The role of physical activity, cardiorespiratory fitness and exercise on the autonomic and arterial systems of healthy adolescents

Cardiovascular diseases (CVD) are the leading cause of death worldwide and the atherosclerotic process that precedes CVD starts during childhood. Physical activity (PA), cardiorespiratory fitness (CRF) and exercise are well known as preventive strategies for CVD. One possible mechanism for such prevention is the role of PA, CRF and exercise on the arterial and autonomic systems. The aim of this thesis was to investigate using observational and experimental studies the role of PA, CRF and exercise on the autonomic and arterial systems of healthy adolescents. Chapter 4 systematically reviewed observational cross-sectional studies and provided level one evidence for a significant and positive association between resting parasympathetic function and moderate-to-vigorous PA in youth. Chapter 4 also indicated that gaps exist in the literature such as the associations between PA intensities, CRF and heart rate variability (HRV). These findings were furthered in Chapter 5 which showed that vigorous PA (VPA) and moderate PA (MPA) were positively related with HRV at rest and cardiac autonomic recovery following exercise in adolescents. In Chapter 6 a high-fat meal was used aiming to increase CVD risk in the postprandial state, and it was demonstrated that PA levels and CRF are not significantly associated with postprandial HRV and arterial stiffness in adolescents. Aiming to investigate possible associations between the vascular and autonomic system, measures of baroreflex sensitivity (BRS) were introduced. Chapter 7 showed that BRS and its autonomic and vascular components present a between-day coefficient of variation lower than 20% whilst within day coefficient of variations were lower than 34% in adolescents. In Chapter 8 acutely following high- and moderate-intensity interval exercise a decrease in blood pressure was observed concomitantly with decreases in BRS. This was mainly mediated by decreases in the autonomic modulation, and the duration of the decreases in blood pressure was higher following high-intensity interval exercise. Chapter 9 extended these findings by demonstrating that the changes in BRS following the ingestion of glucose was not altered by the high or moderate-intensity exercise performed before glucose ingestion. Chapter 10 showed that following four weeks of high-intensity exercise interval training no improvements were observed in BRS and its autonomic and vascular components at rest or acutely following exercise. Collectively, the present thesis contributes significantly to the literature by providing novel evidence in healthy adolescents on the role of PA intensities, CRF and exercise on the arterial and autonomic systems at rest, acutely following exercise and in the postprandial state. The results gathered in this thesis indicate potential of the autonomic and vascular function as targets of CVD risk reduction in youth.Coordenação de aperfeiçoamento de pessoal de nível superior - CAPES. Brazi

The use of subclinical vascular markers of atherosclerosis in youth

The foundations for cardiovascular disease (CVD) in adults are laid in childhood and accelerated by the presence of comorbid conditions. Early detection of manifestations of cardiovascular pathology is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Children were once considered to be at low risk, but with the growing health concerns related to lifestyle, cardiovascular screening may be needed earlier. Several noninvasive procedures are available to assess the cumulative effect of these exposures. These include carotid ultrasound, flow-mediated dilation, pulse wave velocity and measures left ventricular mass. This dissertation analyzes the comorbid conditions that increase cardiovascular risk in youth, namely obesity and low physical fitness, using carotid intima-media thickness to objectively detect early manifestations of cardiovascular pathology. Until recently researchers have not used surrogate markers of subclinical atherosclerosis to examine the role of a single bout of exercise. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables and permits greater experimental control of confounding variables. It is possible that the effects of a bout of exercise can predict the effects of chronic exercise. We analyze the physiological factors pertinent to arterial stiffness using arterial distensibility and pulse wave velocity in the context of acute exercise in children and adults. In some instances, those who amend their trajectory by not maintaining risk factors into adulthood experience reductions in subclinical markers to levels associated with never having had the risk factor. Though avoidance of risk factors in youth is ideal, there is still a window for intervention where long-lasting cardiovascular effects might be avoided. In this dissertation we present preliminary findings linking modifiable youth risk factors to subclinical markers of CVD in adulthood.As bases da doença cardiovascular (DCV) em adultos são estabelecidas na infância e aceleradas pela presença de comorbidades. A deteção precoce de manifestações da patologia cardiovascular é um objetivo clínico importante na identificação daqueles com risco de subsequente morbidade e eventos cardiovasculares, e no estabelecimento de intervenções comportamentais e médicas para reduzir o risco. As crianças já foram considerados de baixo risco, mas com as crescentes preocupações de saúde associadas ao estilo de vida, o rastreio cardiovascular é cada vez mais precoce. Vários procedimentos não invasivos estão disponíveis para avaliar o efeito cumulativo dessas exposições. Estes incluem ultrassom da artéria carótida, a dilatação fluxo-mediada, velocidade de onda de pulso e medidas da massa ventricular esquerda. Esta dissertação analisa comorbidades conhecidas que aumentam o risco cardiovascular em crianças e adolescentes, como a obesidade, pressão arterial elevada e baixa aptidão física, usando a espessura da parede intima-media da carótida para detetar objetivamente as manifestações precoces de patologia cardiovascular. Até recentemente, estes marcadores subclínicos de aterosclerose foram pouco utilizados para examinar os efeitos de uma única sessão de exercício físico. No entanto, a utilização do modelo de exercício agudo pode ser vantajoso, pois permite uma manipulação eficiente das variáveis do exercício e permite maior controle experimental de variáveis de enviezamento. É possível que os efeitos de uma sessão de exercício possam prever os efeitos do exercício crónico. Nesta dissertação analisamos os fatores fisiológicos associados à rigidez arterial usando a distensibilidade arterial e velocidade da onda de pulso no contexto de exercício agudo em crianças e adultos. Em alguns casos, aqueles que melhoram o seu perfil de risco de risco para as DCV até à idade adulta experienciam reduções em marcadores subclínicos de aterosclerose para níveis saudáveis. Embora a prevenção de fatores de risco na juventude seja o ideal, existe ainda uma janela para a intervenção em que os efeitos cardiovasculares de longa duração pode ser evitada. Nesta dissertação apresentamos resultados preliminares que ligam fatores de risco modificáveis na juventude com marcadores subclínicos de DCV na idade adulta

Cardiovascular Disease Risk in Young Adults Following Covid-19

Introduction: SARS-CoV-2, the virus responsible for COVID-19, may cause a dysregulated systemic inflammatory response that could lead to cardiovascular damage and cause individuals recovering from COVID-19 to be at an increased risk for future cardiovascular disease (CVD). Physical activity (PA) is inversely associated with systemic inflammation and CVD risk, which may make it a useful cardioprotective lifestyle factor for individuals recovering from COVID-19. Purpose: 1) Compare arterial stiffness and systemic inflammatory levels between individuals recovering from COVID-19 and uninfected controls, 2) explore systemic inflammation as a predictor of arterial stiffness, and 3) explore PA as a mediator for the relationship for COVID-19 history with arterial stiffness and systemic inflammation. Methods: Cross-sectional analysis was performed on 23 SARS-CoV-2 participants (8M/15F, 25.0±8.9 years, 24.1±3.5 kg/m2) and 32 uninfected controls (14M/18F, 24.4±6.5 years, 25.1±3.5 kg/m2). Arterial stiffness, as a proxy for CVD risk, was estimated as pulse wave velocity (PWV) during 24-hour ambulatory blood pressure monitoring using an oscillometric blood pressure device. Systemic inflammation was assessed as salivary cytokine and C-reactive protein (CRP) levels collected using the passive drool method. PA was objectively measured via accelerometry and assessed as moderate-to-vigorous physical activity (MVPA). An independent samples t-test was used to compare measures of arterial stiffness and systemic inflammation between the SARS-CoV-2 and control groups. Simultaneous multiple regression was used to assess how well proinflammatory cytokine and CRP levels predicted arterial stiffness. Mediational analysis was used to determine whether there is a significant indirect effect of COVID-19 history through MVPA on arterial stiffness and CRP levels. Results: Participants recovering from COVID-19 were studied, on average, 111.6±118.3 days after testing positive, experienced 5.2±3.8 symptoms, and had mild COVID-19 disease severity. The results from independent samples t-test showed no significant differences (all p\u3e0.05) between the SARS-CoV-2 and control group in PWV (5.0±0.5 m/s vs 5.1±0.5 m/s) , IL-8 (821.1±772.6 pg/mL vs 843.8±958.4 pg/mL), IL-1β (126.3±102.2 pg/mL vs 143.6±157.9 pg/mL), IL-6 (11.7±25.4 pg/mL vs 5.9±7.9 pg/mL), TNF-α (4.8±3.9 pg/mL vs 5.1±5.9 pg/mL), or CRP (765.4±672.9 pg/mL vs 526.3±674.8 pg/mL). Additionally, the combination of IL-8, IL-1β, IL-6, TNF-α, and CRP were not found to significantly predict PWV, with no individual measure of systemic inflammation significantly contributing to the regression equation (all p\u3e0.05). Finally, mediational analysis did not find a significant indirect effect of COVID-19 history through MVPA on PWV (estimate = 0.0220, 95% CI = -0.0488 – 0.2427) or of COVID-19 history through MVPA on CRP levels (estimate = 0.0254, 95% CI = -0.0675 – 0.1646). Conclusion: This investigation found no differences in arterial stiffness and systemic inflammation between young adults recovering from COVID-19 and uninfected controls. Additionally, systemic inflammation was not found to be a significant predictor of arterial stiffness. Finally, MVPA was not found to significantly mediate the relationship for COVID-19 history with arterial stiffness and systemic inflammation

Brain Tumour Classification Using Deep Features from Structural MRI

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Physical activity, physical function and arterial stiffness of people undergoing maintenance haemodialysis for stage 5 chronic kidney disease

This thesis addresses current issues regarding assessment of physical activity (PA) and physical function (PF) status of haemodialysis (HD) patients, specifically: What is the recommended wear time to provide a reliable accelerometer estimate of habitual PA and sedentary behaviour? Can similar outcomes from different accelerometers be used interchangeably? Do subjectively and objectively estimated PA outcomes agree closely enough to be pooled? Which PF assessments are potentially most ‘useful’? This thesis also explores potential risk factors of arterial stiffness, a strong predictor of mortality in this population. A PA reliability study involving 70 maintenance HD patients (55.9 ± 15.7 years) over a seven-day monitoring period indicated one dialysis day and two non-diaysis days with a minimum of eight hours wear per day would provide reliable estimates of PA and sedentary behaviour regardless of accelerometer employed, and allowed 90% sample retention. Concordance studies indicated broad agreement for similar outcomes obtained via ActivPAL and Actigraph GT3X accelerometers but they were not interchangeable. ActivPAL is recommended for monitoring steps taken and time seated, Actigraph activity count output for total/overall PA. Questionnaire and accelerometer estimated PA outcomes may not be used interchangeably or pooled. More of the shared variance of physical performance was explained by clinical, demographic and habitual PA factors than for self-reported functional status thus recommending the former. Age, blood pressure and HD vintage were determinants of arterial stiffness, however PA and cardiorespiratory fitness did not appear to be risk factors in this sample. This thesis makes clear recommendations regarding implementation of PA and PF assessment methods, and illustrates their application on sample retention, as well as characterising and potentially identifying individuals at risk of poor outcomes. Emergence of HD vintage as a risk factor for arterial stiffness underscores the need for further research into adjunctive lifestyle interventions to manage health threats in this population.sub_phyunpub2080_ethesesunpu

Methods and Instrumentation for Non-Invasive Assessment of the Cardiovascular Condition

Tese de doutoramento em Física (Pré-Bolonha), Especialidade de Física Tecnológica, apresentada à Faculdade de Ciências e Tecnologia da Universidade de CoimbraAs doenças cardiovasculares (DCVs) são a principal causa de morte a nível mundial e largamente responsáveis pelos custos crescentes nos sistemas de saúde. Nos últimos anos, a comunidade médica tem vindo a demonstrar um grande interesse na avaliação da rigidez arterial local, pressão arterial central e na análise da onda de pressão, devido aos seus valores preditivos no desenvolvimento deste tipo de patologias. Apesar da sua relevância, estes parâmetros hemodinâmicos permanecem particularmente difíceis de medir na prática clínica, já que a maioria dos dispositivos disponíveis exigem elevados conhecimentos técnicos (introduzindo a dependência de um operador), tecnologias dispendiosas ou apresentam abordagens de análise ineficientes. Este trabalho de investigação encontra assim a sua motivação no potencial impacto que instrumentação não-invasiva, exata e de fácil utilização pode ter na monitorização da condição hemodinâmica e no diagnóstico precoce e acompanhamento de DCVs. Neste contexto, uma nova geração de protótipos baseados na combinação de diferentes tipos de sensores eletromecânicos, bem como um conjunto de algoritmos de processamento de sinal adequados à extração de múltiplos parâmetros hemodinâmicos foram desenvolvidos. Dependendo do marcador de risco cardiovascular a ser avaliado, dois grandes grupos de dispositivos foram projetados. O primeiro grupo, focado na avaliação da rigidez arterial local, explorou uma configuração dupla inovadora com dois sensores acústicos ou piezoelétricos (PZs) para a medição da velocidade da onda de pulso (VOP) e outros índices temporais relevantes, num curto segmento da artéria carótida. O outro grupo, centrado na avaliação contínua da pressão arterial sanguínea (PAS) e onda de pressão arterial (OPA), também na artéria carótida, usou uma unidade vibrador-acelerómetro montada num mesmo suporte que permitiu ao acelerómetro detetar as vibrações produzidas, atenuadas e moduladas em amplitude quando em contacto mecânico com a parede do vaso. Os protótipos desenvolvidos foram extensivamente caracterizados em sistemas de bancada de teste, desenvolvidos para este efeito e capazes de reproduzir a variabilidade de uma ampla gama de situações clinicamente relevantes, bem como em condições in vivo. Relativamente à avaliação da rigidez arterial local, a primeira e segunda gerações de protótipos desenvolvidos apresentaram boa exatidão nos ensaios de resolução temporal realizados em tubos elásticos de bancadas de teste. O algoritmo de correlação cruzada exibiu a capacidade de medir VOPs altas (≈ 19 ms-1 e 14 ms-1) com erros relativos e coeficientes de variação inferiores a 10 % para os diferentes protótipos. Os sinais adquiridos provaram ser robustos e repetíveis, não sofrendo efeitos de crosstalk. Os resultados obtidos no estudo de validação pré-clínica em vinte indivíduos saudáveis com a segunda geração de protótipos foram ainda bastante satisfatórios. As VOPs carotídeas médias obtidas apresentaram uma correlação linear e forte entre si, estando os resultados próximos dos valores obtidos noutros estudos de referência. Além disso, a capacidade de reproduzir perfis de onda pressão distintos usando as sondas PZs foi também mostrada, quer utilizando o processo de desconvolução quer um circuito eletrónico integrador dedicado. No que diz respeito à avaliação da PAS e OPA, o processo de desmodulação produziu excelentes resultados na recuperação da morfologia da onda de pressão em condições de bancada de teste e in vivo. Para os dois protótipos desenvolvidos, várias formas de onda foram extraídas, com exatidão, das portadoras moduladas de aceleração, corrente ou potência elétricas, usando os algoritmos de deteção do envelope e do produto. Na bancada de teste foi possível reproduzir a forma de onda de pressão para posições de aplanação do tubo elástico sucessivamente mais elevadas com um erro quadrático médio de 2.4 ± 0.51 %, quando considerado o melhor método de extração. A eficácia de um novo método de calibração focado na utilização de curvas empíricas que convertem aceleração em pressão foi também demonstrado. Através da conservação da amplitude da portadora de aceleração, foi possível determinar os valores de pressão máximo, mínimo, médio e de pulso com erros relativos inferiores a 10 % em condições de bancada. Além disso, as diferenças de pressão entre o último protótipo desenvolvido e o sistema de referência foram, em média, ≤ 5 ± 8 mmHg, satisfazendo os critérios de exatidão de sistemas de medição de PAS clinicamente validados. Embora estudos de validação clínica sejam ainda necessários, os resultados globais obtidos neste trabalho para os dois principais tipos de protótipos dão bons indicadores quanto à sua utilização como alternativas válidas aos sistemas atualmente disponíveis, tanto em ambientes clínico quanto de investigação.Cardiovascular diseases (CVDs) are the leading cause of death worldwide and largely responsible for the ever increasing costs in healthcare systems. In the last few years, the medical community has demonstrated a great interest in local arterial stiffness, central blood pressure assessment and pressure waveform analysis, due to their predictive values in the development of this type of pathologies. Despite their significance, these hemodynamic parameters remain particularly challenging to measure in standard clinical practice since most available devices require high technical expertise (introducing operator dependence), burdensome technologies and/or present ineffective analysis approaches. This research work finds its motivation in the potential impact that non-invasive, accurate and easy-to-use instrumentation could have on the monitoring of hemodynamic condition and on the diagnosis and control of early stages of CVDs. In this context, a new generation of prototypes based on the combination of different types of electromechanical sensors, along with a set of signal processing algorithms suited to the extraction of multiple hemodynamic parameters were developed. Two major groups of devices were designed depending on the cardiovascular risk marker to be assessed. The first group, focused on local arterial stiffness evaluation, explored an innovative double headed probe configuration of acoustic or piezoelectric (PZ) sensors for the measurement of pulse wave velocity (PWV) and other relevant time-based indices, in a short segment of the carotid artery. The other main group, centered on the continuous assessment of arterial blood pressure (ABP) and arterial pressure waveform (APW), also at the carotid artery, used a vibrator-accelerometer unit mounted in a common support that enabled the accelerometer to sense the produced vibrations, attenuated and modulated in amplitude when in mechanical contact with the vessel wall. The developed prototypes were extensively characterized in test bench systems, purposely built and capable of reproducing the variability of a wide range of clinically relevant situations, as well as in in vivo conditions. Regarding local arterial stiffness evaluation, the first and second generations of developed prototypes presented good accuracy in time resolution experiments on elastic tubes at the test bench. Cross-correlation algorithm exhibited the capability of measuring high PWVs (≈ 19 ms-1 and 14 ms-1) with relative errors and coefficients of variation lower than 10 % for the different prototypes. The acquired signals proved to be robust and repeatable, not suffering from crosstalk effect. The results obtained in a pre-clinical validation trial of twenty healthy subjects with the second generation of prototypes were very satisfactory, demonstrating that the mean carotid PWVs obtained were linearly and strongly correlated and were in agreement with other reference studies. Additionally, the ability to reproduce distinct wave pressure profiles using the PZs probes was also shown, either using the demodulation algorithm-based process or a special circuit for electronic integration. Concerning APW and ABP assessment, the demodulation process yielded excellent results in recovering the morphology of pressure wave in test bench and in in vivo conditions. For the two developed prototypes, several waveforms were accurately extracted from the acceleration, current or power modulated carriers using the envelope and product detector algorithms. It was possible to reproduce the pressure waveform for successive higher applanation positions of the elastic tube at the test bench with a root mean square error of 2.4 ± 0.51 %, when considering the best extracting method. The effectiveness of a novel calibration method focused on the use of empirical curves which convert acceleration into pressure was also demonstrated. Through the conservation of the acceleration carrier amplitude, it was possible to determine the maximum, minimum, mean and pulse pressure values with relative errors lower than 10 % in bench conditions. Also, the mean pressure differences between the latest prototype and the reference system were, on average, ≤ 5 ± 8 mmHg, satisfying the accuracy criteria of clinically validated ABP devices. Although clinical validation studies are still required, the global results obtained in this work for the two major types of prototypes provide great prospects regarding their use as valid alternatives to currently available systems, both in clinical and research settings

The effect of sedentary behaviour on cardiovascular biomarkers in active, healthy adults

Sedentary behaviour (SB) is an independent predictor of cardiovascular disease (CVD) morbidity and mortality, yet little is known about the effect of SB on markers of cardiovascular health in active adults. Therefore the aim of the study was to determine whether increased SB is associated with greater cardiovascular risk in an active population. Twenty-six healthy participants (aged 27.9±8 years, 16 males) were recruited and visited the laboratory on two occasions. During visit one, body composition (waist and hip circumference and body fat percentage (BF%)) were measured, and following 15 minutes of supine rest, ultrasound assessment of brachial and femoral artery flow-mediated dilation (FMD) and carotid artery intima-media thickness was conducted. Carotid-femoral pulse wave velocity and middle cerebral artery blood flow velocity were assessed via applanation tonometry and transcranial Doppler ultrasonography respectively. Continuous blood pressure and carotid artery reactivity (via ultrasound) were recorded during the cold pressor test (CPT). During visit two, cardiorespiratory fitness (CRF; VO2peak) was assessed using the modified Bruce protocol. Physical activity (PA) and SB was objectively measured for seven days via accelerometry and inclinometry respectively. Participants were grouped into tertiles according to sedentary time: LoSIT (n=9), MidSIT (n=9) and HiSIT (n=8) and univariate ANCOVAs determined the effect of SB on cardiovascular biomarkers across the groups. Data is presented as mean±standard deviation. There was a significant difference between groups in hip circumference (LoSIT 96.9±3.2cm, MidSIT 99.3±4.8cm, HiSIT 106.3±7.9cm; P=0.026), BF% (LoSIT 17.81±5.80%, MiSIT 22.40±9.61%, HiSIT 27.60±7.11%; P=0.035) and VO2peak (LoSIT 50.58±3.65ml/min/kg, MidSIT 47.52±9.1465ml/min/kg, HiSIT 39.75±7.5965ml/min/kg; P=0.043). There was no effect of SB on vascular markers and CPT responsiveness (P>0.05). In conclusion, in an active population, SB appears to be detrimentally associated with CRF and body composition, whilst exceeding the guidelines of 150 minutes of moderate-vigorous or 75 minutes of vigorous intensity PA per week appears to be protective of the vasculature