsatility index (PI) was higher (SMD = 0.23; 95%CI = 0.05 to 0.42, P = 0.01) and cerebrovascular responsiveness (CVR) to hypercapnia was lower (SMD=-0.34; 95%CI=-0.67 to -0.01, P = 0.04) in the posterior circulation of migraineurs, particularly those without aura. The meta-analyses also indicated that migraineurs have higher resting mean blood flow velocity in both anterior (SMD = 0.14; 95%CI = 0.05 to 0.23, P = 0.003) and posterior circulations (SMD = 0.20; 95%CI = 0.05 to 0.34, P = 0.007). Compared to healthy controls, migraineurs have altered cerebrovascular function, evidenced by elevated PI (representing arterial stiffness) and impaired CVR to hypercapnia (representing cerebral vasodilator function). Future studies should investigate whether improvement of cerebrovascular function is able to alleviate migraine.
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Effects of cardiorespiratory fitness and exercise training on cerebrovascular blood flow and reactivity: a systematic review with meta-analyses.
Smith, EC, Pizzey, FK, Askew, CD, Mielke, GI, Ainslie, PN, Coombes, JS, Bailey, TG
American journal of physiology. Heart and circulatory physiology. 2021;(1):H59-H76
Abstract
We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations.NEW & NOTEWORTHY Higher cardiorespiratory fitness is associated with lower cerebrovascular resistance and elevated cerebrovascular reactivity at rest. Only adults with a true-high fitness based on normative data exhibited elevated middle cerebral artery velocity. The positive effect of higher compared with lower cardiorespiratory fitness on resting cerebrovascular resistance was more evident in male-only studies when compared with mixed or female-only studies. A period of exercise training resulted in negligible changes in middle cerebral artery velocity and global cerebral blood flow, with potential for improvements in cerebrovascular reactivity.
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Effect of menopause on cerebral artery blood flow velocity and cerebrovascular reactivity: Systematic review and meta-analysis.
Ruediger, SL, Koep, JL, Keating, SE, Pizzey, FK, Coombes, JS, Bailey, TG
Maturitas. 2021;:24-32
Abstract
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.
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Effects of inorganic nitrate and nitrite consumption on cognitive function and cerebral blood flow: A systematic review and meta-analysis of randomized clinical trials.
Clifford, T, Babateen, A, Shannon, OM, Capper, T, Ashor, A, Stephan, B, Robinson, L, O'Hara, JP, Mathers, JC, Stevenson, E, et al
Critical reviews in food science and nutrition. 2019;(15):2400-2410
Abstract
We conducted a systematic review and meta-analysis of randomized clinical trials examining the effect of inorganic nitrate or nitrite supplementation on cognitive function (CF) and cerebral blood flow (CBF). Two databases (PubMed, Embase) were searched for articles from inception until May 2017. Inclusion criteria were: randomized clinical trials; participants >18 years old; trials comparing a nitrate/nitrite intervention with a control. Thirteen and nine trials were included in the meta-analysis to assess CF and CBF, respectively. Random-effects models were used and the effect size described as standardized mean differences (SMDs). A total of 297 participants (median of 23 per trial) were included for CF; 163 participants (median of 16 per trial) were included for CBF. Nitrate/nitrite supplementation did not influence CF (SMD +0.06, 95% CI: -0.06, 0.18, P = 0.32) or CBF under resting (SMD +0.14, 95% CI: -0.13, 0.41, P = 0.31), or stimulated conditions (SMD + 0.23, 95% CI: -0.11, 0.56, P = 0.19). The meta-regression showed an inverse association between duration of the intervention and CBF (P = 0.02) but no influence of age, BMI or dose (P < 0.05). Nitrate and nitrite supplementation did not modify CBF or CF. Further trials employing larger samples sizes and interventions with longer duration are warranted.
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Effect of antihypertensive agents on cerebral blood flow and flow velocity in acute ischaemic stroke: systematic review of controlled studies.
Sare, GM, Gray, LJ, Bath, PM
Journal of hypertension. 2008;(6):1058-64
Abstract
OBJECTIVE High blood pressure is common in acute stroke and is associated independently with poor outcome. Lowering blood pressure might improve outcome, provided it does not reduce cerebral blood flow in the presence of dysfunctional cerebral autoregulation. METHODS We performed a systematic review of clinical controlled trials that administered antihypertensive agents within 7 days of ischaemic stroke and measured cerebral blood flow or cerebral blood flow velocity. RESULTS From 74 identified publications, 11 trials met the criteria. A variety of antihypertensive agents were used: angiotensin-converting enzyme inhibitors (three trials), angiotensin-receptor antagonists (one), calcium antagonists (five), diuretics (one) and nitrates (two). The trials' median quality score was 2.5/5, and the studies used single photon emission computed tomography (five trials), xenon-computed tomography (three) and positron emission tomography (one) for determining cerebral blood flow, and transcranial Doppler (six) for measuring flow velocity. Analysis of randomized controlled trials revealed no alteration in cerebral blood flow for any antihypertensive agent. Nonrandomized trials that assessed blood flow before and after administration of the agents showed an increase in blood flow for calcium channel blockers (standardized mean difference 0.43, 95% confidence interval 0.01-0.85). CONCLUSION There are few quality studies assessing the effect of antihypertensive agents on cerebral blood flow and flow velocity, and variability in reporting make meta-analysis difficult. However, there is little existing evidence that antihypertensive agents reduce cerebral blood flow in spite of their effects on lowering blood pressure.