Kawasaki disease (KD) is the most common cause of paediatric acquired heart disease which may be attributed to the combined effects of infection, immunological response, and genetic susceptibility. Acute coronary artery lesions (CALs) develop in 20-48 % KD children. In addition, chronic CALs develop in approximately 20-30% of untreated KD children. Although KD children treated with IVIG, 2-6% still develop chronic CALs. According to recent epidemiological studies, Asian populations have a much higher incidence of KD. Taiwan has the third highest annual incidence in the world (69 per 100,000 children < 5 years of age between 2003 and 2006). Several studies have shown that KD patients spontaneously produce high levels of IL- 10. Plasma or serum IL-10 levels of KD children in acute phase were nearly 8-33 fold and 4-5 fold higher than those of healthy controls and those of the acute febrile children, respectively. The elevated IL-10 levels during the acute phase of KD not only decreased during subacute and convalescent phase, but also decreased immediately after IVIG administration, coincidently rapid improvement of inflammatory symptoms. The above studies show a correlation of high IL-10 levels with inflammatory features of KD, but do not answer the question of whether high levels of IL-10 may be simply a byproduct of acute KD, or whether it may play a role in the pathogenesis of KD. Therefore, a family-based linkage study of 134 case-parents trios, a case-control study of 247 KD children and 129 normal controls, and a matched case-control study of 76 KD cases with acute coronary artery lesions (CALs) and 76 KD controls without acute CALs were carried out to evaluate the association of genetic single nucleotide polymorphisms (SNP) in IL-10 promoter (-1082, -819, and -592) with the risk of KD and acute CALs. Based on the Transmission Disequilibrium test (TDT) results, significant undertransmission of haplotype ATA and overtransmission of haplotype (ACC+GCC) were found for KD (p = 0.023 and 0.011, respectively), even after 1,000 times permutation (p = 0.026 and 0.010, respectively). In addition, the TC and CC genotype of IL-10-819T>C were significantly associated with the decreased risk of acute CALs (AOR, 0.93; 95% CI, 0.47-1.81 and AOR, 0.07; 95% CI, 0.01-0.62, respectively), as compared to TT genotype. The carries of AC and CC genotype in IL-10-592A>C were with significantly decreased risk of acute CALs (AOR, 0.90; 95%CI, 0.46-1.75 and AOR, 0.17; 95%CI, 0.03-0.87, respectively), as compared to those with AA genotype. Furthermore, as compared with ATA/ATA diplotype, GCC+ACC/GCC+ACC diplotype of IL10 was associated with the decreased risk of acute CALs (AOR, 0.18; 95% CI, 0.04-0.72). In conclusion, the haplotype and diplotype of IL10-1082/-819/-592 were significant differences in the transmission in KD families and that the IL10-819 and -592 SNPs played important role for the sequelae of acute CALs.

Mental stress ischemia (MSI) is associated with poor prognosis for coronary artery disease (CAD) and is amenable to treatment, yet no easily administered test exists to diagnose it. Given the known increase in systemic vascular tone in response to stress, we studied the ability of peripheral arterial tonometry (PAT), a noninvasive functional measure of arterial tone, to predict those vulnerable to MSI. Seventy-seven patients with chronic stable CAD were subjected to mental stress with concomitant assessment of myocardial perfusion and pulse wave amplitude. Nuclear perfusion imaging was used to document MSI, and PAT was used to measure pulse wave and microarterial tone. A ratio of PAT measurements during stress to those before stress was used to characterize vascular responses. Serum catecholamines and endothelin-1 (ET-1) were simultaneously measured. Subjects who experienced MSI had a lower average PAT ratio than those who did not (0.76 ¡À 0.04 vs. 0.91 ¡À 0.05, P = 0.03). A receiver operating characteristics curve for PAT ratio predicting MSI had an area under the curve of 0.613 (standard error, 0.065, one-sided P = 0.04). Maxima of sensitivity and specificity were observed at a threshold of 0.78 to define an abnormal PAT ratio. Cross-tabulation of groups above and below this threshold with groups of subjects with and without MSI showed a significant predictive relationship between PAT ratio and MSI (P = 0.03). Subjects at or below this threshold (¡Ü0.78) displayed a significant increase in norepinephrine levels during mental stress (235 pg/ml at baseline, 259 pg/ml during mental stress, P = 0.007). Subjects above this threshold (>0.78) displayed a significant decline in their ET-1 levels 24 hours after mental stress (1.15 pg/ml after mental stress, 0.93 pg/ml 24 hours later, P = 0.01), while those at or below threshold had a continued increase. PAT ratio is a complex functional measure of peripheral arterial tone that significantly predicts the occurrence of MSI. It may have clinical value as an easily administered screening test for MSI.

Flow-mediated dilation (FMD) is used as a surrogate marker for endothelial function, a subclinical indicator of coronary artery disease (CAD) and for that reason; FMD is commonly used to compare endothelial function across groups differing in age and number and/or type of CAD risk factors. The traditional calculation of FMD involves arterial diameter prior to cuff inflation and then peak arterial diameter following cuff release. Generally, arterial response during cuff inflation is not taken into consideration. The aims of the present study were to determine 1) if there were differences in brachial artery response, more specifically vasoconstriction, during cuff inflation in a diverse population of subjects, 2) if variability existed, the resulting impact on the calculation of traditional FMD, and 3) if arterial stiffness was a physiological determinant in this process. A total of 84 subjects, varying in age (18-62 years) and CAD risk factor profiles were studied. Low flow-mediated constriction (L-FMC), during cuff inflation, traditional FMD, and modified FMD, which accounts for L-FMC, were calculated to investigate brachial artery response during all three stages of the FMD measurement. Subjects ≥ 50 years old had lower FMD response compared with those ≤ 35 years old but only the modified FMD was statistically significant. The same effect was seen when comparing healthy subjects to those with multiple risk factors for CAD; there was an attenuated FMD response that only reached statistical significance with modified FMD. L-FMC was modestly but significantly associated with FMD. L-FMC was weakly but positively correlated with brachial pulse wave velocity (PWV). Our results indicate that modified FMD, which takes into consideration brachial response to cuff inflation, may be a more sensitive indicator of endothelial dysfunction and that arterial stiffening may be a physiological determinant in this process. / text

Coronary arteries are the blood vessels supplying oxygen-rich blood to the heart muscles. Coronary artery calcium (CAC), which is the total amount of calcium deposited in these arteries, indicates the presence or the future risk of coronary artery diseases. Quantification of CAC is done by using computed tomography (CT) scan which uses attenuation of x-ray by different tissues in the body to generate three-dimensional images. Calcium can be easily spotted in the CT images because of its higher opacity to x-ray compared to that of the surrounding tissue. However, the arteries cannot be identified easily in the CT images. Therefore, a second scan is done after injecting a patient with an x-ray opaque dye known as contrast material which makes different chambers of the heart and the coronary arteries visible in the CT scan. This procedure is known as computed tomography angiography (CTA) and is performed to assess the morphology of the arteries in order to rule out any blockage in the arteries. The CT scan done without the use of contrast material (non-contrast-enhanced CT) can be eliminated if the calcium can be quantified accurately from the CTA images. However, identification of calcium in CTA images is difficult because of the proximity of the calcium and the contrast material and their overlapping intensity range. In this dissertation first we compare the calcium quantification by using a state-of-the-art non-contrast-enhanced CT scan method to conventional methods suggesting optimal quantification parameters. Then we develop methods to accurately quantify calcium from the CTA images. The methods include novel algorithms for extracting centerline of an artery, calculating the threshold of calcium adaptively based on the intensity of contrast along the artery, calculating the amount of calcium in mixed intensity range, and segmenting the artery and the outer wall. The accuracy of the calcium quantification from CTA by using our methods is higher than the non-contrast-enhanced CT thus potentially eliminating the need of the non-contrast-enhanced CT scan. The implications are that the total time required for the CT scan procedure, and the patient's exposure to x-ray radiation are reduced.

No description available.

This thesis is a step forward in evaluating insulin therapy and defining its role in cardiac surgery first described as Glucose-Insulin-Potassium (GIK) solution 40 years ago. / Chapter (I) includes a review of the literature on insulin therapy in cardiac surgery and illustrates the scientific bases and controversies in this therapy. / Chapter (II) entitled: "Myocardial Protection During Elective Coronary Artery Bypass Grafting Using High Dose Insulin Therapy" represents a manuscript that was presented in the following meetings: (A) Local meetings: (1) McGill cardiovascular research day, February 1/2007, Montreal, Canada. (2) Fraser Gurd annual research day, McGill surgery department, May 31/2007, Montreal, Canada. (B) National meetings: (1) 11th Annual Terrence Donnelly research day for Canadian cardiac surgery residents, May 26/2007, Toronto, Canada. (C) International meetings: (1) 43rd Annual meeting of the Society of thoracic surgeons (STS), January 30/2007, San Diego, United States. A full manuscript was submitted to "The Annals of Thoracic Surgery" for review. / Chapter (III) entitled: "High Dose Insulin Therapy Attenuates Systemic Inflammatory Response in Patients Undergoing Elective Coronary Artery Bypass Grafting" represents a manuscript that was presented in the following meetings: (A) Local meetings: (1) Fraser Guard McGill Surgery department annual research day, May 3/2006, Montreal, Canada. (B) National meetings: (1) 10th Annual Terrence Donnelly research day for Canadian cardiac surgery residents, May 26/2007, Toronto, Canada. (2) Young investigator forum, Canadian Society of Clinical Investigators (CSCI), September 28/2006, Ottawa, Canada. (3) 59 th annual meeting of Canadian Cardiovascular Society (CCS), October 21/2006, Vancouver, Canada. (C) International meetings: (1) American Heart Association (AHA), November 12/2006, Chicago, United states. / Abstracts from this work were published in the following journals: (1) Clinical and Investigative Medicine, Vol. 29, No. 4, August 2006. (2) The Canadian Journal of Cardiology, Vol. 22 supp D, October 2006 (3) Circulation, Vol. 114 supp, No. 18, October 2006. / A full manuscript was submitted to "the journal of thoracic and cardiovascular surgery" for review.

Background: Cardiovascular disease (CVD) is becoming one of the leading causes of death in middle and low income countries, with ischaemic heart disease specifically being predicted to be the 4th and 5th causes respectively. The numerous risk factors for the development of CVD have been extensively researched; however, the same wealth of data is not available for the black South African population as there is for Caucasians. Although the same risk factors that are present in Caucasians have been seen to be present in the black South Africans, there are questions regarding the contributory roles of the individual risk factors, particularly within the context of urbanisation. The role of diet in CVD has been widely studied and it is known that with urbanisation there are dietary changes which are thought to add the development of CVD. With urbanisation, however, there are numerous other lifestyle changes taking place within a population, making it difficult to isolate and make conclusions of the individual role of diet. Added to this is the complex issue of assessing dietary intake. Assessing only nutrient or food intake does not give a holistic picture of dietary habits. The main aim of this study was to determine the association between dietary intake and CVD risk in black South Africans in the context of urbanisation. Methods: The first study that forms part of this thesis was a case-control study aimed at exploring the risk factor profile and clinical presentation of black South African patients with coronary artery disease (CAD). In this study clinical, biochemical and nutrient intakes were compared with a black South African control group that were matched for age and body composition. The second study to form part of this thesis aimed to relate the dietary intakes of the Prospective Urban and Rural Epidemiological (PURE) study population to CVD risk associated with urbanisation, by using both nutrient intake and predefined diet quality scores (DQS). The Healthy Diet Indicator (HDI) and the Deficiency and Excess Score were carefully selected from the large number of available scores and adapted as best as possible for the black South African population. The third study aimed to investigate the role of dietary intake by using nutrients as well as food group consumption patterns as a risk factor in urbanised black South African CAD patients. The dietary habits of the coronary artery disease (CAD) patients were compared to that of an apparently healthy reference group of volunteers selected from the PURE study population. This urbanised reference group was from a similar socio- demographic background and was selected according to their risk for CVD. The Reynolds Risk score which includes C-reactive protein as factor was used to stratify the PURE population into CVD risk categories, in order to select the reference group, which had a low risk (<5%) of developing CVD within the next 10 years. Dietary intake was assessed by comparing nutrient and food group intake (including the ultra-processed food group category). Results and discussion: Black South African CAD patients had increased levels of the same risk factors that are seen in Caucasians with insulin resistance and LDL size being particularly significant in their contribution. Apart from a lower vitamin C intake, no differences in dietary intake and physical activity were observed between the CAD and control group. When comparing the dietary intake of the rural and urban group, the urban group, who had an increased CVD risk, had higher intakes of macro- and micronutrients as well as higher DQS. The DQS must however be interpreted with caution, as when looking at the absolute intakes of individual components of the scores, the urban group was still deficient in a numerous vital micronutrients. A similar picture was seen in the third study, in that the CAD patients also consumed more saturated fatty acids and ultra-processed foods than the reference group, as well as more of the “protective” foods such as fruit and vegetables. However, although their dietary habits could be considered prudent, they were still inadequate in numerous important micronutrients. Conclusion and recommendation: This thesis therefore shows that there are two sides of the story regarding the role of diet in CVD in black South Africans. Although it is important to follow prudent dietary guidelines so as to control the intake of nutrients and foods known to play a role in the development of CVD, it is just as important to ensure adequate intake of the foods rich in micronutrients known to protect against CVD. Dietary advice and prevention programs should also focus on the adequacy aspect of the diet, such as increasing fruit and vegetable and low fat dairy intake, not only on the prudent diet aspect. Additionally, nutrient intake alone does not adequately explain the link between diet and CVD and additional analyses such food consumption patterns are required. / Thesis (PhD (Dietetics))--North-West University, Potchefstroom Campus, 2013

Background: Cardiovascular disease (CVD) is becoming one of the leading causes of death in middle and low income countries, with ischaemic heart disease specifically being predicted to be the 4th and 5th causes respectively. The numerous risk factors for the development of CVD have been extensively researched; however, the same wealth of data is not available for the black South African population as there is for Caucasians. Although the same risk factors that are present in Caucasians have been seen to be present in the black South Africans, there are questions regarding the contributory roles of the individual risk factors, particularly within the context of urbanisation. The role of diet in CVD has been widely studied and it is known that with urbanisation there are dietary changes which are thought to add the development of CVD. With urbanisation, however, there are numerous other lifestyle changes taking place within a population, making it difficult to isolate and make conclusions of the individual role of diet. Added to this is the complex issue of assessing dietary intake. Assessing only nutrient or food intake does not give a holistic picture of dietary habits. The main aim of this study was to determine the association between dietary intake and CVD risk in black South Africans in the context of urbanisation. Methods: The first study that forms part of this thesis was a case-control study aimed at exploring the risk factor profile and clinical presentation of black South African patients with coronary artery disease (CAD). In this study clinical, biochemical and nutrient intakes were compared with a black South African control group that were matched for age and body composition. The second study to form part of this thesis aimed to relate the dietary intakes of the Prospective Urban and Rural Epidemiological (PURE) study population to CVD risk associated with urbanisation, by using both nutrient intake and predefined diet quality scores (DQS). The Healthy Diet Indicator (HDI) and the Deficiency and Excess Score were carefully selected from the large number of available scores and adapted as best as possible for the black South African population. The third study aimed to investigate the role of dietary intake by using nutrients as well as food group consumption patterns as a risk factor in urbanised black South African CAD patients. The dietary habits of the coronary artery disease (CAD) patients were compared to that of an apparently healthy reference group of volunteers selected from the PURE study population. This urbanised reference group was from a similar socio- demographic background and was selected according to their risk for CVD. The Reynolds Risk score which includes C-reactive protein as factor was used to stratify the PURE population into CVD risk categories, in order to select the reference group, which had a low risk (<5%) of developing CVD within the next 10 years. Dietary intake was assessed by comparing nutrient and food group intake (including the ultra-processed food group category). Results and discussion: Black South African CAD patients had increased levels of the same risk factors that are seen in Caucasians with insulin resistance and LDL size being particularly significant in their contribution. Apart from a lower vitamin C intake, no differences in dietary intake and physical activity were observed between the CAD and control group. When comparing the dietary intake of the rural and urban group, the urban group, who had an increased CVD risk, had higher intakes of macro- and micronutrients as well as higher DQS. The DQS must however be interpreted with caution, as when looking at the absolute intakes of individual components of the scores, the urban group was still deficient in a numerous vital micronutrients. A similar picture was seen in the third study, in that the CAD patients also consumed more saturated fatty acids and ultra-processed foods than the reference group, as well as more of the “protective” foods such as fruit and vegetables. However, although their dietary habits could be considered prudent, they were still inadequate in numerous important micronutrients. Conclusion and recommendation: This thesis therefore shows that there are two sides of the story regarding the role of diet in CVD in black South Africans. Although it is important to follow prudent dietary guidelines so as to control the intake of nutrients and foods known to play a role in the development of CVD, it is just as important to ensure adequate intake of the foods rich in micronutrients known to protect against CVD. Dietary advice and prevention programs should also focus on the adequacy aspect of the diet, such as increasing fruit and vegetable and low fat dairy intake, not only on the prudent diet aspect. Additionally, nutrient intake alone does not adequately explain the link between diet and CVD and additional analyses such food consumption patterns are required. / Thesis (PhD (Dietetics))--North-West University, Potchefstroom Campus, 2013

Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.

Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.