Background Anthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years. Methods Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old. Results There were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV. Conclusions We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes. / <p>Funding Agencies|Medical Research Council of Southeast Sweden||Center for Medical Image Science and Visualization (CMIV)||Linkoping University||Futurum||King Gustaf V and Queen Victoria Freemason Foundation||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council Grant|12661|</p>

An age-related decline in cerebral blood flow (CBF) is widely acknowledged. However, uncertainty exists as to whether this reduction is the result of a reduced metabolic demand (cerebral atrophy) or an impaired delivery system (cerebrovascular disease). The purpose of these experiments was to examine the relationship of CBF and dynamic cerebrovascular regulation with changes in common carotid intima-media thickness (cIMT), brachial-ankle pulse wave velocity (baPWV) and common carotid distensibility. Additionally, we took an exploratory view into the effect of vascular aging and CBF reduction on brain function, as expressed through the performance of motor and cognitive tasks. An important finding in elderly participants was that seated anterior CBF declined as a function of arterial stiffness, independently of age. Linear regression analysis developed a model that predicts CBF drops 22 ml/min (95% confidence interval (CI): 6, 38) for each 100 cm/s increase in baPWV and 8 ml/min (95% CI: 1, 15) for each additional year in age. The effect of baPWV appears to be mediated through an increase in cerebrovascular resistance (r2 = 0.84, p < 0.0001). Additionally, CBF showed postural dependency and the volume of the drop in CBF between supine and seated positions was greatest in elderly participants (YOUNG: 65 ± 81 ml/min; ELDERLY: 155 ± 119 ml/min; p = 0.001). Despite this negative impact of vascular aging on steady state flow, dynamic regulation does not appear to be affected. Cerebrovascular responses to an acute drop in blood pressure or to activation of the motor cortex were not attenuated in the elderly participants. Finally, seated CBF had modest directionally relevant relationships with perceptuo-motor and complex sequencing processes; while cIMT appeared to influence performance on initiation and inhibition tasks.

An age-related decline in cerebral blood flow (CBF) is widely acknowledged. However, uncertainty exists as to whether this reduction is the result of a reduced metabolic demand (cerebral atrophy) or an impaired delivery system (cerebrovascular disease). The purpose of these experiments was to examine the relationship of CBF and dynamic cerebrovascular regulation with changes in common carotid intima-media thickness (cIMT), brachial-ankle pulse wave velocity (baPWV) and common carotid distensibility. Additionally, we took an exploratory view into the effect of vascular aging and CBF reduction on brain function, as expressed through the performance of motor and cognitive tasks. An important finding in elderly participants was that seated anterior CBF declined as a function of arterial stiffness, independently of age. Linear regression analysis developed a model that predicts CBF drops 22 ml/min (95% confidence interval (CI): 6, 38) for each 100 cm/s increase in baPWV and 8 ml/min (95% CI: 1, 15) for each additional year in age. The effect of baPWV appears to be mediated through an increase in cerebrovascular resistance (r2 = 0.84, p < 0.0001). Additionally, CBF showed postural dependency and the volume of the drop in CBF between supine and seated positions was greatest in elderly participants (YOUNG: 65 ± 81 ml/min; ELDERLY: 155 ± 119 ml/min; p = 0.001). Despite this negative impact of vascular aging on steady state flow, dynamic regulation does not appear to be affected. Cerebrovascular responses to an acute drop in blood pressure or to activation of the motor cortex were not attenuated in the elderly participants. Finally, seated CBF had modest directionally relevant relationships with perceptuo-motor and complex sequencing processes; while cIMT appeared to influence performance on initiation and inhibition tasks.

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Paraoxonase (PON) 1 is a high density lipoprotein (HDL) - bound antioxidant enzyme that was originally discovered and better known for its role in protecting against organophosphate (OP) - induced neurotoxicity. In the past two decades, the enzyme has gained prominence as a protective agent against atherosclerosis on account of increasing evidence that it accounts for many of the anti-atherogenic roles attributed to HDL. PON1 is a polymorphic enzyme displaying a high variability in human populations which is associated with a considerable degree of inter-individual differences in enzyme phenotype that translates to differential risk for OP toxicity and cardiovascular disease (CVD). In a series of studies and analyses, this thesis describes investigations regarding the possible involvement of PON 1 in the risk for CVD in a mixed ancestry population from Bellville, Western Cape, South Africa. This was done by evaluating the distribution of PON1 coding region polymorphisms (Q192R and L55M) and their influence on PON1 phenotype as well as the latter‟s relation to CVD risk factors (oxidative stress, inflammation and atherogenic dyslipidemia) and possible involvement in early CVD assessed by measuring intima media thickness of the carotid artery (CIMT). Since PON1 is increasingly measured in samples that have been stored for varied periods of time, the main study was preceded by a pilot study evaluating the influence of baseline conditions on the stability of PON 1 activity and antioxidant status in human sera stored for up to 12 months. It was shown that baseline glycemic status enhances the degradation of antioxidants in stored samples with indications of also accelerating the decline of PON1 levels and activity. Thus baseline glycemic status should be a factor to be considered in analyses involving stored samples. The Q192R polymorphism was found to be the functional variant influencing both concentration and activity of plasma PON1. Contrary to expectation, the L55M was nonfunctional, possibly due to its unusual distribution in this population where the 55M (83%) allele overwhelmingly predominated over the L55 allele. The R allele was the more frequent (60.4%) of the 192 polymorphism. The R allele has previously been associated with less efficient breakdown of lipid peroxides and a subsequent higher risk for atherosclerotic heart disease while the 55M is recognized as a “low concentration/activity” variant. Thus the predominant PON1 genotype distribution in this population constitutes a risk profile that may relate to increased risk for CVD. The risk for CVD was confirmed to be very high in this population indicated by high prevalence of the metabolic syndrome (48%) and its key components (and CVD risk factors) diabetes (28%), obesity (53%) and high blood pressure (57%). Paraoxonase activity associated inversely with indices of inflammation (high sensitive C- reactive protein [hs-CRP] and leptin) and oxidative stress (oxidized low density lipoprotein [LDL]) and directly with adiponectin and markers of systemic antioxidant status. These findings suggest that low paraoxonase-I activity contributes to increased cardiovascular risk possibly via involvement in early atherogenesis. However, only a modest inverse relation was observed between PON1 phenotype and CIMT thus suggesting that PON1 may not play a major role in early atherosclerosis. Taken together, the findings presented in this thesis demonstrate the presence of a risk PON1 genotypic profile and indication that the enzyme may play a role in the enhanced CVD risk in this population possibly via interactions with inflammation and oxidative stress. However, conclusive evidence for the involvement of PON1 in early CVD was not demonstrated indicating a need to explore the participation of PON1 in later stages of CVD. / AFRIKAANSE OPSOMMING: Paraoksonase (PON) 1 is 'n antioksidant ensiem wat aan HDL gebind is. Oorspronklik is dit ontdek en het bekend geword as 'n beskermer teen organofosfaat (OF)-gedrewe neurotoksisiteit. In die afgelope twee dekades het die ensiem belangrik geraak as 'n beskermer teen arterosklerose as gevolg van toenemende bewyse dat dit 'n belangrike rol speel in die beskermende effekte van HDL teen arterosklerose. PON1 is 'n polimorfiese ensiem wat groot variasie toon in verskillende populasies. Daar is ook inter-individuele verskille in ensiem fenotipe wat uitloop op 'n differensiele risiko vir OF toksisiteit en kardiovaskulêre hartsiekte (KVH). Hierdie tesis beskryf 'n reeks analises en ondersoeke betreffende die moontlike betrokkenheid van PON1 in die risiko vir KVH in 'n gemengdeafkoms populasie van Bellville, Wes-Kaap, Suid Afrika. Dit was gedoen deur die evaluering van die verspreiding van die PON-1 koderende omgewing polimorfismes (Q192R en L55M), hulle invloed op PON1 fenotipe en laasgenoemde se verhouding tot KVH risikofaktore (oksidatiewe stress, inflammasie en arterogeniese dislipedimie) en moontlike voorkoms in vroeë kardiovaskulêre siekte bepaal deur die meting van die intima media dikte van die karotied slagaar. Aangesien PON1 al hoe meer gemeet word in monsters wat vir verskeie tydperke gestoor word, was die hoofstudie voorafgegaan deur 'n loodsstudie wat die invloed van basislyn kondisies op die stabiliteit van PON1 aktiwiteit en antioksidant status in menslike sera wat vir tot 12 maande gestoor was, bepaal het. Dis is duidelik aangetoon dat basislyn glisemiese status die afbraak van antioksidante in gestoorde monsters verhoog het, asook aanduidings van die afname van PON1 vlakke en aktiwitetit. Basislyn glisemiese status behoort dus ook as 'n faktor ingereken te word in analises van gestoorde monsters. Die Q192R polimorfisme is aangetoon om 'n funksionele variant te wees wat beide die konsentrasie asook die aktiwiteit van PON1 beïnvloed het. Anders as wat verwag is, was die L55M polimorfisme nie-funksioneel, moontlik as gevolg van sy ongewone distribusie in hiedie populasie waar die voorkoms van die 55M (83%) alleel die L55 alleel oorheers het. Die R alleel was die mees algemene (60.4%) van die 192 polimorfisme. Die R alleel is voorheen reeds geassosieer met minder effektiewe afbraak van lipied peroksides en gevolglike hoër voorkoms van arteriosklerotiese hartsiekte, terwyl die 55M erken word as 'n “lae konsentrasie/aktiwiteit” variant. Die oorheersende PON1 genotipe distribusie in hierdie populasie behels dus 'n risikoprofiel wat betrekkking mag hê op verhoogde KVH. Die risiko vir KVH was bevestig om baie hoog te wees in hierdie populasie, soos aangedui deur 'n hoë voorkoms van die metaboliese sindroom (48%) en die sleutelkomponente daarvan (insluitend KVH risikofaktore), diabetes (28%), obesiteit (53%) en hipertensie (57%). Paraoksinase aktiwiteit was omgekeerd geassosieer met indekse van inflammasie (hoë C-reaktiewe proteïen [hs-CRP] en leptien) en oksidatiewe stres (geoksideerde lae digtheid lipoproteïen [LDL], en direk geassosieer met adiponektien en merkers van sistemiese antioksidantstatus. Hierdie bevindings mag aandui dat lae paraoksonase-1 aktiwiteit bydra tot verhoogde kardiovaskulêre risiko, moontlik via betrokkenheid in vroeë arterogenese. Slegs 'n klein omgekeerde verhouding is egter waargeneem tussen die PON1 fenotipe en karotied intima media dikte, wat mag aandui dat PON1 nie 'n beduidende rol speel in vroeë arterosklerose nie. In geheel, die bevindinge voorgedra in hierdie tesis demonstreer die voorkoms van 'n risiko PON1 genotipiese profiel wat 'n aanduiding mag wees dat die ensiem 'n rol mag speel in die verhoogde KVH risiko in hierdie populasie, moontlik deur interaksies met inflammasie en oksidatiewe stress. Afdoende bewys van die betrokkenheid van PON1 in vroeë KVH was egter nie gedemonstreer nie, wat die nodigheid aandui om die deelname van PON1 in latere stadiums van KVH te ondersoek.

BACKGROUND: There are many studies that have documented the increasing impact of stress and anxiety on an individual’s health and well-being. Everyone handles stress and anxiety differently with these conditions having varying physiological effects. To better recognize whether or not a person may need help in tackling these conditions, scholars have developed reliable validated instruments. Two prominent instruments that effectively assess stress and anxiety levels are the Perceived Stress (PSS) and Generalized Anxiety Disorder (GAD-7) scales. Furthermore, the literature has shed light onto the importance of the carotid intima-media thickness (c-IMT) measurement as a tool in evaluating the risk of cardiovascular disease. After all, heart disease has been reported as being the number one killer of Americans in recent years. The specific aims of this study were to determine if there was an association between perceived stress / generalized anxiety and c-IMT (static association), and also if higher levels of perceived stress / generalized anxiety result in a significant increase in c-IMT (changes over time). METHODS: Data was collected on about 700 participants comprised of employees from Emory University in Atlanta, Georgia. At baseline, six, twelve, and twenty-four months, the largest number of participants had completed and calculated their scores on the PSS and GAD-7 scales. At these same time points, participants had their IMT measured and recorded for the left and right common carotid arteries by a trained sonographer of the Emory Predictive Health Institute. Due to incomplete measurements and scores, only 228 participants were included for statistical analyses. This was still considered a suitable sample size given that this study only involved four measurement time points. Various statistical models were fitted for the data. All variables in the models were treated as categorical except for time which was continuous. Four separate models were built that included the variables perceived stress, age group, gender and time. In a similar manner, four models were built that included the variables generalized anxiety, age group, gender and time. AIC values, -2 log-likelihoods, partial correlations, p-values, and other relevant information were reported for these models. All statistical analyses were performed using the Statistical Analysis System (SAS), version 9.2. RESULTS: The mean c-IMT measurements for the Emory participants were higher than established normal ranges. A strong correlation existed between the PSS and GAD-7 two-year averages when treated as continuous variables (.7316, p <.0001). Likewise, a meaningful relationship existed when both scales were categorical (.4154, p < .0001). The analyses revealed that the left and right mean IMT measurements for the common carotid arteries modeled a linear trend with an unstructured covariance the best. The partial correlations for perceived stress and generalized anxiety revealed weak, but significant positive associations with the mean c-IMT measurement. Although the slope coefficients were not significant for perceived stress, an increase from below average to above average perceived stress level still resulted in an increase in mean c-IMT measurement. Conversely, mild generalized anxiety was found to be statistically significant in the regression model of the left mean c-IMT. This was after controlling for age group and gender. The p-value for mild generalized anxiety was 0.0258, and the slope coefficient was 0.04856. IMT measurements were consistently higher for males on both sides compared to females. They were also higher on the left side compared to the right. CONCLUSIONS: Failure to control anxiety could lead to c-IMT soaring to dangerous levels resulting in a myocardial infarction and/or cerebrovascular accident. Individuals should engage in healthy lifestyle practices that lower stress and anxiety levels to decrease the chances of cardiovascular disease. Based on this study’s findings, a person can certainly use their c-IMT readings, as well as their perceived stress and generalized anxiety scores, as indicators that lifestyle modifications may be needed.

abstract: Cardiovascular disease (CVD) is the leading cause of mortality yet largely preventable, but the key to prevention is to identify at-risk individuals before adverse events. For predicting individual CVD risk, carotid intima-media thickness (CIMT), a noninvasive ultrasound method, has proven to be valuable, offering several advantages over CT coronary artery calcium score. However, each CIMT examination includes several ultrasound videos, and interpreting each of these CIMT videos involves three operations: (1) select three enddiastolic ultrasound frames (EUF) in the video, (2) localize a region of interest (ROI) in each selected frame, and (3) trace the lumen-intima interface and the media-adventitia interface in each ROI to measure CIMT. These operations are tedious, laborious, and time consuming, a serious limitation that hinders the widespread utilization of CIMT in clinical practice. To overcome this limitation, this paper presents a new system to automate CIMT video interpretation. Our extensive experiments demonstrate that the suggested system significantly outperforms the state-of-the-art methods. The superior performance is attributable to our unified framework based on convolutional neural networks (CNNs) coupled with our informative image representation and effective post-processing of the CNN outputs, which are uniquely designed for each of the above three operations. / Dissertation/Thesis / Masters Thesis Computer Science 2016

Orientadores: Wilson Nadruz Junior, Maria Cecilia Jayme Bueno Gallani / Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T21:45:10Z (GMT). No. of bitstreams: 1 Sae_MariaCarolinaSalmoraFerreira_D.pdf: 794464 bytes, checksum: da3a843585885666b5cc119a59820102 (MD5) Previous issue date: 2010 / Resumo: O consumo elevado de sódio vem sendo amplamente estudado ao longo dos anos com o intuito de avaliar sua contribuição para o desenvolvimento de hipertensão arterial e aumento do risco cardiovascular. No entanto, pouco se sabe sobre o impacto do consumo de sódio sobre a estrutura e hemodinâmica das artérias carótidas. Desta forma, este estudo buscou investigar os efeitos do consumo de sódio sobre parâmetros estruturais e hemodinâmicos nas artérias carótidas de indivíduos hipertensos. A amostra foi composta por cento e trinta e quatro pacientes (n=134), selecionados aleatoriamente, atendidos no ambulatório de Hipertensão Arterial do Hospital de Clínicas da Universidade Estadual de Campinas - UNICAMP. O consumo diário de sódio (CDS) foi estimado pelos métodos de auto-relato: recordatório de 24 horas; consumo de sódio per capita e um questionário de freqüência alimentar - QFASó. Foram ainda obtidos dados clínicos e laboratoriais e realizado o exame ultra-sonográfico de carótidas. Os sujeitos tiveram um CDS de 5520 ± 286mg/dia. A análise univariada mostrou que o consumo diário de sódio se correlacionou com o diâmetro sistólico e diastólico da artéria carótida comum (r=0.36 e r=0.34, ambos p <0.001), tensão circunferencial de pico e média (r=0.44 e r=0.39, ambos p <0.001), Modelo de elasticidade de Young (r=0.40, p <0.001), espessura de íntima-média (r=0.19, p <0.05) e com o índice de resistência da artéria carótida interna (r=0.20, p <0.05). A análise multivariada mostrou que o consumo diário de sódio foi associado com o diâmetro da artéria carótida comum, a tensão circunferencial da parede e o modelo de elasticidade de Young. Estes dados sugerem que o consumo de sódio é um preditor independente de menor elasticidade, aumento do diâmetro da artéria e maior carga hemodinâmica local nas artérias carótidas de hipertensos / Abstract:High sodium consumption and its effect on hypertension has been widely studied over the years in an attempt to more clearly assesses its contribution for high blood pressure levels and progression of cardiovascular disease. However, little is known about the impact of dietary sodium on the structure and hemodynamics of carotid arteries. We investigated the effects of sodium intake on carotid structural and hemodynamic parameters of hypertensive subjects. The study sample was compound by one hundred third four subjects (n=134) who attended a hypertensive outpatient clinic in State University of Campinas teaching hospital, were randomly selected. Daily sodium intake was estimated by 24 hour recall, discretionary sodium and a food frequency questionnaire. Clinical history, carotid ultrasound and hemodynamic, inflammatory and metabolic parameters were also obtained. The studied sample had a daily sodium intake of 5520±286mg/day. Univariate analysis showed that daily sodium intake correlated with common carotid artery systolic and diastolic diameter (r=0.36 and r=0.34; both p<0.001), peak and mean circumferential tension (r=0.44 and r=39; both p<0.001), Young's Elastic Modulus (r=0.40, p<0.001), intima-media thickness (r=0.19, p<0.05) and with internal carotid artery resistive index (r=0.20; p<0.05). Multivariate analyses showed that daily sodium intake was associated with common carotid artery diameter, circumferential wall tension and Young's Elastic Modulus. These data suggest that sodium intake is an independent predictor of reduced elasticity, increased luminal diameter and higher local hemodynamic load in carotid arteries of hypertensive subjects / Doutorado / Ciencias Basicas / Doutor em Clínica Médica

Introduction: Atherosclerosis remains asymptomatic until it progresses to cause flow-limiting disease. Identifying patients at high risk in the early stages of the atherosclerotic process may allow modification of cardiovascular risk by effective preventive strategies. Various non-invasive tests have been studied and have shown promising results in predicting future adverse cardiovascular events. The objective of this study was to establish the carotid ultrasonographic markers that best correlate with angiographic coronary artery disease (CAD) and the relationship between left ventricular geometry, carotid atherosclerosis, biomarkers and CAD in patients with unobstructed coronary arteries, chronic stable angina (CSA) and acute coronary syndromes (ACS). Methods: Carotid ultrasound examination, echocardiography and serum biomarker estimation were performed in consecutive patients who underwent coronary angiography for evaluation of stable or acute chest pain. Results: A total of 146 subjects were recruited into the study with a mean age of 56.9 ± 10.6 (range 29 to 85) years; 120 were men (82%) and 26 (18%) women. Twenty-one percent of the study population had unobstruced coronaries, 42% had stable CAD and 37% had presented with ACS. There was no significant difference in the carotid intima media thickness (CIMT) measurements between the three groups. CIMT correlated with abnormal left ventricular geometry but not with the presence or severity of CAD. The presence of carotid plaque and plaque score correlated with obstructive CAD, but was not significantly different between stable CAD and ACS patients. There was a trend towards more echogenic plaque in the stable CAD group. The composite score of IMT and plaque was positively correlated with the presence and severity of CAD. The averaged myocardial peak systolic and early diastolic velocities were significantly lower in those with obstructive CAD. CRP and osteopontin levels were higher in the ACS patients. Conclusions: Carotid plaque and not CIMT was associated with angiographic coronary artery disease. Averaged systolic and early diastolic myocardial velocities by tissue doppler imaging correlated with obstructive CAD. Novel serum biomarkers are promising and further studies are needed.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Cardiovascular diseases (CVD) are among the top 10 causes of death in all ages in South Africa. The prevalence of maternal smoking and alcohol consumption during pregnancy is alarmingly high in South Africa. In utero exposure to nicotine and alcohol may cause CVD later in life. There is a global need for early detection of CVD especially those vulnerable during early childhood, to prevent the development of CVD risk factors in adulthood. The aim of this study was to compare CVD risk in five-year-old children from a low socio-economic population with in utero dual exposure to nicotine and alcohol and in utero nicotine exposure by measuring carotid intima-media thickness (cIMT), anthropometric measurements and clinical measurements including blood pressure. A case-control study was conducted on 468 children at five years old through interviews to collect data on demographic characteristics and health statistics. The cIMT was measured using B-mode ultrasonography. Anthropometric measurements were taken such as skinfold thickness, waist circumference, height and weight to calculate Body Mass Index (BMI). Blood pressure measurements such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were taken. The data was analysed using SPSS version 26. Descriptive and inferential statistics (Spearman’s correlations, non-parametric partial correlations), Kruskal-Wallis H, Chi-square tests and logistic regression were used for statistical analysis. Results showed a significantly higher right cIMT (RcIMT) (0.36 ± 0.05 mm; P < 0.01) in children with in utero exposure to nicotine and alcohol during pregnancy and a higher RcIMT in males (0.37 ± 0.06 mm; P < 0.01) with in utero dual exposure to nicotine and alcohol when compared to females. A significant association was found between in utero dual exposure to nicotine and alcohol and a high RcIMT, specifically in females at five years old after the adjustment for confounders (B= -1.618, P = 0.002). Consequently, females in the dual exposed group were 7.6 times more likely to exhibit higher RcIMT with a relative risk of 2.6 times greater to children with no exposure. Females also had significantly higher SBP (U= 3829.50, p <0.01), DBP (U= 3527.50, p <0.05), MAP (U= 3561.00, p <0.05) and HR (U= 3887.50, p <0.01) in the dual exposed group. Cardiovascular risk factors were modestly prevalent at five years old in children with in utero teratogen exposures. However, increased adiposity indices were not observed in this population at five years old and were not associated with teratogen exposures. This may indicate that dual exposure to nicotine and alcohol has a significant effect on the intima-media thickness of the carotid arteries in children, but not necessarily on central and peripheral adiposity at five years old. Therefore, CVD risk factors need to be identified early in children in low socioeconomic regions with in utero exposure to nicotine and alcohol to prevent CVD later in life.

Cerebral palsy (CP) is a disability that impacts a person throughout their lifespan and may place adults with the condition at an increased risk of physical inactivity and cardiovascular disease. Cardiovascular structure and function in adults with CP has not been comprehensively investigated previously. In the current cross-sectional, observational study, endothelial function, carotid distensibility, and arterial stiffness were assessed using flow-mediated dilation (FMD), B-mode ultrasound, and pulse wave velocity (PWV), respectively, in forty adults with CP (age 33.7 ± 12.7 years). The study sample was separated based on whether subjects were community ambulant or community non-ambulant using the Gross Motor Function Classification System (GMFCS). Those in GMFCS I-II were labeled community ambulant (age 31.7 ± 10.4 years) while those in GMFCS III-V were community non-ambulant (age 34.8 ± 13.6 years). Resting arterial stiffness was examined through assessment of central and upper and lower limb peripheral PWV (cPWV, uPWV, lPWV). Carotid intima-media thickness (IMT), a measure of vascular structure, was also quantified using B-mode ultrasound images and a semi-automated edge detection software program. cPWV was calculated using the distance (carotid to femoral using the subtraction method) and time delay between the foot of the carotid waveform and the foot of the femoral waveform. uPWV was calculated from the carotid to radial artery distance (subtracting the distance from the carotid to sternal notch from the carotid to radial distance) and the time delay between the arrival of the foot of each corresponding waveform. lPWV was calculated from the femoral to posterior tibialis artery using the distance between each site and time delay between the arrival of the foot of each corresponding waveform. Physical activity (PA) levels were assessed using Actigraph accelerometry with cut points that had been previously determined in normal adults. Cardiometabolic markers of fasting serum interleukin-6, insulin, glucose, and a lipid panel were analyzed. The non-ambulant group had an increased uPWV (10.2 m/s ± 1.9) compared to the ambulant group (8.28 m/s ± 1.6) (p<0.01) despite no differences in cPWV or lPWV. There were no group differences (p>0.05) in absolute, relative or normalized FMD responses. Both groups also had similar values of carotid IMT and carotid distensibility. No group differences were found in any of the cardiometabolic or inflammatory markers. Moderate-to-vigorous PA (MVPA) levels were greater in the ambulant group (2.4 mins ± 2.1 per hour) compared to the non-ambulant group (0.3 mins ± 0.6 per hour) (p<0.01). Furthermore, sedentary time was greater in the non-ambulant group (57.8 mins ± 1.9 per hour) compared to the ambulant group (51.6 mins ± 4.7 per hour) (p<0.01). Despite differences in PA levels, MVPA was not a significant independent predictor of vascular or metabolic health in this cohort of adults with CP. However, GMFCS level was predictive of both uPWV and resting heart rate. Future research should include adults with CP who are older in age to gain further insight into the potential consequences of an activity-limited lifestyle (specifically in the non-ambulant group) on cardiovascular and metabolic health in this clinical population. / Thesis / Master of Science in Kinesiology