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Abstract This thesis describes the laser Doppler technique based on a self-mixing effect in a diode laser to noninvasive cardiovascular pulse detection in a human wrist above the radial artery. The main applications of self-mixing interferometry described in this thesis in addition to pulse detection are arterial pulse shape and autonomic regulation measurements. The elastic properties of the arterial wall are evaluated and compared to pulse wave velocity variation at different pressure conditions inside the radial artery. The main advantages of self-mixing interferometry compared to conventional interferometers are that the measurement set up is simple, because basically only one optical component, the laser diode, is needed. The use of fewer components decreases the price of the device, thus making it inexpensive to use. Moreover, an interferometer can be implemented in a small size and it is easy to control because only one optical axis has to be adjusted. In addition, an accuracy, which corresponds to half of the wavelength of the light source, can be achieved. These benefits make this technique interesting for application to the measurement of different parameters of the cardiovascular pulse. In this thesis, measurement of three different parameters from cardiovascular pulsation in the wrist is studied. The first study considers arterial pulse shape measurement. It was found that an arterial pulse shape reconstructed from the Doppler signal correlates well to the pulse shape of a blood pressure pulse measured with a commercial photoplethysmograph. The second study considers measurement of autonomic regulation using the Doppler technique. It was found that the baroreflex part of autonomic regulation can be measured from the displacement of the arterial wall, which is affected by blood pressure variation inside the artery. In the third study, self-mixing interferometry is superimposed to evaluate the elastic properties of the arterial wall. It was found that the elastic modulus of the arterial wall increases as blood pressure increases. Correlations between measurements and theoretical values were found but deviation in measured values was large. It was noticed that the elastic modulus of the arterial wall and pulse wave velocity behave similarly as a function of blood pressure. When the arterial pressure increases, both the elastic modulus and pulse wave velocity reach higher values than in lower pressure.

Introdução: Existe crescente interesse em identificar marcadores de risco para eventos cardiovasculares em pacientes com HIV/aids. Atualmente observa-se alteração do perfil epidemiológico desses pacientes, com diminuição da mortalidade por infecção e comorbidades e aumento por eventos cardiovasculares. A elasticidade arterial, principalmente dos pequenos vasos, tem sido investigada como alteração precoce de evento cardiovascular. Objetivo: Avaliar a relação entre elasticidade arterial e outros indicadores de risco cardiovascular como fatores demográficos e socioeconômicos, hábitos de vida, estado nutricional e marcadores inflamatórios. Métodos: Foram selecionados aleatoriamente 132 indivíduos voluntários em tratamento regular com antirretrovirais em ambulatório especializado em HIV/aids, com idade entre 19 e 59 de ambos os sexos. A elasticidade arterial dos grandes vasos (LAEI) e pequenos vasos (SAEI) foi investigada pelo equipamento HDI/ PulseWaveTM CR-2000 Cardio Vascular Profiling System®. Foram determinados colesterol total e frações, triglicérides, proteína C-reativa, fibrinogênio, medidas antropométricas e de avaliação de composição corporal, fumo, consumo de bebidas alcoólicas, uso de drogas, prática de atividade física, além de avaliação de fatores demográficos e socioeconômicos e imunológicos (carga viral, T-CD4, T-CD8). Para investigar a associação entre LAEI e SAEI e outros fatores de risco cardiovascular utilizou-se análise de regressão linear múltipla. Resultados: Em relação à elasticidade dos grandes e pequenos vasos, 71,97 por cento e 32,58 por cento , respectivamente, dos participantes foram classificados com elasticidade normal. Observou-se associação positiva entre LAEI e peso (p<0,001) e associações negativas entre LAEI e prega cutânea subescapular (p<0,001) e linfócitos T-CD4 (p<0,02). Verificou-se associação negativa de LAEI com sexo (p<0,02), mostrando que o sexo feminino está relacionado com menor elasticidade. Houve associação positiva entre SAEI e peso (p<0,001) e associações negativas entre SAEI e prega cutânea subescapular (p<0,001), idade (p<0,01) e linfócitos totais (p<0.01). Conclusão: As alterações de elasticidade arterial em pacientes HIV/aids apresentaram relação com outros fatores de risco cardiovascular. SAEI mostrou-se diminuído na maioria dos participantes, sendo uma alteração que pode identificar a disfunção endotelial antes que a doença se torne clinicamente aparente. A monitoração constante da elasticidade arterial através de método não invasivo pode se tornar uma importante ferramenta na predição e prevenção de eventos cardiovasculares em pacientes HIV/aids / Introduction: There is a growing interest in identifying markers of risk for cardiovascular events in patients with HIV / AIDS. Currently there is a change in the epidemiological profile of patients with reduced mortality from infections and comorbidities and increased cardiovascular events. The arterial elasticity, mainly of small vessels, has been investigated as early alteration of cardiovascular events. Objective: To evaluate the relationship between arterial elasticity and other cardiovascular risk factors such as demographic and socioeconomic factors, lifestyle habits, nutritional status and inflammatory markers. Methods: We randomly selected 132 individuals volunteers, ages between 19 and 59, of both sexes, regularly treated with antiretrovirals in specialized clinics on HIV / AIDS. Arterial elasticity of the large (LAEI) and small (SAEI) vessels were investigated by the equipment HDI/ PulseWaveTM CR-2000 Cardio Vascular Profiling System®. We determined total cholesterol, HDL, triglycerides, C-reactive protein, fibrinogen, and anthropometric assessment of body composition, smoking, alcohol consumption, drug use, physical activity, and evaluation of demographic, socio-economic and immunological (viral load, T-CD4, T-CD8) factors. The association between LAEI and SAEI and other cardiovascular risk factors were assessed by multiple linear regression. Results: Regarding the elasticity of large and small vessels, 71.97 per cent and 32.58 per cent , respectively, of the participants were classified as having normal elasticity. We observed a positive association between LAEI and weight (p <0.001) and negative associations between LAEI and subscapular skinfold (p <0.001) and CD4 counts (p <0.02). There was a negative association of LAEI with gender (p <0.02), showing that female gender is associated with lower elasticity. There was a positive association between SAEI and weight (p <0.001) and negative associations between SAEI and subscapular skinfold (p <0.001), age (p <0.01) and total lymphocytes (p <0.01). Conclusion: Changes in arterial elasticity in patients with HIV / AIDS correlate with other cardiovascular risk factors. SAEI was altered in most participants, a change that can identify endothelial dysfunction before the disease becomes clinically apparent. The constant monitoring of arterial elasticity through noninvasive method may become an important tool in the prediction and prevention of cardiovascular events in HIV / aids patients

Introdução - Estudos mostram maior ocorrência de complicações cardiovasculares na população HIV/aids. Alguns estudos envolvendo animais e indivíduos saudáveis ou com outras doenças observaram benefícios no consumo de chocolate e erva mate na função endotelial e vasodilatação. Objetivo Avaliar o efeito da ingestão de chocolate e erva mate na elasticidade arterial de indivíduos com HIV/aids em terapia antirretroviral. Métodos Ensaio clínico cruzado, aleatorizado e duplo-cego, envolvendo 89 indivíduos com HIV/aids entre 19 e 59 anos, em tratamento regular com antirretrovirais por no mínimo 6 meses, e carga plasmática do HIV <500 cópias/ml. Os indivíduos receberam suplementação diária com aproximadamente 65g de chocolate amargo, 3g de erva mate ou respectivos placebos por 15 dias, com washout de igual tempo entre as intervenções. A aferição da elasticidade arterial foi realizada por análise do formato da onda de pulso com o equipamento HDI/PulseWaveTM CR-2000®. Também foram avaliados: composição corporal, glicemia, perfil lipídico, proteína C-reativa e concentração plasmática de espécies reativas ao ácido tiobarbitúrico (TBARS). As respostas entre tratamentos foram avaliadas por ANOVA e por teste t de Student pelo Stata® 11.0, considerando-se p< 0,005. Resultados A população foi composta principalmente por homens (62,9 por cento) caucasianos (46,1 por cento) com idade média de 44,6 ± 7,1 anos. O tempo médio de diagnóstico de HIV/aids foi de 13,2 ± 4,8 anos com 10,6 ± 5,1 anos de terapia antirretroviral. Não foram encontradas diferenças significantes na elasticidade arterial dos pequenos e grandes vasos após as suplementações. Conclusão Este é o primeiro estudo a avaliar o efeito da ingestão de erva mate e chocolate na elasticidade arterial de indivíduos com HIV/aids. Apesar das evidências positivas desses alimentos na saúde cardiovascular de animais e indivíduos com outras doenças, os mesmos efeitos não foram observados neste estudo. Provavelmente o tempo de suplementação, a biodisponibilidade das substâncias bioativas e o metabolismo alterado desses indivíduos interferiram nos resultados obtidos, sugerindo a necessidade de melhor investigação desses fatores / Introduction There has been an increase on cardiovascular diseases occurrence in the HIV/aids population. Some studies involving animals and healthy individuals or individuals with other pathologies have shown benefits on endothelial function and vasodilation under use of chocolate and yerba maté. Objective To evaluate the effect of chocolate and yerba maté intake on HIV/aids patient´s arterial elasticity. Methods Double-blind crossover trial including 89 HIV/aids patients, 19 to 59 years of age, on antiretroviral therapy for at least six months, and with viral load <500copies/ml. The individuals consumed daily approximately 65g of dark chocolate, 3g of yerba maté or placebo during 15 days, followed by a 15-day washout period after each intervention. Arterial elasticity was measured using the HDI/PulseWaveTM CR-2000 CardioVascular Profiling System®, which provides a pulse wave contour analysis. Body composition, glicemic index, lipid profile, C-reactive protein and thiobarbituric acid reactive substances (TBARS) were also assessed. The crossover analysis was performed using analysis of variance (ANOVA) on Stata®. The paired Students t-test was also applied. A p value <0.05 was considered significant. Results Most of the individuals were men (62.9 per cent), caucasian (46.1 per cent) aging 44.6 ± 7.1 years. The mean time of HIV/aids diagnosis was 13.2 ± 4.8 years, with 10.6 ± 5.1 years of antiretroviral therapy. There were no significant alterations on elasticity of either large or small arteries after chocolate and yerba maté intake. Conclusion This is the first research to evaluate the effect of chocolate and yerba maté intake on HIV/aids patient´s arterial elasticity. Despite of the positive evidence of these foods on cardiovascular health of animals and populations with other pathologies, the same effects were not observed in this study. Most probably the time of intervention, the bioavailability of the bioactive substances and the altered metabolism of this individuals interfered on the results, which indicates the need for further investigation

Introdução - Estudos mostram maior ocorrência de complicações cardiovasculares na população HIV/aids. Alguns estudos envolvendo animais e indivíduos saudáveis ou com outras doenças observaram benefícios no consumo de chocolate e erva mate na função endotelial e vasodilatação. Objetivo Avaliar o efeito da ingestão de chocolate e erva mate na elasticidade arterial de indivíduos com HIV/aids em terapia antirretroviral. Métodos Ensaio clínico cruzado, aleatorizado e duplo-cego, envolvendo 89 indivíduos com HIV/aids entre 19 e 59 anos, em tratamento regular com antirretrovirais por no mínimo 6 meses, e carga plasmática do HIV <500 cópias/ml. Os indivíduos receberam suplementação diária com aproximadamente 65g de chocolate amargo, 3g de erva mate ou respectivos placebos por 15 dias, com washout de igual tempo entre as intervenções. A aferição da elasticidade arterial foi realizada por análise do formato da onda de pulso com o equipamento HDI/PulseWaveTM CR-2000®. Também foram avaliados: composição corporal, glicemia, perfil lipídico, proteína C-reativa e concentração plasmática de espécies reativas ao ácido tiobarbitúrico (TBARS). As respostas entre tratamentos foram avaliadas por ANOVA e por teste t de Student pelo Stata® 11.0, considerando-se p< 0,005. Resultados A população foi composta principalmente por homens (62,9 por cento) caucasianos (46,1 por cento) com idade média de 44,6 ± 7,1 anos. O tempo médio de diagnóstico de HIV/aids foi de 13,2 ± 4,8 anos com 10,6 ± 5,1 anos de terapia antirretroviral. Não foram encontradas diferenças significantes na elasticidade arterial dos pequenos e grandes vasos após as suplementações. Conclusão Este é o primeiro estudo a avaliar o efeito da ingestão de erva mate e chocolate na elasticidade arterial de indivíduos com HIV/aids. Apesar das evidências positivas desses alimentos na saúde cardiovascular de animais e indivíduos com outras doenças, os mesmos efeitos não foram observados neste estudo. Provavelmente o tempo de suplementação, a biodisponibilidade das substâncias bioativas e o metabolismo alterado desses indivíduos interferiram nos resultados obtidos, sugerindo a necessidade de melhor investigação desses fatores / Introduction There has been an increase on cardiovascular diseases occurrence in the HIV/aids population. Some studies involving animals and healthy individuals or individuals with other pathologies have shown benefits on endothelial function and vasodilation under use of chocolate and yerba maté. Objective To evaluate the effect of chocolate and yerba maté intake on HIV/aids patient´s arterial elasticity. Methods Double-blind crossover trial including 89 HIV/aids patients, 19 to 59 years of age, on antiretroviral therapy for at least six months, and with viral load <500copies/ml. The individuals consumed daily approximately 65g of dark chocolate, 3g of yerba maté or placebo during 15 days, followed by a 15-day washout period after each intervention. Arterial elasticity was measured using the HDI/PulseWaveTM CR-2000 CardioVascular Profiling System®, which provides a pulse wave contour analysis. Body composition, glicemic index, lipid profile, C-reactive protein and thiobarbituric acid reactive substances (TBARS) were also assessed. The crossover analysis was performed using analysis of variance (ANOVA) on Stata®. The paired Students t-test was also applied. A p value <0.05 was considered significant. Results Most of the individuals were men (62.9 per cent), caucasian (46.1 per cent) aging 44.6 ± 7.1 years. The mean time of HIV/aids diagnosis was 13.2 ± 4.8 years, with 10.6 ± 5.1 years of antiretroviral therapy. There were no significant alterations on elasticity of either large or small arteries after chocolate and yerba maté intake. Conclusion This is the first research to evaluate the effect of chocolate and yerba maté intake on HIV/aids patient´s arterial elasticity. Despite of the positive evidence of these foods on cardiovascular health of animals and populations with other pathologies, the same effects were not observed in this study. Most probably the time of intervention, the bioavailability of the bioactive substances and the altered metabolism of this individuals interfered on the results, which indicates the need for further investigation

Introdução: Existe crescente interesse em identificar marcadores de risco para eventos cardiovasculares em pacientes com HIV/aids. Atualmente observa-se alteração do perfil epidemiológico desses pacientes, com diminuição da mortalidade por infecção e comorbidades e aumento por eventos cardiovasculares. A elasticidade arterial, principalmente dos pequenos vasos, tem sido investigada como alteração precoce de evento cardiovascular. Objetivo: Avaliar a relação entre elasticidade arterial e outros indicadores de risco cardiovascular como fatores demográficos e socioeconômicos, hábitos de vida, estado nutricional e marcadores inflamatórios. Métodos: Foram selecionados aleatoriamente 132 indivíduos voluntários em tratamento regular com antirretrovirais em ambulatório especializado em HIV/aids, com idade entre 19 e 59 de ambos os sexos. A elasticidade arterial dos grandes vasos (LAEI) e pequenos vasos (SAEI) foi investigada pelo equipamento HDI/ PulseWaveTM CR-2000 Cardio Vascular Profiling System®. Foram determinados colesterol total e frações, triglicérides, proteína C-reativa, fibrinogênio, medidas antropométricas e de avaliação de composição corporal, fumo, consumo de bebidas alcoólicas, uso de drogas, prática de atividade física, além de avaliação de fatores demográficos e socioeconômicos e imunológicos (carga viral, T-CD4, T-CD8). Para investigar a associação entre LAEI e SAEI e outros fatores de risco cardiovascular utilizou-se análise de regressão linear múltipla. Resultados: Em relação à elasticidade dos grandes e pequenos vasos, 71,97 por cento e 32,58 por cento , respectivamente, dos participantes foram classificados com elasticidade normal. Observou-se associação positiva entre LAEI e peso (p<0,001) e associações negativas entre LAEI e prega cutânea subescapular (p<0,001) e linfócitos T-CD4 (p<0,02). Verificou-se associação negativa de LAEI com sexo (p<0,02), mostrando que o sexo feminino está relacionado com menor elasticidade. Houve associação positiva entre SAEI e peso (p<0,001) e associações negativas entre SAEI e prega cutânea subescapular (p<0,001), idade (p<0,01) e linfócitos totais (p<0.01). Conclusão: As alterações de elasticidade arterial em pacientes HIV/aids apresentaram relação com outros fatores de risco cardiovascular. SAEI mostrou-se diminuído na maioria dos participantes, sendo uma alteração que pode identificar a disfunção endotelial antes que a doença se torne clinicamente aparente. A monitoração constante da elasticidade arterial através de método não invasivo pode se tornar uma importante ferramenta na predição e prevenção de eventos cardiovasculares em pacientes HIV/aids / Introduction: There is a growing interest in identifying markers of risk for cardiovascular events in patients with HIV / AIDS. Currently there is a change in the epidemiological profile of patients with reduced mortality from infections and comorbidities and increased cardiovascular events. The arterial elasticity, mainly of small vessels, has been investigated as early alteration of cardiovascular events. Objective: To evaluate the relationship between arterial elasticity and other cardiovascular risk factors such as demographic and socioeconomic factors, lifestyle habits, nutritional status and inflammatory markers. Methods: We randomly selected 132 individuals volunteers, ages between 19 and 59, of both sexes, regularly treated with antiretrovirals in specialized clinics on HIV / AIDS. Arterial elasticity of the large (LAEI) and small (SAEI) vessels were investigated by the equipment HDI/ PulseWaveTM CR-2000 Cardio Vascular Profiling System®. We determined total cholesterol, HDL, triglycerides, C-reactive protein, fibrinogen, and anthropometric assessment of body composition, smoking, alcohol consumption, drug use, physical activity, and evaluation of demographic, socio-economic and immunological (viral load, T-CD4, T-CD8) factors. The association between LAEI and SAEI and other cardiovascular risk factors were assessed by multiple linear regression. Results: Regarding the elasticity of large and small vessels, 71.97 per cent and 32.58 per cent , respectively, of the participants were classified as having normal elasticity. We observed a positive association between LAEI and weight (p <0.001) and negative associations between LAEI and subscapular skinfold (p <0.001) and CD4 counts (p <0.02). There was a negative association of LAEI with gender (p <0.02), showing that female gender is associated with lower elasticity. There was a positive association between SAEI and weight (p <0.001) and negative associations between SAEI and subscapular skinfold (p <0.001), age (p <0.01) and total lymphocytes (p <0.01). Conclusion: Changes in arterial elasticity in patients with HIV / AIDS correlate with other cardiovascular risk factors. SAEI was altered in most participants, a change that can identify endothelial dysfunction before the disease becomes clinically apparent. The constant monitoring of arterial elasticity through noninvasive method may become an important tool in the prediction and prevention of cardiovascular events in HIV / aids patients

Several research studies indicate the increasing problem obesity has become over the past few decades (Andersen 1999:41; Fox, 1999:56-60; Kuczmarshi et al., 1994:205-212). Obesity, after cigarette smoke, is the leading cause of death in the USA and a combination of diet factors and physical inactivity (two primary contributors of obesity) leads to an average of 300,000 deaths per year (McGinnis & Foege, 1993:2207-2212). Previously little information was available on the effect of obesity on the peripheral vascularization, and even less about the effect of obesity on arterial compliance (Raison et al., 1998:299-303). Research indicated a decrease in arterial compliance with an increase in body weight (Kumaran et al., 2002:7; Sutton-Tyrrell et al., 2001:431; Tounian et al., 2001:1400-1404; Stepniakowski & Egan, 1995:R567) however, contradictory research where no association between obesity and arterial compliance was indicated, has also been found (Singhal et al., 2002:1920; Mangoni et al., 1995:986). Mackey et al. (2002:16) also found that an increased aortic stiffness is positively associated with lowered physical activity levels. A lifestyle consisting of moderate physical activity, has a positive effect on the health, lowering of chronic illness risks, the prevention of cardiovascular diseases and the improvement of quality of lie in overweight and obese patients (Adams et al., 2003542; Ferreira et al., 2003:1670-1678; Macera, 2003:123; Mclnnis, 200396; Kolden et al., 2002:447). Moderate aerobic exercise is also seen as a potential non-pharmaceutical therapeutic method to increase age associated decrease in arterial compliance in young, middle aged and older adults (Gates et al., 2003:2213; Havlik et al., 2003:156; Seals, 2003:68; Moreau et al., 2003:865; Joyner, 2000:1214; Cameron et al., 1999:653). The objective of this study was firstly to determine the correlation between obesity and vascular function in Caucasian women between the ages 19 and 56 and to determine which marker of obesity is the best predictor of a weakened vascular function (see article one). The second objective was to determine the correlation between physical activity, obesity and arterial compliance in Caucasian women between the ages 19 and 56 years (see article 2). A total of 115 Caucasian women were recruited to participate in this study. Anthropometric measurements and a comprehensive body composition profile was taken using the BOD POD. The Finometer apparatus was used to measure the arterial compliance and the sphygmomanometer to measure the subjects blood pressure. The subjects completed the Yale Physical Activity Survey questionnaire to determine their physical activity index. This study seems to indicate a positive relationship between arterial compliance and obesity which could be explained by the influence blood volume had in determining arterial compliance. A negative correlation was found between obesity and blood pressure where an increase in obesity caused an increase in both systolic and diastolic blood pressure. A positive correlation was found between physical activity and obesity. The higher the activity levels were in this study, the less obese the subjects tended to be. No correlation was found between physical activity and arterial compliance. A clear trend, even though no statistically significant differences, was found between physical activity and blood pressure. The more active the subjects were, the lower their blood pressure tended to be. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2005

Several research studies indicate the increasing problem obesity has become over the past few decades (Andersen 1999:41; Fox, 1999:56-60; Kuczmarshi et al., 1994:205-212). Obesity, after cigarette smoke, is the leading cause of death in the USA and a combination of diet factors and physical inactivity (two primary contributors of obesity) leads to an average of 300,000 deaths per year (McGinnis & Foege, 1993:2207-2212). Previously little information was available on the effect of obesity on the peripheral vascularization, and even less about the effect of obesity on arterial compliance (Raison et al., 1998:299-303). Research indicated a decrease in arterial compliance with an increase in body weight (Kumaran et al., 2002:7; Sutton-Tyrrell et al., 2001:431; Tounian et al., 2001:1400-1404; Stepniakowski & Egan, 1995:R567) however, contradictory research where no association between obesity and arterial compliance was indicated, has also been found (Singhal et al., 2002:1920; Mangoni et al., 1995:986). Mackey et al. (2002:16) also found that an increased aortic stiffness is positively associated with lowered physical activity levels. A lifestyle consisting of moderate physical activity, has a positive effect on the health, lowering of chronic illness risks, the prevention of cardiovascular diseases and the improvement of quality of lie in overweight and obese patients (Adams et al., 2003542; Ferreira et al., 2003:1670-1678; Macera, 2003:123; Mclnnis, 200396; Kolden et al., 2002:447). Moderate aerobic exercise is also seen as a potential non-pharmaceutical therapeutic method to increase age associated decrease in arterial compliance in young, middle aged and older adults (Gates et al., 2003:2213; Havlik et al., 2003:156; Seals, 2003:68; Moreau et al., 2003:865; Joyner, 2000:1214; Cameron et al., 1999:653). The objective of this study was firstly to determine the correlation between obesity and vascular function in Caucasian women between the ages 19 and 56 and to determine which marker of obesity is the best predictor of a weakened vascular function (see article one). The second objective was to determine the correlation between physical activity, obesity and arterial compliance in Caucasian women between the ages 19 and 56 years (see article 2). A total of 115 Caucasian women were recruited to participate in this study. Anthropometric measurements and a comprehensive body composition profile was taken using the BOD POD. The Finometer apparatus was used to measure the arterial compliance and the sphygmomanometer to measure the subjects blood pressure. The subjects completed the Yale Physical Activity Survey questionnaire to determine their physical activity index. This study seems to indicate a positive relationship between arterial compliance and obesity which could be explained by the influence blood volume had in determining arterial compliance. A negative correlation was found between obesity and blood pressure where an increase in obesity caused an increase in both systolic and diastolic blood pressure. A positive correlation was found between physical activity and obesity. The higher the activity levels were in this study, the less obese the subjects tended to be. No correlation was found between physical activity and arterial compliance. A clear trend, even though no statistically significant differences, was found between physical activity and blood pressure. The more active the subjects were, the lower their blood pressure tended to be. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2005

Introduction – Objectives. The cardiovascular system is in direct and constant interaction with its environment. Exposure to various environmental parameters, such as low temperature, air pollution and tobacco smoke, has been strongly associated with serious or even fatal cardiovascular outcomes. Arterial stiffening and greater wave reflection are age-related vascular modifications that lead to an increased risk of cardiovascular events. The aim of this work was to explore the relationship between selected environmental factors and arterial elastic properties in an effort to elucidate the underlying mechanisms that link these factors to increased cardiovascular mortality.<p><p>Study 1: Effects of cold exposure on central and peripheral vascular tone. Our first study explored the effects of cold exposure on aortic stiffness and peripheral microvascular tone. We observed that cold exposure, in addition to its chronotropic effects, provoked an increase in aortic stiffness, as assessed by aortic pulse wave velocity, as well as significant vasoconstriction of peripheral arterioles in the microcirculation. Moreover, we explored the magnitude of this effect in a different population (Black subjects of African origin), which is traditionally characterized by exaggerated reactions to adrenergic stimuli. We noted that the vascular reactions, in terms of both aortic stiffness and microvascular vasoconstriction, were more profound in Black Africans than in age-matched Caucasian-Whites. These results argue for a direct effect of cold exposure on arterial stiffness and peripheral vascular tone, probably through activation of the orthosympathetic system.<p><p>Study 2: Exposure to ambient particulate matter and arterial stiffness. We explored the effects of acute exposure to outdoor particulate matter on aortic stiffness and aortic wave reflection. We studied the relationship between central hemodynamic parameters and ambient concentration of particulate matter in a population of patients who attended the Hypertension Clinics of Athens University. After statistical correction for a number of potential confounders, we did not observe an association between ambient concentrations of particulate matter and aortic stiffness. However, in men, particulate matter concentration was related to the amplitude of the reflected wave reaching the aorta from the periphery. These results suggest a direct acute interaction between particulate matter concentration and vascular tone, leading to an enhanced arterial wave reflection.<p><p>Study 3: The role of nicotine on the vascular effects of environmental tobacco smoke. Environmental tobacco smoke is considered as the most important source of particulate matter in the indoor environment. We recently demonstrated that exposure to tobacco smoke augmented wave reflection, an effect that was not seen after equivalent exposure to the smoke of non-tobacco, herbal cigarettes. We also noticed that the increased wave reflection was proportional to the plasma concentrations of nicotine. However, a direct causal effect between nicotine, arterial wave reflection and aortic stiffness has never been clearly demonstrated. We observed that increasing nicotine plasma concentration to levels comparable to those seen after extensive exposure to environmental tobacco smoke, provoked an increase in both aortic stiffness and arterial wave reflection after correction for heart rate and blood pressure changes. These results confirm the significant participation of nicotine in the vascular effects of passive smoking.<p><p>Conclusions. Globally, our results reveal the deleterious effects of cold, particulate matter exposure, and nicotinic stimulation on arterial stiffness, peripheral microcirculation and aortic wave reflection. The hemodynamic modifications associated with these effects may at least partially explain the causal relation between cold exposure, ambient air pollution and cardiovascular mortality.<p><p>Introduction-Objectifs. Le système cardiovasculaire est en relation directe et constante avec l’environnement. L’exposition au froid, la pollution atmosphérique et le tabagisme passif sont associés à des événements cardiovasculaires aigus graves et même fatals. La rigidification des artères et l’intensification de la réflexion de l’onde de pouls au niveau de l’aorte accompagnent le vieillissement et prédisent un risque cardiovasculaire accru. Nous avons testés l’hypothèse que les effets cardiovasculaires délétères des facteurs environnementaux comportent une altération des propriétés élastiques artérielles. Ceci pourrait être un des mécanismes physiopathologiques qui lie la mortalité cardiovasculaire aux variables environnementales.<p><p>Étude 1 :Exposition au froid ;effets centraux et périphériques. Notre première étude portait sur l’effet de l’exposition au froid sur la rigidité aortique et le tonus vasculaire des artérioles périphériques. Nous avons démontré que l’exposition au froid, hormis ses effets chronotropes, provoquait une augmentation de la rigidité artérielle – mesuré par la vitesse de l’onde de pouls au niveau de l’aorte - ainsi qu’une vasoconstriction importante au niveau des artérioles de la microcirculation. Nous avons ensuite déterminé l’amplitude de cet effet dans une autre population (sujets Africains-Noirs) qui se caractérise par des réactions plus prononcées aux différentes stimulations adrénergiques. Nous avons observé que les réactions vasculaires, tant au niveau de la rigidité aortique qu’au niveau de la microcirculation, étaient plus marquées chez les Africains-Noirs que chez les Caucasiens. Ces résultats révèlent un effet délétère de l’exposition au froid sur la rigidité aortique et le tonus vasculaire des artères périphériques, probablement via une activation du système orthosympathique.<p><p>Étude 2 :Exposition aux microparticules atmosphériques et rigidité artérielle. Nous avons ensuite investigué les effets de la pollution atmosphérique sur la rigidité artérielle et la réflexion de l’onde de pouls vers l’aorte. Nous avons étudié la relation entre les paramètres hémodynamiques centraux et la concentration atmosphérique de microparticules dans une population de patients qui ont consulté la Clinique Universitaire d’Hypertension Artérielle d’Athènes. Après correction statistique pour les facteurs confondants, nous n’avons pas observé de corrélation entre la rigidité artérielle et le taux de microparticules atmosphériques dans l’ensemble de la population investiguée. Par contre, si on restreint l’analyse aux résultats obtenus chez les sujets masculins, on s’aperçoit que la concentration atmosphérique de microparticules était associée de façon significative avec l’amplitude de l’onde réfléchie par la périphérie vers l’aorte et la pression pulsée aortique. Ces résultants suggèrent un effet direct des microparticules au niveau de la microcirculation. L’augmentation de l’amplitude de l’onde réfléchie consécutive à une vasoconstriction périphérique, modifie vraisemblablement les pressions au niveau de l’aorte chez le sujet masculin lors de pics de pollution.<p><p>Etude 3 :Le rôle de la nicotine dans les effets vasculaires du tabagisme passif. Le tabagisme passif est considéré comme la source la plus importante d’émission de microparticules au niveau domestique. Cependant, la composition chimique des particules semble jouer un rôle essentiel sur les ondes de réflexion. Nous avons démontré récemment que l’exposition passive à la fumée des cigarettes du tabac augmente l’intensité de la réflexion de l’onde de pouls. Ceci n’a pas été observé avec l’exposition à la fumée des cigarettes non tabagiques, en dépit d’une concentration ambiante tout à fait comparable de microparticules. Par ailleurs, nous avons observé que l’augmentation de l’incidence de l’onde de pouls au niveau de l’aorte était fortement associée à la concentration plasmatique de la nicotine. Un lien causal entre la nicotine, réflexion de l’onde de pouls et rigidité artérielle n’avait jamais clairement été établi. Nous avons testé cette hypothèse en administrant la nicotine pure chez des sujets sains. Nous avons observé que l’augmentation des taux plasmatiques de la nicotine à des valeurs comparables à celles qui surviennent après une exposition intensive au tabagisme passif, intensifiait la réflexion de l’onde de pouls et augmentait la rigidité artérielle. La correction statistique pour l’augmentation de la fréquence cardiaque et l’augmentation de la pression artérielle en réponse à la nicotine ne modifiait pas ces conclusions. Nos résultats démontrent ainsi les effets cardiovasculaires importants de faibles concentrations de nicotine, similaires à ceux qui sont atteints en cas d’exposition à un tabagisme passif.<p><p>Conclusions. Nos résultats révèlent les effets néfastes de l’exposition au froid et aux microparticules atmosphériques sur la rigidité artérielle, la microcirculation périphérique et la réflexion de l’onde de pouls. Nous avons pu également démontrer le rôle de la stimulation nicotinique dans les effets vasculaires aigus du tabagisme passif, comme en témoigne l’augmentation de la réflexion de l’onde de pouls au niveau aortique. Ces modifications hémodynamiques favorisent l’ischémie myocardique, et constituent un des mécanismes par lesquels l’exposition au froid et à la pollution atmosphérique favorisent la pathologie cardiovasculaire.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished