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.

BACKGROUND Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end stage renal disease (ESRD). In Western countries, Blacks with ESRD appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data on the association of ethnic differences in vascular calcification and survival in ESRD from Sub-Saharan Africa. METHODS This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score (lateral abdominal radiograph) and vascular stiffness by pulse wave velocity. RESULTS Sixty-six of the original 74 participants, studied a baseline, were identified. The median age was 46.6 years (37.6-59.2) and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks [baseline range 0-5, follow up range 0-8 (p=1.00)], but a nonsignificant trend to progression among non-Blacks [baseline range 0-19, follow up range 0-22 (p=0.066)]. Black participants did not display a survival advantage (p=0.870). Overall, sepsis was the most common cause of mortality (64% of those with an identifiable cause of death). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p=0.036). After adjustment for parathyroidectomy at follow up, the odds ratio of having abdominal vascular calcification score of ≥1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p= 0.03). Central aortic systolic pressures (CASP) and pulse wave velocities (PWV) were higher in the study population than age matched normative values. At follow up, a positive correlation (r=0.3) was observed between PWV and abdominal aortic calcification (p=0.04). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality. CONCLUSION There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks highlighting possible ethnic differences in calcium phosphate metabolism in patients with ESRD. The lack of vascular calcification progression in Blacks was not however associated with improved survival, but the sample size was small.

The thesis is concerned with the analysis of measuring pulse wave velocity in human body with the aid of whole-body multichannel bioimpedance which was developed at ISI AS CR, v.v.i.. The evaluation of pulse wave velocity can provide us with important information about the state of vessel compliance which is one of the basic parameters informing on their physiological state. The examination of the state of vascular system is a very important part of early diagnostics because its pathological states are the main contributor to the rise of cardiovascular diseases and disease mortality. The thesis is concerned with the theoretical analysis together with the available methods of valuation of the state of vascular system that use measuring of pulse wave velocity. The main part of the thesis deals with the analysis of the whole-body multichannel bioimpedance measurement. The proposed and programmed protocol that summarizes and visualizes all obtained information is a part of this thesis. This is currently used as an output of the experimental measurement by this method. Data file for statistical processing contains the values of the pulse wave velocity of 35 healthy volunteers and subsequently the properties of pulse wave are assessed at various excitations.

Gallstones have been linked to dyslipidemia, metabolic syndrome and cardiovascular disease. Arterial stiffness is an indicator of subclinical atherosclerosis. The aim of this study was to prospectively examine the relationship between gallstone disease and arterial stiffness progression in 347 men and 454 women. These subjects were followed for 7 years. Arterial stiffness progression was measured based on increases in brachial-ankle pulse wave velocity. Changes in brachial-ankle pulse wave velocity during the study period were significantly greater in patients with gallstones than in subjects without gallstones. After adjusting for multiple risk factors, gallstone disease was found to be a significant and independent predictor of brachial-ankle pulse wave velocity progression (β=0.189; P<0.001). In conclusion, gallstone disease is an independent predictor of arterial stiffness progression, even after adjusting for other cardiovascular risk factors.

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BACKGROUND: Electronic cigarettes (e-cigarettes) are nicotine delivery systems that generate an aerosol that can be inhaled and come in a variety of attractive designs and e- liquid flavorings. E-cigarettes are the second most commonly used tobacco product in the United States and are predominantly used by youth and young adults. The cardiovascular health risk of combustible cigarette use is well-established, but whether e-cigarettes increase the risk of cardiovascular events is less clear. Evaluating the short-term vascular effects of e-cigarette use is an approach to gain insight into the cardiovascular health impact. Limited studies have shown that acute e-cigarette use in combustible cigarette users was associated with increased central hemodynamic values and arterial stiffness. Few studies have assessed the effects of chronic e-cigarette use on arterial stiffness, particularly in young adults. OBJECTIVE: To assess the effects of e-cigarette use on central hemodynamics and arterial stiffness in regular e-cigarette users in comparison to combustible cigarette users and non-users. METHODS: Combustible cigarette users, e-cigarette users, and non-users without known cardiovascular disease (CVD) or CVD risk factors between the ages of 18 and 45 were enrolled in the ongoing Cardiovascular Injury due to Tobacco Products 2.0 (CITU 2.0) study at the Boston University School of Medicine and the University of Louisville School of Medicine starting from 2019. Non-invasive arterial tonometry, using the SphygmoCor system, was performed to measure peripheral artery waveforms to obtain central hemodynamic values and arterial stiffness parameters: augmentation index (AIx), carotid-radial (CR) and carotid-femoral pulse wave velocities (CFPWV). RESULTS: We had available arterial stiffness measures in 209 study participants (mean age 26±7, 48% female) across 3 tobacco product use groups: combustible cigarette users (N=51), e-cigarette users (N=97), and non-users (N=61). Amongst the e-cigarette users, 41 were dual users (use of both e-cigarettes and combustible cigarettes), 25 were exclusive e-cigarette users who were former combustible cigarette users, and 31 were exclusive e-cigarette users who were never combustible cigarette users. The majority (87%) of e-cigarette users used a pod-based product with fruit and mint/wintergreen or menthol as the most popular e-liquid flavors. In unadjusted analyses, central systolic blood pressure, AIx, CRPWV, and CFPWV differed across the three tobacco product use categories. In multivariable regression models adjusting for age, sex, race and study site, e-cigarette users and combustible cigarette users had higher central systolic blood pressure (β=3.9±2.0, p=0.048 and β=4.8±2.4, p=0.04, respectively) whereas combustible cigarette smokers also had higher central AIx, and CRPWV compared to non-users (β=6.9±3.3, p=0.04 and β=0.97±0.31, p=0.002, respectively). In unadjusted analyses across the five groups, we found similar patterns of differences in vascular measures. In multivariable regression models comparing to combustible cigarette users, dual product users had similar measures of vascular function whereas exclusive e-cigarette users who were former smokers had lower CRPWV (β=-0.95±0.36, p=0.009), and exclusive e- cigarette users who were never combustible cigarette users had lower AIx (β=-9.0±4.2, 0.04). CONCLUSIONS: Our findings suggest that in young adults, combustible cigarette use is associated with measures of arterial stiffness. Dual e-cigarette use was largely similar to combustible cigarette use whereas exclusive e-cigarette use had a lesser degree of vascular stiffening. Further studies are needed to evaluate the long-term impact of e- cigarette use on cardiovascular health.

The purpose of our work is to estimate arterial stiffness based on the virtual fields method and using pressure gradients and arterial wall motion. Currently, the gold standard to estimate arterial stiffness relies primarily on the pulse wave velocity, which provides a relation between arterial stiffness and the velocity of the pressure wave propagating through the arterial wall. The pulse wave velocity method has been improved over the years, but still depends on specific assumptions regarding, for example, blood pressure, arterial geometry, and linear material response. The proposed method directly links arterial wall displacements and pressure gradients to arterial stiffness and paves the way to computing arterial stiffness with higher accuracy.

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Although blood viscosity is an important component in determining vascular function, it is often assumed constant. Emerging evidence linking individual differences in viscosity to cardiovascular disease casts doubt on this assumption. The purpose of this study was to determine the contribution of whole blood viscosity to key measures of vascular function. To address this aim as comprehensively as possible, first, whole blood viscosity was compared with traditional risk factors for cardiovascular disease. Then flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cfPWV), and carotid artery compliance were calculated either with or without blood viscosity taken into account. Lastly, we tested whether the removal of blood viscosity could influence well-established associations between age and vascular function. Blood viscosity and vascular function were measured in 97 adults ranging in age from 18-63 years. No significant differences were observed between whole blood viscosity and traditional risk factors for cardiovascular disease. Whole blood viscosity was not significantly correlated with FMD, cfPWV, and carotid compliance. As expected, age was positively correlated with cfPWV (r=0.65, p<0.001) and negatively correlated with FMD (r=-0.21, p<0.05) and carotid compliance (r=-0.45, p<0.01). Even after controlling for viscosity, these relationships remained statistically significant (cfPWV r=0.65, p<0.001; FMD r=-0.24, p<0.05; carotid compliance r=-0.44, p<0.05). These results indicate that whole blood viscosity does not appear to significantly impact measures of vascular function and that the rationale for including whole blood viscosity in the calculation of vascular function remains weak. / text