Background: Vietnam, like other low-income countries, is facing an epidemic burden of cardiovascular disease risk factors (CVDRFs). The magnitude and directions of CVDRF progression are matters of uncertainty. Objectives: To describe the epidemiological progression of CVDRFs and the preventive effects of community lifestyle interventions, with reference to the differences in progression of CVDRF patterns between men and women. Methods: The study was conducted during 2001-2009 in nationally representative samples and in a local setting of rural areas of Ba-Vi district, Ha-Tay province. Both epidemiological and interventional approaches were applied: (i) a population-based cross-sectional survey of 2,130 people aged ≥25 years in Thai-Binh and Hanoi; (ii) an individual participant-level meta analysis of 23,563 people aged 24-74 years from multiple similar surveys in 9 provinces around Vietnam; (iii) a 17-month cohort study of 497 patients in a hypertension management programme; (iv) a quasi-experimental trial on community lifestyle promotion integrated with a hypertension management programme, evaluated by surveys of 4,645 people in both intervention and reference communes before and after a 3-year intervention. Main findings: (i) in the general adult population ≥25 years, CVDRFs were common, often clustered within individuals, and increased with age; (ii) the Vietnamese population is facing a growing epidemic of CVDRFs, which are generally not well managed; (iii) it is possible to launch a community intervention in low-resource settings within the scope of a commune-based patient-targeted programme on hypertension management; (iv) community health intervention with comprehensive healthy lifestyle promotion improves blood pressure and some behavioural CVDRFs. Conclusion: Alarming increases in CVDRFs in the general population need comprehensive multi-level prevention strategies, which combine both individual high-risk and population health approaches. The commune-based hypertension-centred management programmes integrated with community health promotion are the initial but essential steps towards comprehensive and effective management of CVDRFs and should be part of an integrated and co-ordinated national program on the prevention and control of chronic diseases in low-resource settings like Vietnam.

Background: The global burden of cardiovascular diseases (CVDs) is escalating as part of the rapid health transition that developing countries are experiencing. This increase is associated with shifts in demographics and economics, two of the major factors that affect diet and activity. The term social drift phenomenon (SDP) is used to describe the observations that: in the early stages of the epidemiological and nutrition transitions, it is usually the more affluent, higher socio–economic groups that are affected; in the later stages, it is the poor, lower socio–economic groups that display the consequences of these transitions. Therefore, in developing countries at the beginning of the transition, affluent people have higher prevalence of obesity and increased CVD risk. In developed countries, at much later stages of the transition, obesity and increased CVD risk is more prevalent in the lower socio–economic groups. In South Africa, the Transition and Health during Urbanisation of South Africans (THUSA) study which was done in 1996/1998 indicated that at that time, most of the risk factors for CVD were observed in the more urbanised (richer) subjects. It is not known if this pattern changed in any way due to the present rapid urbanisation of South African blacks. Therefore, in this study we explored the associations between socio–economic status (SES) (measured by level of urbanisation, education and employment) and CVD risk factors in an African population undergoing transition in the North–West Province of South Africa, that were prevalent in 2005 when the baseline data for in the Prospective Urban and Rural Epidemiology (PURE) study were collected. Objectives: The main objective of this dissertation was to examine the SDP in an African population in a nutrition and health transition, by: (i) Reviewing the literature on associations between socio–economic variables and biological health outcomes focusing on CVD risk factors in developed and developing countries; (ii) Analysing the baseline data from the 2005 PURE study to examine the relationships between components of SES, namely level of iii urbanisation, education and occupation, and nutrition–related CVD risk factors in men and women participating in the PURE study; and (iii) Comparing results on these associations between CVD risk factors and SES from the PURE study with those found in the THUSA study, which was conducted almost 10 years earlier, to examine if social drift in these associations has taken place. Study design: The dissertation is based on a comparison of the CVD risk factors and socio–economic status of the THUSA and PURE studies. Secondary analysis of the baseline cross–sectional epidemiological data from the PURE study was executed. The South African PURE study is part of a 12–year Prospective Urban and Rural Epidemiology study which investigates the health transition in urban and rural subjects in 22 different countries. The main selection criterion was that there should be migration stability within the chosen rural and urban communities. The rural community (A) was identified 450 km west of Potchefstroom on the highway to Botswana. A deep rural community (B), 35 km east from A and only accessible by gravel road, was also included. Both communities are still under tribal law. The urban communities (C and D) were chosen near the University in Potchefstroom. Community C was selected from Ikageng, the established part of the township next to Potchefstroom, and D from the informal settlements surrounding community C. The baseline data for PURE were collected from October to December 2005. A total of 2010 apparently healthy African volunteers (35 years and older), with no reported chronic diseases of lifestyle, tuberculosis (TB) or known human immunodeficiency virus (HIV) were recruited from a sample of 6000 randomly selected households. Methods: A variety of quantitative and qualitative research techniques was used by multidisciplinary teams to collect, measure and interpret data generated from biological samples and validated questionnaires. For this study, the statistical package for social sciences (SPSS) package (version 17.0, SPSS Inc) was used to analyze the data. Means and 95% confidence intervals (CI) of CVD risk and dietary factors were calculated. Participants of both genders were divided into different groups (according to urbanisation, education and employment levels) and compared. Estimated significant differences between rural and urban participants were determined with analysis of variance using the general linear model (GLM), multivariate procedure. Univariate analysis was used to explore further the influence of education on CVD risk factors and dietary intakes. Employment was used as a proxy for income, and pairwise comparisons using GLM, multivariate procedure were done for comparing the three groups (Not answered, employed and not employed). Tests were considered significant at P<0.05. Results: Comparison of urban with rural subjects participating in the PURE study showed that urban men had significantly higher systolic and diastolic blood pressures and lower fibrinogen levels than rural men. In women, systolic and diastolic blood pressure, fasting blood glucose and serum triglycerides were significantly higher in urban subjects whereas fibrinogen levels were significantly lower among urban subjects. After examining the relationship between the level of education and CVD risk factors, we observed that men with higher education levels had significantly higher BMI. In women, serum triglycerides and blood pressure were lower and BMI was significantly higher in the educated subjects. Because it was difficult to distinguish between reported household and individual income levels, we compared CVD risk factors of employed and unemployed subjects. Employed men had significantly higher BMI whereas the unemployed men had significantly higher fasting glucose and fibrinogen levels. Although mean blood pressure of employed men was higher than that of unemployed men, the difference did not reach significance. In women, the only significant difference seen was that employed women had lower high density lipoprotein (HDL) cholesterol, fasting glucose, triglycerides and fibrinogen levels, but they had a significantly higher BMI. Employed women had significantly higher BMI than unemployed women (27.9 [26.3–29.4] versus 26.5 [26.0–27.0] kg/m2). It seems that most of the nutrition related CVD risk factors were still higher in the higher socio–economic group, a situation similar to that reported in the THUSA study. v Conclusion: The results of this study showed little evidence of a major social drift in CVD risk factors from subjects participating in the 1996/1998 THUSA study to those in the 2005 PURE study. Most cardiovascular disease risk factors are still higher in the higher SES groups. However, there were some indications (increased fibrinogen in both men and women living in rural areas; higher triglyceride and fasting glucose levels in unemployed women; no significant differences in blood pressure and total cholesterol across different SES groups which existed in the THUSA study) that a social drift in CVD risk factors in our African population is on the way. This means that promotion of healthy, prudent diets and lifestyles should be targeted to Africans from all socio–economic levels for the prevention of CVD. / Thesis (M.Sc (Dietetics))--North-West University, Potchefstroom Campus, 2011.

Background: The global burden of cardiovascular diseases (CVDs) is escalating as part of the rapid health transition that developing countries are experiencing. This increase is associated with shifts in demographics and economics, two of the major factors that affect diet and activity. The term social drift phenomenon (SDP) is used to describe the observations that: in the early stages of the epidemiological and nutrition transitions, it is usually the more affluent, higher socio–economic groups that are affected; in the later stages, it is the poor, lower socio–economic groups that display the consequences of these transitions. Therefore, in developing countries at the beginning of the transition, affluent people have higher prevalence of obesity and increased CVD risk. In developed countries, at much later stages of the transition, obesity and increased CVD risk is more prevalent in the lower socio–economic groups. In South Africa, the Transition and Health during Urbanisation of South Africans (THUSA) study which was done in 1996/1998 indicated that at that time, most of the risk factors for CVD were observed in the more urbanised (richer) subjects. It is not known if this pattern changed in any way due to the present rapid urbanisation of South African blacks. Therefore, in this study we explored the associations between socio–economic status (SES) (measured by level of urbanisation, education and employment) and CVD risk factors in an African population undergoing transition in the North–West Province of South Africa, that were prevalent in 2005 when the baseline data for in the Prospective Urban and Rural Epidemiology (PURE) study were collected. Objectives: The main objective of this dissertation was to examine the SDP in an African population in a nutrition and health transition, by: (i) Reviewing the literature on associations between socio–economic variables and biological health outcomes focusing on CVD risk factors in developed and developing countries; (ii) Analysing the baseline data from the 2005 PURE study to examine the relationships between components of SES, namely level of iii urbanisation, education and occupation, and nutrition–related CVD risk factors in men and women participating in the PURE study; and (iii) Comparing results on these associations between CVD risk factors and SES from the PURE study with those found in the THUSA study, which was conducted almost 10 years earlier, to examine if social drift in these associations has taken place. Study design: The dissertation is based on a comparison of the CVD risk factors and socio–economic status of the THUSA and PURE studies. Secondary analysis of the baseline cross–sectional epidemiological data from the PURE study was executed. The South African PURE study is part of a 12–year Prospective Urban and Rural Epidemiology study which investigates the health transition in urban and rural subjects in 22 different countries. The main selection criterion was that there should be migration stability within the chosen rural and urban communities. The rural community (A) was identified 450 km west of Potchefstroom on the highway to Botswana. A deep rural community (B), 35 km east from A and only accessible by gravel road, was also included. Both communities are still under tribal law. The urban communities (C and D) were chosen near the University in Potchefstroom. Community C was selected from Ikageng, the established part of the township next to Potchefstroom, and D from the informal settlements surrounding community C. The baseline data for PURE were collected from October to December 2005. A total of 2010 apparently healthy African volunteers (35 years and older), with no reported chronic diseases of lifestyle, tuberculosis (TB) or known human immunodeficiency virus (HIV) were recruited from a sample of 6000 randomly selected households. Methods: A variety of quantitative and qualitative research techniques was used by multidisciplinary teams to collect, measure and interpret data generated from biological samples and validated questionnaires. For this study, the statistical package for social sciences (SPSS) package (version 17.0, SPSS Inc) was used to analyze the data. Means and 95% confidence intervals (CI) of CVD risk and dietary factors were calculated. Participants of both genders were divided into different groups (according to urbanisation, education and employment levels) and compared. Estimated significant differences between rural and urban participants were determined with analysis of variance using the general linear model (GLM), multivariate procedure. Univariate analysis was used to explore further the influence of education on CVD risk factors and dietary intakes. Employment was used as a proxy for income, and pairwise comparisons using GLM, multivariate procedure were done for comparing the three groups (Not answered, employed and not employed). Tests were considered significant at P<0.05. Results: Comparison of urban with rural subjects participating in the PURE study showed that urban men had significantly higher systolic and diastolic blood pressures and lower fibrinogen levels than rural men. In women, systolic and diastolic blood pressure, fasting blood glucose and serum triglycerides were significantly higher in urban subjects whereas fibrinogen levels were significantly lower among urban subjects. After examining the relationship between the level of education and CVD risk factors, we observed that men with higher education levels had significantly higher BMI. In women, serum triglycerides and blood pressure were lower and BMI was significantly higher in the educated subjects. Because it was difficult to distinguish between reported household and individual income levels, we compared CVD risk factors of employed and unemployed subjects. Employed men had significantly higher BMI whereas the unemployed men had significantly higher fasting glucose and fibrinogen levels. Although mean blood pressure of employed men was higher than that of unemployed men, the difference did not reach significance. In women, the only significant difference seen was that employed women had lower high density lipoprotein (HDL) cholesterol, fasting glucose, triglycerides and fibrinogen levels, but they had a significantly higher BMI. Employed women had significantly higher BMI than unemployed women (27.9 [26.3–29.4] versus 26.5 [26.0–27.0] kg/m2). It seems that most of the nutrition related CVD risk factors were still higher in the higher socio–economic group, a situation similar to that reported in the THUSA study. v Conclusion: The results of this study showed little evidence of a major social drift in CVD risk factors from subjects participating in the 1996/1998 THUSA study to those in the 2005 PURE study. Most cardiovascular disease risk factors are still higher in the higher SES groups. However, there were some indications (increased fibrinogen in both men and women living in rural areas; higher triglyceride and fasting glucose levels in unemployed women; no significant differences in blood pressure and total cholesterol across different SES groups which existed in the THUSA study) that a social drift in CVD risk factors in our African population is on the way. This means that promotion of healthy, prudent diets and lifestyles should be targeted to Africans from all socio–economic levels for the prevention of CVD. / Thesis (M.Sc (Dietetics))--North-West University, Potchefstroom Campus, 2011.

Abstract Cardiovascular diseases (CVD), and especially atherosclerotic vascular diseases (ASVD), are the largest cause of morbidity and premature death worldwide. Coronary heart disease (CHD) and cerebrovascular disease (stroke) are common and severe manifestations of ASVD. Atherosclerosis is a chronic inflammatory disease and lipoprotein metabolism disorder. If the regulation of inflammatory process is disturbed, the systemic release of pro-inflammatory mediators, including matrix metalloproteinases (MMPs), may lead to a low-grade systemic inflammation, which is a risk factor for CVDs. MMPs are enzymes that are responsible for the degradation of the extracellular matrix (ECM) during growth and tissue renewal but also in many pathological conditions. These ECM degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture, leading to acute cardiovascular manifestations. The pivotal role of MMPs in atherosclerosis has raised interest in the development of drug therapies targeting these proteases. Doxycycline has inhibitory effects on some MMPs in addition to its antimicrobial properties. The main objective of this thesis project was to investigate the potential of these inflammatory mediators as biomarkers, risk factors, and therapeutic targets in CVD. The special focus was on MMP-8 and its main regulator, tissue inhibitor of matrix metalloproteinase (TIMP)-1. The results of this study show that a high serum MMP-8 concentration indicates an acute cardiac condition and predicts a future CVD event. In addition to MMP-8, MMP-7 is a potential biomarker for incident CVD. The balance between these MMPs and their tissue inhibitor may indicate vulnerability to plaque rupture. Measurement of serum MMP-8 concentration is reliable, anti-invasive and inexpensive and can be done in hospital settings. We also show that regular-dose doxycycline decreases the systemic inflammatory burden in patients with earlier myocardial infarction and is a promising anti-inflammatory therapy in the prevention of CVDs with relatively minor side effects. In conclusion, MMP-8 and TIMP-1 can be considered inflammatory risk markers of CVD events and death, and they can be utilized both for diagnostic and screening purposes. The inhibition of MMP-8 by doxycycline may reduce the systemic inflammatory burden in patients with myocardial infarction. / Tiivistelmä Sydän- ja verisuonisairaudet, erityisesti ateroskleroottiset valtimosairaudet, ovat maailman yleisin sairastuvuuden ja ennenaikaisen kuoleman syy. Sepelvaltimotauti ja aivohaveri ovat ateroskleroottisen valtimosairauden yleisiä ja vakavia ilmenemismuotoja. Ateroskleroosi on krooninen tulehduksellinen sairaus ja lipoproteiiniaineenvaihdunnan häiriö. Jos tulehdustapahtuma häiriintyy, elimistöön vapautuvat tulehdusvälittäjäaineet, kuten matriksin metalloproteinaasit (MMP), voivat aiheuttaa elimistön matala-asteisen tulehduksen, joka on sydän- ja verisuonisairauksien riskitekijä. MMP:t ovat entsyymejä, jotka pilkkovat solunväliainetta kasvun ja kudosten uusiutumisen mutta myös monien tautitilojen yhteydessä. Nämä soluväliainetta hajottavat proteaasit ja niiden säätelijät ovat tärkeässä roolissa ateroskleroottisen plakin muodostumisessa ja repeämisessä, joka johtaa äkillisiin sydäntautitapahtumiin. Matriksin metalloproteinaasien keskeinen rooli ateroskleroosissa on herättänyt kiinnostusta niihin kohdistuvan lääkehoidon kehittämiseen. Doksisykliinillä on joidenkin MMP-entsyymien toimintaa estävä vaikutus antimikrobiaalisten ominaisuuksiensa lisäksi. Tämän väitöskirjatutkimuksen päätavoitteena oli tutkia näiden tulehdusvälittäjäaineiden mahdollisuuksia biomarkkereina, riskitekijöinä ja lääkehoidon kohteena sydän- ja verisuonisairauksissa. Erityinen kiinnostuksen kohde oli MMP-8 ja sen pääsäätelijä ja kudosestäjä, tissue inhibitor of matrix metalloproteinase (TIMP)-1. Tämän tutkimuksen tulokset osoittavat, että seerumin korkea MMP 8 pitoisuus viittaa akuuttiin sydäntautiin ja ennakoi tulevaa sydäntautitapahtumaa. MMP-8:n lisäksi MMP-7 on lupaava sydäntapahtuman biomarkkeri. Näiden matriksin metalloproteinaasien ja niiden kudossäätelijä TIMP-1:n välinen tasapaino voi liittyä ateroskleroottisen plakin haurauteen. Seerumin MMP-8:n mittaus on luotettavaa, kajoamatonta ja edullista, ja mahdollista toteuttaa myös sairaalaolosuhteissa. Näytämme myös, että doksisykliini vähentää elimistön tulehdustaakkaa sydäninfarktin sairastaneilla potilailla ja että se on sydäntautien ehkäisyssä lupaava anti-inflammatorinen lääke, jolla on suhteellisen vähän sivuvaikutuksia. Johtopäätöksenä on, että MMP-8:aa ja TIMP-1:tä voidaan pitää lupaavina sydän- ja verisuonitautien sekä kuoleman biomarkkereina sekä diagnostiikka- että seulontakäytössä. Lisäksi tutkimustulokset osoittavat, että MMP-8:n esto doksisykliinillä voi vähentää elimistön tulehdustaakkaa sydänkohtauksen sairastaneilla potilailla.

Patients with chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) experience premature cardiovascular mortality and morbidity compared with the general population. The increased risk of cardiovascular disease (CVD) may in part, result from an interaction between traditional and non-traditional risk factors, modulated by chronic inflammation. The aim of this project was to look at lipid associated biomarkers in patients with SLE/RA and the association between these markers and cardiovascular disease outcomes. We also aimed to study the effect of inflammation reduction on vascular biomarkers. In the first study we examined 168 SLE patients median (IQR) age was 53 (46-61) years and median disease duration 13 (7, 23) years and 56 healthy controls median age 50 (39-60) years. We demonstrated elevated level of oxidised-LDLin SLE patients compared with healthy controls (76 (57, 99) U/l vs 56 (42, 88)U/l P= 0.02). We further explored the association between oxidant stress and premature atherosclerosis as measured by carotid intima media thickness (cIMT) and plaque. In addition to age and systolic blood pressure, oxidised-LDL and urinary 8-isoprostane were significantly and independently associated with cIMTin SLE patients _ coefficient 95%CI [0.00007 (5.29−6, 0.0001) and 0.003 (0.0008,0.004)], respectively. In healthy controls, age was the only independent variable. In the Norfolk Arthritis Register, 1266 patients with early inflammatory polyarthritis (IP) were studied. A linear regression analysis revealed a significant negative association between CRP and lipid profile namely TC, LDL, TG and ApoA-1. During a median (IQR) follow up = 5.5 (3.7-7.7) years 100 (7%) patients died (all causes) of which 33% (33) deaths were attributed to CVD. Forward stepwise regression analysis demonstrated that a low total cholesterol was independently associated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) and CVD mortality HR (95%CI) 0.49 (0.29, 0.85). In a small cohort 27 SLE patients and 15 healthy controls. We measured endothelial function using flow mediated dilatation of the brachial artery. At baseline we found a significant increase in TG level [1.36 (0.9, 1.87) mmol/l vs0.88 (0.64, 1) mmol/l P= 0.009] and a significant impaired endothelial function in SLE patients compared to the healthy controls [2.86 (0.6, 5.3) vs 6.81 (3.46,8.57), P= 0.03]. After treatment, there was a trend towards reduced TG level and improved endothelial function. Oxidised-LDL did not change significantly. In conclusion, oxidant stress is increased in SLE patients and relates to some measures of subclinical atherosclerosis. Control of inflammation may not be sufficient to completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low total cholesterol may be the best biomarker of the overall metabolic and inflammatory status of the patients as well as indicating a group with increased risk of future mortality.

Thesis (MPH.) -- University of Limpopo, 2019 / The purpose of this study was to profile selected cardiovascular disease risk factors among HIV patients on ART in Bushbuckridge sub-district. Quantitative, crosssectional research was conducted to describe cardiovascular disease risk factors among HIV patients on ART in Bushbuckridge Sub-district. Data collection was done using researcher-administered questionnaires. Adult HIV patient on ART participated in the study (n=328). The study has highlighted cardiovascular disease risk factors and prevalence of cardiovascular disease risk factors among HIV patients on ART. The findings revealed the prevalence of hypertension is 34.6% among HIV patients on ART and men had a higher prevalence compared to women. There is an increase in body mass index and it is seen mostly among women. Alcohol consumption is highest in the young adults (18 to 24 years) both men and women. Health promotion and policymaking interventions need to improve strategies on management and prevention of cardiovascular disease risk factors. Key concepts HIV, ART, cardiovascular disease risk factors, prevalence, body mass index, Bushbuckridge

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015

The IDSA Community-Acquired Pneumonia (CAP) Guideline recommends ceftriaxone in combination with doxycycline as an alternative to combination therapy with ceftriaxone and azithromycin for non-intensive care unit (ICU) patients hospitalized with CAP. This is an attractive alternative regimen due to recent concerns of increased cardiovascular risk associated with azithromycin. The objective of this study was to compare the clinical outcomes of azithromycin and doxycycline each in combination with ceftriaxone for non-ICU Veterans hospitalized with CAP.

<p>Accumulating evidence from randomized-controlled, full-feeding trials suggests neutral to beneficial effects of consuming lean and unprocessed red meat within a healthy dietary pattern on cardiovascular health. It is unclear how red meat interacts with the dietary pattern and the host in mediating its health effects. The gut microbiome provides a novel perspective in understanding the diet-host relationship for its abilities to metabolize dietary components including those within red meat and influence cardiovascular health. Prior to starting our study, we identified a lack of evidence in the English literature for the effects of consuming lean red meat, in unprocessed or processed forms, on gut microbiota in the context of a controlled healthy dietary pattern. Our findings presented in this dissertation demonstrate differential effects of consuming unprocessed versus processed red meat on gut microbiota. Consistent with previous research, we observed cardiovascular improvements induced by the healthy dietary pattern independent of lean red meat intakes among young adults with apparently healthy cardiovascular profiles. Importantly, with three intervention periods, we found consistent and reproducible changes in both gut microbiota and cardiovascular risk factors when repeatedly adopting and abandoning a healthy dietary pattern. Collectively, findings in this dissertation highlight the importance of gut microbiota in potentially mediating or responding to diet-induced cardiovascular improvements. Future research should investigate the changes in the function of gut microbiota induced by healthy dietary patterns containing red meat. Studies assessing the unique food matrix of processed versus unprocessed animal- or plant-based protein-rich foods are also warranted. Additionally, dietary strategies should focus on promoting healthy dietary modifications and enhancing dietary adherence for long-term cardiovascular benefits. </p>