Despite advances, stroke remains the largest cause of disability and fourth leading cause of death in the United States. The relationship between changes in human vasculature (atherosclerosis and arteriosclerosis) prior to clinical incident, and other risk factors for stroke remains unclear. This dissertation represents work towards the identification of imaging biomarkers for vascular change, focusing on ultrasound to characterize persons at risk, including differences among race/ethnic groups. This research contained three distinct projects. The first goal was to determine if changes within ultrasonographic measures of carotid vasculature could be found across race/ethnic groups after adjustment for risk factors. The second was to determine if those same measures were related to changes in cerebral white matter known to be associated with ongoing cerebrovascular disease; we compared ultrasound to an MRI marker of subclinical vascular disease, white matter hyperintensity volume (WMHV). Finally, we sought to investigate a known and well-studied ultrasound marker for atherosclerosis, carotid intima-medial thickness, with those same MRI markers of subclinical vascular disease (WMHV). All studies were conducted within an on-going multiethnic cohort that has been followed since 1990, The Northern Manhattan Study. The population is comprised of persons who self-identify as Hispanic (52%), Black (24%), or White (21%), with less than 3% identified as “race/other.” We found race/ethnic differences in carotid arterial stiffness and diameter; carotid diameter increases with age among Hispanics, but not among blacks or whites. A significant correlation was also found between diastolic diameter and subclinical vascular disease, and this relationship was also increased among Hispanics; neither black race nor white race was associated with corresponding increases in both MRI white matter hyperintensity and diastolic diameter. Finally, using a surrogate marker for atherosclerosis, carotid intima-medial thickness (cIMT), we document for the first time, positive associations between cIMT and WMHV. There are important developments still to be made in the field of vascular risk. Use of inexpensive and non-invasive ultrasound technology to approximate ongoing cerebrovascular disease could lead to better understanding of the effect of known risk factors, and could help stroke risk assessment and treatment modification.

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.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Bakgrund: Sjuksköterskeyrket är ett kvinnodominerat yrke. I Sverige är ca 90 % av sjuksköterskorna kvinnor. Att utföra intima omvårdnadsåtgärder är en viktig del av sjuksköterskans arbete. Intima omvårdnadshandlingar är situationer då patienten blir exponerad på ett, för denna, intimt sätt. Både manliga och kvinnliga sjuksköterskor framhåller att det är en stor utmaning för dem att utföra dessa omvårdnadshandlingar på ett, för patienten, korrekt sätt.   Syfte: Att beskriva patienters inställning till intima omvårdnadshandlingar utfört av sjuksköterskor av motsatt kön. Metod: Litteraturöversikt enligt Friberg (2012). Litteraturöversikten är baserad på 11 vetenskapliga artiklar varav 6 är har kvantitativ design, 4 kvalitativ och 1 mixad metod. Artiklarna är framtagna genom sökning i databaserna CINAHL Complete och Academic Search Complete. Resultat: Resultatet presenteras i tre teman. I Patienter föredrar kvinnliga sjuksköterskor vid intima omvårdnadshandlingar framgår att patienter av båda könen helst ser att en kvinnlig sjuksköterska utför de intima omvårdnadshandlingarna. I Patienters inställning till sjuksköterskor som förkläden visar resultatet att det råder delade meningar hur patienten vill använda sig av ett förkläde eller ej. I det sista temat, Patientens inställning till sjuksköterskan och vårdrelationen vid intima omvårdnadshandlingar framkommer patienternas åsikter kring vad som är en professionell sjuksköterska och hur denna kan agera för att stärka vårdrelationen. Diskussion: Diskussionen delas upp i två teman, varför föredrar patienter kvinnliga sjuksköterskor samt Hur kan sjuksköterskan använda vårdrelation för att underlätta mötet vid intima omvårdnadshandlingar.  Resultatet diskuteras utefter konsensusbegreppet vårdande samt begreppet vårdrelation. / Background: The nursing profession is a female dominated profession. About 90 % of the nurses, in Sweden, are female. To perform intimate care is a vital part of  nurses’ work. Intimate care situations where the patient gets exposed in an intimate way e.g through undressing. Both male and female nurses emphasize intimate care activities to be challenging to perform, in a correct way. Aim: To describe patient attitudes towards intimate care performed by female or male nurses. Method: Literature review according to Friberg (2012). This literature review is based on 11 scientific articles of which 6 were of a quantitative design, 4 are of qualitative design and 1 of a mixed method. The articles were found through a search in CINAHL Complete and Academic Search Complete databases. Results: The results are presented in three themes. In patients prefer female nurses to perform intimate care it becomes evident that patients of both sex prefer a female nurse to perform the intimate care. In patients attitudes towards nurses as chaperones the results show differences in attitudes amongst patients about the usage of chaperones or not. In the final theme, patients attitudes towards nurse and the care relationship in intimate care, shows patients attitudes about what constitute a professional nurse and how they can facilitate a strengthened care relationship. Discussion: The discussion is divided in two themes, why do patients prefer female nurses and how can nurses use the care relationship to ease the encounter with intimate care. The results are discussed in relation to the concepts caring and care relationship.