Cardiovascular disease (CVD) is a major cause of adult morbidity and mortality in developed as well as in developing countries. In black population groups, stroke is more prominent than ischaemic heart disease. This may be attributed to a combination of risk factors seen in this population group inter alia raised haemostatic markers, which favour the development of stroke since it is well known that a disturbance in the haemostatic balance (a hypercoagulable and a hypofibrinolytic state) predisposes to CVD. It is generally accepted that childhood genetic, environmental and behavioural factors lay the groundwork for the manifestation of adult CVD. Therefore, one of the studies that form part of this dissertation was a cross-sectional study to determine whether haemostatic abnormalities are already present in black African adolescents and to determine whether high risk groups exist [in relation to the following haemostatic markers: fibrinogen, factor VIII (FVIII), plasminogen activator inhibitor type 1 activity (PAI-Iact), and thrombin anti-thrombin complex (TAT)] for the development of CVD later in life. The population subdivisions were made according to gender, body fat %, maturity status, height for age Z-score, and habitual PA levels. Since behavioural factors [diet, physical activity (PA), smoking and drinking habits] are controllable determinants, it could be possible to improve CVD risk to a certain degree. Therefore, the second study that forms part of this dissertation attempted to establish whether a PA programme will successfully reduce haemostatic variables in a subset of the study population used in the first study. The reader is referred to the abstracts at the beginning of each separate study manuscript (Chapters 3 and 4), for a description of the subjects, study design and methods used in each study. The results of the cross-sectional study showed that in African adolescents (a) gender independently contributed to the variability in PAI-Iact, but that the gender difference in fibrinogen and TAT could be explained by the significant differences in fat mass and PA levels observed between the genders; (b) fibrinogen was significantly higher in the stunted compared to the non-stunted children indicating that childhood chronic malnutrition may possibly predispose independently to CVD; (c) fitness influences TAT concentrations positively and that (d) no significant differences in FVIII could be found between any of the subdivisions. As these determinants seem to be modifiable through behavioural changes and optimal nutrition status through early life, it raises a sense of urgency to develop strategies for the prevention and treatment of these risk factors. The results of the intervention study showed that an 11-week outdoor PA intervention programme had no significant effect on the haemostatic markers of African adolescents, but the results of this study should be interpreted with caution since (a) seasonal variations could have clouded the effect of the PA intervention as baseline measurements were taken in the summer and end measurements in the winter; (b) attendance of the PA sessions does not necessarily implicate compliance to the exercises given; (c) baseline values seem to play a prominent role in the changes that could be expected during an intervention and, therefore, improvements in the haemostatic profile would most likely be more significant in individuals with raised baseline levels. Similar research on African children is warranted since studies investigating PA's effect on haemostatic variables remain a topic of debate and speculation and data on African population groups are scanty. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

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.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

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: Rheumatoid arthritis (RA) is characterised by excessive production of tumour necrosis factor alpha (TNFα). This leads to rheumatoid cachexia, a condition characterised by increased resting energy expenditure (REE) and loss of fat-free mass (FFM) leading to functional disability, decreased strength and balance. The aims of this research work was to: a) to develop a new REE equation in order to continuously monitor abnormal changes in REE in the RA population, b) to investigate if smoking further enhances hypermetabolism and c) to examine if the new anti-TNFα medication reverses this metabolic abnormality. Methods: 68 patients with RA were assessed for demographic and anthropometrical characteristics, REE (indirect calorimetry), body composition (bioelectrical impedance), and disease activity [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score 28 (DAS28) and health assessment questionnaire (HAQ)]. 20 of the total 68 patients, about to start anti-TNFα therapy, underwent the exact same aforementioned procedures but on three separate occasions (Baseline: two weeks prior to anti-TNFα treatment, Time-1 and Time-2: two weeks and three months, respectively, after the drug had been introduced. Results: Study 1: Based on FFM and CRP, a new equation was developed which had a prediction power of R2=0.76. The new equation revealed an almost identical mean with measured REE (1645.2±315.2 and 1645.5±363.1 kcal/day, p>0.05), and a correlation coefficient of r=0.87 (p=0.001). Study 2: Smokers with RA demonstrated significantly higher REE (1513.9±263.3 vs. 1718.1±209.2 kcal/day; p=0.000) and worse HAQ (1.0±0.8 vs. 1.7±0.8; p=0.01) compared to age and FFM matched RA non-smokers. The REE difference was significantly predicted by the interaction smoking/gender (p=0.04). Study 3: Significant increases were observed in REE (p=0.002), physical activity (p=0.001) and protein intake (p=0.001) between the three times of assessment. Moreover, disease activity significantly reduced [ESR (p=0.002), DAS28 (p=0.000), HAQ (p=0.000) and TNFα (p=0.024)] while FFM and total body fat did not change (both at p>0.05). Physical activity and protein intake were found to be significant within-subject factors for the observed REE elevation after 12-weeks on anti-TNFα treatment (p=0.001 and p=0.024, respectively). Conclusions: Findings from the first study revealed that the newly developed REE equation provides an accurate prediction of REE in RA patients. Moreover, the results from the second study showed that cigarette smoking further increases REE in patients with RA and has a negative impact on patients’ self-reported functional status. Finally, our data from the third study suggest that REE remains elevated not because of the maintenance of the RA-related hypermetabolism but due to the concomitant significant increases in physical activity and protein intake.

Stroke and myocardial infarction (MI) are serious conditions whose burdens vary by socio-demographic and geographic factors. Although several studies have investigated and identified disparities in burdens of these conditions at the county and state levels, little is known regarding their geographic epidemiology at the neighborhood level. Both conditions require emergency treatments and therefore timely geographic accessibility to appropriate care is critical. Investigation of disparities in geographic accessibility to stroke and MI care and the role of Emergency Medical Services (EMS) in reducing treatment delays are vital in improving health outcomes. Therefore, the objectives of this work were to: (i) classify neighborhoods based on socio-demographic and geographic characteristics; (ii) investigate spatial patterns of neighborhood level mortality; (iii) identify disparities in geographic accessibility to stroke and MI care; and (iv) identify disparities in EMS transport times for stroke and MI patients in East Tennessee. Fuzzy cluster analysis was used to classify neighborhoods into peer neighborhoods (PNs) based on their socio-demographic and geographic factors. Neighborhood level spatial patterns of stroke and MI mortality risks were investigated using Spatial Empirical Bayesian smoothing techniques and neighborhoods with high mortality risks identified using spatial scan statistics. Travel times to stroke and cardiac care facilities were computed using network analysis to investigate geographic accessibility. Records of over 3,900 suspected stroke and MI patients, from two EMS providers, were used to investigate disparities in EMS transport delays. Four distinct PNs were identified. The highest stroke/MI mortality risks were observed in less affluent, urban PNs, and lowest risks in more affluent, suburban PNs. Several significant (p<0.0001) stroke and MI high mortality risk spatial clusters were identified. Approximately 8% and 15% of the population did not have timely accessibility to appropriate stroke and MI care, respectively. The disparity was greatest for populations in rural areas. Important disparities in EMS transport delays were identified, with the travel time to a hospital contributing the longest delay. The identified disparities in neighborhood characteristics, mortality risks, geographic accessibility, and EMS transport delays are invaluable in guiding resource allocation, service provision, and policy decisions to support evidence-based population health planning and policy.

Objectives. To study whether birth weight (BW) was correlated to cardiovascular risk factors, coronary heart disease (CHD), cardiovascular disease (CVD), and prostate cancer (PCA) at adult ages, whether a possible relationship depended on mediating factors from birth time, hereditary circumstances, and adult life variables, and what importance possible associations might have for the rate of the complaint in the general population. Material and methods. Population-based cohorts of men born in 1913 and followed up until old age. Risk of outcome was estimated using Cox’s and Poisson regressions. The results were transformed to population attributable risk percentage (PAR%) of the complaint that could be attributed to low or high BW, given causality between exposure and outcome. Results. After adjustment for the influence of covariates, systolic blood pressure at age 50 decreased by 3.7 mmHg per 1000 g increase in BW, the prevalence of antihypertensive treatment decreased by 32%, diabetes by 53%, serum total cholesterol decreased by 0.20 mmol L-1, and being in top quintile of serum cholesterol decreased by 23%. The adjusted risks were somewhat more marked relative to the crude risks. CHD and CVD incidence and mortality were virtually unaffected by BW. In the general population, the risk percentage attributable to a BW ≤3000 g was 18% for diabetes, 2.5% for cholesterol, and ≤1% for antihypertensive treatment and CHD and CVD incidence and mortality. PCA incidence and mortality risk increased by 62% and 82%, respectively, among those whose BW was ≥4250 g compared with those whose BW was 3001-4249 g. The risk percentages attributable to a BW ≥4250 g in the general population for PCA incidence and mortality were 7.8% and 10.8%. Conclusions. Low BW seemed to affect cardiovascular risk factors but not incidence and mortality from CHD and CVD. A high proportion of diabetes on the community level could be attributed to low BW, while the proportional burden of other cardiovascular complaints that could be attributed to low BW was modest. PCA incidence and mortality seemed to be affected by high BW.

Despite major advances in the treatment and prevention of atherosclerosis the last several decades, cardiovascular disease still accounts for the majority of deaths in Sweden. With the population getting older, more obese and with rising numbers of diabetics, the cardiovascular disease burden may increase further in the future. The focus in cardiovascular disease has shifted with time from calcification and narrowing of arteries to the biological processes within the atherosclerotic plaque. C-reactive protein (CRP) has emerged as one of many proteins that reflect a low grade systemic inflammation and is suitable for analysis as it is more stable and easily measured than most other inflammatory markers. Several large prospective studies have shown that CRP is not only an inflammatory marker, but even a predictive marker for cardiovascular disease. C-reactive protein is associated with several other risk factors for cardiovascular disease including obesity and the metabolic syndrome. Our study of twenty healthy men during a two week endurance cross country skiing tour demonstrated a decline in already low baseline CRP levels immediately after the tour and six weeks later. In a study of 200 obese individuals with impaired glucose tolerance randomised to a counselling session at their health care centre or a one month stay at a wellness centre, we found decreased levels of CRP in subjects admitted to the wellness centre. The effect remained at one, but not after three years of follow-up. In a prospective, nested, case-referent study with 308 ischemic strokes, 61 intracerebral haemorrhages and 735 matched referents, CRP was associated with ischemic stroke in both uni- and multivariate analyses. No association was found with intracerebral haemorrhages. When classifying ischemic stroke according to TOAST criteria, CRP was associated with small vessel disease. The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP, but neither with ischemic stroke nor with intracerebral haemorrhage. A study on 129 patients with atrial fibrillation was used to evaluate whether inflammation sensitive fibrinolytic variables adjusted for CRP could predict recurrence of atrial fibrillation after electrical cardioversion. In multivariate iv models, lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP and markers of the metabolic syndrome. In conclusion, lifestyle intervention can be used to reduce CRP levels, but it remains a challenge to maintain this effect. CRP is a marker of ischemic stroke, but there are no significant associations between the CRP1444 polymorphism and any stroke subtype, suggesting that the CRP relationship with ischemic stroke is not causal. The fibrinolytic variable, PAI-1, is associated with the risk of recurrence of atrial fibrillation after electrical cardioversion after adjustment for CRP. Our findings suggest a pathophysiological link between atrial fibrillation and PAI-1, but the relation to inflammation remains unclear.

Cardiovascular disease (CVD) is one of the major health issues of our time. The prevalence of CVD is increasing, both in industrialized and in developing countries, and causes suffering and a decreased quality of life for millions of people worldwide. CVD can have multiple etiologies, but the main underlying cause is atherosclerosis, which causes blood clot formation and obstructs vital arteries. Multiple risk factors of atherosclerosis have been identified, and body fatness is one of the most important ones.  The main aims of this thesis were to investigate the relation between body fatness and: CVD risk factors (paper I), incident stroke (paper II), and overall mortality (paper III). The results showed that abdominal obesity is strongly associated with both CVD risk factors and stroke incidence (papers I-II). The results also suggested that a substantial part of the association between increased body fat and stroke can be explained by an increase in traditional stroke risk factors associated with increased body fat (paper II). A gynoid fat distribution, with a high share of fat located around the hip, is, on the other hand, associated with lower risk factor levels in both men and women, and with a decreased risk of stroke in women (papers I-II). This illustrates the importance of assessing the overall distribution of body fat rather, than solely focusing on total body fatness. In elderly women, total body fat was found to be associated with increased survival, while abdominal fat moderately increased mortality risk (paper III). Lean mass (fat-free mass) was strongly associated with increased survival among elderly men and women (paper III). Erythrocyte sedimentation rate (ESR) is an indicator of inflammation and, possibly, an indicator of atherosclerotic disease. In paper IV, the relationship between ESR in young adulthood and the later risk of myocardial infarction (MI) was studied. Results showed that higher levels of ESR were associated with a higher MI risk, in a dose-responsive manner, and was independent of other well-established risk factors. In summary, both total and regional fat distribution are associated with CVD risk factors and stroke, but do not seem to correspond to an increase in mortality risk among the elderly. Also, inflammation, detected as an increase in ESR, is associated with long term MI risk in young men.