The impact of age, sex, cardio-respiratory fitness, and cardiovascular disease risk on dynamic cerebral autoregulation and baroreflex sensitivity

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Abstract

Background

Humans display an age-related decline in cerebral blood flow and increase in blood pressure (BP), but changes in the underlying control mechanisms across the lifespan are less well understood. We aimed to; (1) examine the impact of age, sex, cardiovascular disease (CVD) risk, and cardio-respiratory fitness on dynamic cerebral autoregulation and cardiac baroreflex sensitivity, and (2) explore the relationships between dynamic cerebral autoregulation (dCA) and cardiac baroreflex sensitivity (cBRS).

Methods

206 participants aged 18–70 years were stratified into age categories. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound. Repeated squat-stand manoeuvres were performed (0.10 Hz), and transfer function analysis was used to assess dCA and cBRS. Multivariable linear regression was used to examine the influence of age, sex, CVD risk, and cardio-respiratory fitness on dCA and cBRS. Linear models determined the relationship between dCA and cBRS.

Results

Age, sex, CVD risk, and cardio-respiratory fitness did not impact dCA normalised gain, phase, or coherence with minimal change in all models ( P > 0.05). cBRS gain was attenuated with age when adjusted for sex and CVD risk (young–older; β = − 2.86 P < 0.001) along with cBRS phase (young–older; β = − 0.44, P < 0.001). There was no correlation between dCA normalised gain and phase with either parameter of cBRS.

Conclusion

Ageing was associated with a decreased cBRS, but dCA appears to remain unchanged. Additionally, our data suggest that sex, CVD risk, and cardio-respiratory fitness have little effect.

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Most cited references 56

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Stroke Risk Factors, Genetics, and Prevention.

Amelia K. Boehme, Charles Esenwa, Mitchell S. V. Elkind (2017)

Stroke is a heterogeneous syndrome, and determining risk factors and treatment depends on the specific pathogenesis of stroke. Risk factors for stroke can be categorized as modifiable and nonmodifiable. Age, sex, and race/ethnicity are nonmodifiable risk factors for both ischemic and hemorrhagic stroke, while hypertension, smoking, diet, and physical inactivity are among some of the more commonly reported modifiable risk factors. More recently described risk factors and triggers of stroke include inflammatory disorders, infection, pollution, and cardiac atrial disorders independent of atrial fibrillation. Single-gene disorders may cause rare, hereditary disorders for which stroke is a primary manifestation. Recent research also suggests that common and rare genetic polymorphisms can influence risk of more common causes of stroke, due to both other risk factors and specific stroke mechanisms, such as atrial fibrillation. Genetic factors, particularly those with environmental interactions, may be more modifiable than previously recognized. Stroke prevention has generally focused on modifiable risk factors. Lifestyle and behavioral modification, such as dietary changes or smoking cessation, not only reduces stroke risk, but also reduces the risk of other cardiovascular diseases. Other prevention strategies include identifying and treating medical conditions, such as hypertension and diabetes, that increase stroke risk. Recent research into risk factors and genetics of stroke has not only identified those at risk for stroke but also identified ways to target at-risk populations for stroke prevention.

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Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies

M R Law, J K Morris, N Wald (2009)

Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.

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Cerebral autoregulation dynamics in humans.

K Lindegaard, H Nornes, W. Sorteberg … (1988)

We studied the response of cerebral blood flow to acute step decreases in arterial blood pressure noninvasively and nonpharmacologically in 10 normal volunteers during normocapnia, hypocapnia, and hypercapnia. The step (approximately 20 mm Hg) was induced by rapidly deflating thigh blood pressure cuffs following a 2-minute inflation above systolic blood pressure. Instantaneous arterial blood pressure was measured by a new servo-cuff method, and cerebral blood flow changes were assessed by transcranial Doppler recording of middle cerebral artery blood flow velocity. In hypocapnia, full restoration of blood flow to the pretest level was seen as early as 4.1 seconds after the step decrease in blood pressure, while the response was slower in normocapnia and hypercapnia. The time course of cerebrovascular resistance was calculated from blood pressure and blood flow recordings, and rate of regulation was determined as the normalized change in cerebrovascular resistance per second during 2.5 seconds just after the step decrease in blood pressure. The reference for normalization was the calculated change in cerebrovascular resistance that would have nullified the effects of the step decrease in arterial blood pressure on cerebral blood flow. The rate of regulation was 0.38, 0.20, and 0.11/sec in hypocapnia, normocapnia, and hypercapnia, respectively. There was a highly significant inverse relation between rate of regulation and PaCO2 (p less than 0.001), indicating that the response rate of cerebral autoregulation in awake normal humans is profoundly dependent on vascular tone.

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Author and article information

Contributors

Joseph D. Maxwell: Joseph.Maxwell@mft.nhs.uk

Daniel J. Bannell: D.Bannell@2015.ljmu.ac.uk

Aine Brislane: A.Brislane@yorksj.ac.uk

Sophie E. Carter: S.Carter@yorksj.ac.uk

Gemma D. Miller: G.D.Miller@ljmu.ac.uk

Kirsty A. Roberts: K.A.Roberts@ljmu.ac.uk

Nicola D. Hopkins: N.D.Hopkins@ljmu.ac.uk

David A. Low: D.A.Low@ljmu.ac.uk

Howard H. Carter: mhcarter10@gmail.com

Andrew Thompson: Andrew.Thompson@liverpool.ac.uk

Jurgen A. H. R. Claassen: Jurgen.Claassen@radboudumc.nl

Dick H. J. Thijssen: Dick.Thijssen@radboudumc.nl

Helen Jones:

ORCID: http://orcid.org/0000-0001-8282-1459

H.Jones1@ljmu.ac.uk

Journal

Journal ID (nlm-ta): Eur J Appl Physiol

Journal ID (iso-abbrev): Eur J Appl Physiol

Title: European Journal of Applied Physiology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1439-6319

ISSN (Electronic): 1439-6327

Publication date (Electronic): 16 April 2022

Publication date PMC-release: 16 April 2022

Publication date (Print): 2022

Volume: 122

Issue: 6

Pages: 1531-1541

Affiliations

[1 ]GRID grid.4425.7, ISNI 0000 0004 0368 0654, Research Institute of Sport and Exercise Science, , Liverpool John Moores University, ; Tom Reilly Building, Byrom Street, Liverpool, L3 3AF UK

[2 ]GRID grid.23695.3b, ISNI 0000 0004 0598 9700, School of Sport, , York St. John University, ; York, UK

[3 ]GRID grid.1012.2, ISNI 0000 0004 1936 7910, School of Sport Science, Exercise and Health, , The University of Western Australia, ; Perth, Australia

[4 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, , University of Liverpool, ; Liverpool, UK

[5 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Geriatric Medicine and Donders Institute for Brain, Cognition and Behaviour, , Radboud University Medical Center, ; Nijmegen, The Netherlands

[6 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Physiology, Radboud Institute of Health Sciences, , Radboud University Medical Center, ; Nijmegen, The Netherlands

Author notes

Communicated by Ellen Adele Dawson.

Author information

Helen Jones http://orcid.org/0000-0001-8282-1459

Article

Publisher ID: 4933

DOI: 10.1007/s00421-022-04933-3

PMC ID: 9132800

PubMed ID: 35429292

SO-VID: f11c3768-27ef-41c7-9185-ed57e0e92426

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 3 October 2020

Date accepted : 8 March 2022

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ScienceOpen disciplines: Anatomy & Physiology

Keywords: cerebral autoregulation,cardiac baroreflex sensitivity,cardio-respiratory fitness,ageing

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ScienceOpen disciplines: Anatomy & Physiology

Keywords: cerebral autoregulation, cardiac baroreflex sensitivity, cardio-respiratory fitness, ageing

The impact of age, sex, cardio-respiratory fitness, and cardiovascular disease risk on dynamic cerebral autoregulation and baroreflex sensitivity

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Results

Conclusion

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Most cited references 56

Stroke Risk Factors, Genetics, and Prevention.

Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies

Cerebral autoregulation dynamics in humans.

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