From this series of studies, we conclude that microalbuminuria may represent a novel risk factor in SLE, and lupus patients are more susceptible to endothelial dysfunction caused by hyperhomocysteinemia. The use of antimalarial agents is beneficial for lupus patients with active disease on corticosteroid, and antioxidant vitamins are useful in lowering the oxidative stress markers but do not affect the endothelial function. The results highlight the importance of targeting the known modifiable risk factors in order to prevent premature atherosclerosis in SLE patients. / My first step was to elucidate the prevalence and metabolic abnormalities in SLE patients with microalbuminuria. Twenty percent of patients were found to have microalbuminuria, which was associated with higher mean arterial pressure, total plasma antioxidant and homocysteine levels. / Next, we recruited 12 SLE patients and 15 controls and gave them oral methionine loading to achieve acute hyperhomocysteinemia. After oral methionine loading, von Willebrand factor (vWF) levels increased significantly in both groups. The increase in vWF was apparently more pronounced in SLE (20%) compared to controls (8%). Fibrinogen binding to platelets increased significantly only in SLE patients. / Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of unknown cause which can affect any organs. Studies have reported an increased prevalence of cardiovascular disease (CVD) in these patients. We performed a series of studies to elucidate the interaction between microalbuminuria, dyslipidaemia, hyperhomocysteinemia, oxidative stress and immune dysregulation from the underlying disease in order to understand the accelerated atherosclerotic process in SLE. / We then evaluated the effects of long-term antioxidant vitamins. The plasma malondialdehyde level was significantly decreased after treatment in the vitamin group. Other oxidative stress markers and antioxidant levels and endothelial function remained unchanged in both groups. / We then proceeded to study the relative effect of antimalarial agents on fasting lipid fractions in patients with active SLE. Total cholesterol, very low-density lipoprotein cholesterol, and low density lipoprotein cholesterol levels were significantly lower in patients taking antimalarial agents, particularly for those patients taking concomitant prednisone. In the last study, we demonstrated that hydroxychloroquine had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease. / Tam Lai Shan. / Adviser: Edmund K. Li. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1550. / Thesis (M.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 178-214). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

As the prevalence of atherosclerosis has risen to an alarming level throughout the world, this thesis investigated: (1) the effects of type 2 diabetes mellitus on the risk factors for atherosclerosis and the intima-media thickness (IMT) of the common carotid arteries (a surrogate marker for atherosclerosis), (2) the contribution of various risk factors to the IMT of the common carotid arteries and (3) the interrelationship between the risk factors. / Atherosclerosis is the process by which the inner lining of a large or medium artery is deposited with lipids, cellular waste and other substances. It reduces the vessel's elasticity, lumen size and blood flow. Atherosclerosis is the primary underlying mechanism leading to cardiovascular and cerebrovascular diseases, the second and third leading causes of death in Hong Kong. / Both traditional and emerging risk factors for atherosclerosis were studied: traditional risk factors include age, blood pressure, indices of glycaemia control (fasting glucose, insulin and haemoglobin-Alc), and fasting lipids, while the emerging risk factors include, abdominal fat volume (subcutaneous and visceral), inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitivity c-reactive protein (hsCRP)), adiponectin, stress hormones (24 hr urinary noradrenaline and adrenaline, and plasma cortisol), and occupational stress (measured by a effort-reward imbalance questionnaire). / Starting with 204 subjects recruited from three different studies, data from 84 normoglycaemic subjects, 23 patients with impaired glucose tolerance (IGT) and 77 patients with diabetes mellitus (DM) were included in the analysis. When the IMT of the common carotid arteries and various risk factors were compared between normoglycaemic, IGT and DM subjects: (1) the IMT of the common carotid arteries showed an increasing trend with the worsening of glycaemia control (normal<IGT<DM), (2) increased prevalence of hypertension, dyslipidaemia, and obesity were observed among DM patients, and (3) increased levels of inflammatory markers, reduced concentration of adiponectin (a anti-inflammatory substance), and increased plasma cortisol concentration were also found among DM subjects. As the studies were limited by sample size, only a few risk factors were found significantly related to the carotid IMT. Age was the only common risk factor which was found to be correlated to the IMT of both the normoglycaemic and the DM/IGT subjects. (Abstract shortened by UMI.) / Fok Siu Pong. / "June 2005." / Adviser: Lester A. H. Critchley. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0173. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 200-228). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

[Truncated thesis] Background & Aims- The determinants of atherosclerosis in elderly postmenopausal women are poorly understood. We do not know if the traditional coronary heart disease (CHD) risk factors remain important in this group. Despite the growing body of data relating to exogenous estrogen, we know very little about the relationship of endogenous estrogen with inflammation, CHD risk factors and subclinical atherosclerosis in elderly women. Genes that may play a role in post-menopausal cardiovascular disease (CVD)(ER-α and Apo E gene polymorphisms) have not been examined in this population for their effect on sub-clinical atherosclerosis and whether this effect is modified by the level of endogenous estrogen. We have examined the effect of established cardiovascular risk factors, endogenous estrogen and Apo E genotype on carotid artery atherosclerosis in a large group of women over the age of 70 years. In smaller sub-groups, we have examined the relationship between ER-α gene polymorphisms and atherosclerosis and the relationship between endogenous estrogen and CRP. Methods- We studied 1149 ambulatory elderly women who were recruited from the electoral role in Perth, Western Australia in 1998 and subsequently underwent carotid ultrasound assessment in 2001 according to a standardised protocol (for detection of focal plaque and measurement of intimal-medial thickness). The subjects had a mean age of 75 years (range 70 to 82 years) at baseline. We assessed the following variables in almost all subjects at baseline; time from menopause, FEI (molar ratio of plasma estradiol to sex hormone binding globulin (SHBG) x 1000), systolic and diastolic blood pressure, total cholesterol, LDL and HDL cholesterol, triglycerides, body mass index, glycated haemoglobin, homocysteine, apolipoprotein E (ApoE) genotype, history of smoking, diabetes, cardiovascular disease and medication use. Four hundred and thirty three women were analysed for estrogen receptor alpha (ERα) genotype and 100 underwent measurement of high sensitivity C-reactive protein.

No description available.

Recent research has shown that the combination of high triglyceride (TG) levels and low high density lipoprotein (HDL) levels, significantly increases the incidence of coronary artery disease (CAD). The incidence of CAD is also increased in abdominally obese individuals. To assess differences in postprandial TG clearance patterns between abdominally obese (AO) and controls (C), fourteen healthy, normolipidemic males (seven controls and seven abdominally obese) completed an oral fat loading test (78 grams of fat). Blood samples were collected every hour for eight hours. Abdominally obese individuals had significantly greater TG values, significantly lower total HDL and HDL2 values and significantly greater area under the TG curve (p = 0.03). Time to reach peak TG and time to reach baseline TG values did not differ between the two groups, even though fewer AO individuals reached baseline within eight hours. The data from the present investigation indicate that increased time to clear TG in AO individuals may be one pathway that increases the incidence of CAD in this group. / School of Physical Education

[Truncated abstract. Please see the pdf format for the complete text.] The discovery of the C282Y mutation and its role in the development of hereditary haemochromatosis has allowed a greater understanding into the effects of iron overload and its involvement in other conditions such as diabetes and heart disease. It has also allowed the better classification of heterozygotes, who were previously only diagnosed through the use of family studies. There are however, areas of conflict between phenotyping and genotyping methods. My research involved examining the relationship between Haemochromatosis and certain diseases such as diabetes and heart disease; genotyping versus phenotyping discrepancies and the possible interaction of secondary mutations. In Chapter 3 a population study was undertaken with the aim of comparing genotyping versus phenotyping methods as well as increasing general practitioner awareness regarding hereditary haemochromatosis and its diagnosis. It was determined that a minimum of 5000 subjects would be required to give the study sufficient power. Individuals were to be between the ages of 20—40 years, and thus presumably presymptomatic. Participation was entirely voluntary and a consent form was to be signed. Recruitment of subjects proved to be difficult and there was a selective bias towards individuals already displaying symptoms of haemochromatosis. In total less than a 100 subjects were recruited for the study. There were several issues encountered in the implementation of this study. Firstly the number of GPs participating was probably insufficient to recruit the subjects required. A more extensive campaign was probably required to enroll more GPs. Secondly it is very difficult for a busy GP to find the time necessary to explain the study to each of his patients and to get them to sign the consent form. Finally a bias developed in some of the requests. The subjects participating in this study were supposed to be random but in many cases the GPs had enrolled them in the study because they had symptoms of iron overload. In effect the biggest obstacle this study faced was the recruitment of subjects. Due to the small number of subjects little statistical data could be obtained from this study. It was noted, however, that genotyping methods detected two individuals who were homozygous for the C282Y mutation. Both also had increased transferrin saturation levels. Phenotyping detected 5 individuals with increased transferrin saturation. The three others detected via phenotyping were C282Y heterozygotes. Haemochromatosis has long been though to be related to the development of diabetes due to the effect of iron overload on the pancreas. If this is so it would be logical to assume that the prevalence of haemochromatosis would be higher in a diabetic population. Chapter 4 examined the possibility that diabetics have a higher frequency of the C282Y mutation. A population group consisting of 1355 diabetics was genotyped for the C282Y mutation and iron studies were performed on all heterozygotes and C282Y homozygotes. Initial findings indicated that there was a significant difference between the diabetic and control population. However, this finding was the opposite of what was expected, there seemed to be a decreased frequency of the Y allele in the diabetic population rather than an increased one. The control and diabetic populations were not matched in terms of ethnicity. The removal of the ethnic bias in the diabetic population altered the statistics so there was no longer a significant difference between the two groups. This study highlighted the importance of using appropriate control populations as comparison groups. The final results of the study indicated that there was no significant difference between the diabetic population and the control population. This would seem to indicate that there is not an increased occurrence of the C282Y mutation in the diabetic population when compared to the control group. Chapter 5 considered the possible association between C282Y heterozygosity and cardiovascular disease as well as the potential for early mortality. Several recent studies have indicated that C282Y heterozygosity may be a risk factor for the development of atherosclerosis, possibly on the basis of increased iron loading. Using a control population and a population of individuals with known coronary events the incidence of the C282Y mutation was compared against other risk factors. C282Y heterozygosity did not appear to be a risk factor for atherosclerosis. There was however, a statistically significant link between increased ferritin in women and carotid plaques. A population of elderly women was genotyped in order to examine the effects of C282Y heterozygosity on longevity. The first hypothesis addressed in chapter 5 was that C282Y heterozygosity was a risk factor for the development of coronary heart disease.

Cardiovascular diseases (CVD) have been one of the leading causes of morbidity and mortality in developed countries with an enormous influence on individual health and significant socioeconomic impact as well. The aim of most physicians in recent decades is to seek the best possible predicative risk factor (RF) (or combination of several RF) which could help to determine the individual risk of developing CVD. This risk stratification can be used to identify the high risk patients and treatment intensification or establishment of early preventive measures. Currently, several RF of atherosclerosis and CVD are commonly used to individualize health care. However, individuals with low levels of these RF suffer of CVD, therefore the effort to find as much as possible specific RF still persists. In recent years, the inflammatory markers, crucial in the atherosclerosis development, raise great expectation In our studies, we focused on investigating the levels of inflammatory parameters in specific groups of patients (obese children and patients with metabolic syndrome) and observed the effect of weight loss following lifestyle changes. Our main concern was lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized LDL particles (ox-LDL) and myeloperoxidase (MPO). The results demonstrated significantly...

Background and objective. Ultrasonic evaluation of carotid intima media thickness (IMT) has been widely used as a surrogate of atherosclerosis. Few studies have specifically examined risk factors related to subclinical atherosclerosis (SA) among early postmenopausal women, in particular in the Chinese population. There is also little information on the distribution of IMT in Asian midlife women. We described the prevalence of SA, as determined by IMT and carotid plaque, and the associated risk factors in early postmenopausal Chinese women in Hong Kong. / Conclusions. Our findings showed that age, SBP, HDL-C, and LDL-C were independent predictors of IMT, while age, LDL-C, and abdominal obesity were independent predictors of the presence of plaque. The optimal IMT cutoff of 0.783 mm was defined and that a prevalence of SA (IMT ≥ 0.783 mm) of 38.6% was found among 'healthy' early postmenopausal Chinese women in Hong Kong. / Methods. 518 women aged 50 to 64 years, and within 10 years since menopause were recruited from random telephone dialing. Women with surgical menopause, established cardiovascular diseases (CVD), and severe disease conditions such as cancer and renal failure were excluded. Sociodemographic, anthropometric and lifestyle factors were obtained based on standardized questionnaires. Fasting blood sample was also obtained. B-mode ultrasound was used for measuring IMT at 12 sites of the carotid arteries and plague index, which is the sum of the grades (ranged from 0 to 3) at the 6 segments. The relations between traditional risk factors, and other potential risk factors such as inflammatory markers, as well as lifestyle factors including physical activity, dietary intake, and psychological factors with SA were also assessed. / Results. The mean IMT +/- SD was 0.76 +/- 0.12 mm, with a range from 0.53 to 1.00 mm. IMT was higher on the far wall than on the near wall (P<0.01), and differ among segments (greatest at the bulb and least at the ICA) (P<0.01). One-fifth of women had at least 1 plaque in the carotid artery with most of the plaque occurred in the bulb area. IMT increased with age, and was positively associated with carotid plaque. With the use of receiver operating characteristic curve (ROC) analysis, the optimal cutoff IMT for diagnostic plaque was 0.783 mm, at which sensitivity and specificity was 80.5% and 75.1%, respectively. The prevalence of SA was 38.6%. Among the traditional risk factors, systolic blood pressure (SBP), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were associated with high IMT. Abdominal obesity assessed by waist circumference (WC) and waist hip ratio (WHR) was also found to be positively associated with IMT. Stepwise multiple regression showed that age, SBP, HDL-C, and LDL-C were independent predictors of IMT. Multiple logistic regression showed that women with LDL-C ≥ 130 mg/dL were associated with a 2.4-fold (95% CI 1.5-3.7) higher risk of having plaque compared to those with LDL-C < 130 mg/dL. In addition, women with abdominal obesity (WHR ≥ 0.85) had a 1.7-fold (95% CI 1.08-2.67) higher risk of having plaque than women with WHR < 0.85 after adjustment for age, and potential confounders including physical activity, dietary intakes etc. Significant inverse associations were observed between physical activity and indices of obesity, as well as fasting blood glucose, while psychological perceived stress and trait anxiety were independent risk factors for both total cholesterol and LDL-C. / Yu Ho-yan. / "February 2006." / Adviser: Suzanne C. Ho. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6350. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 220-256). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

published_or_final_version / Community Medicine / Master / Master of Philosophy

Childhood obesity is currently considered a serious pediatric problem. The main risk of this metabolic disease lies in the shift of comorbidities associated with obesity to ever younger age categories. This is also related to the increasing overall cardiometabolic risk in these obese individuals. Early detection and treatment of childhood obesity is an essential task of pediatrics. The possibility of non-pharmacological treatment of childhood obesity is spa treatment. It consists of intensive reduction therapy, which includes nutritional, physical and educational interventions. The aim of the study was to monitor changes in anthropometric and biochemical parameters after monthly treatment in pediatric patients. Furthermore, to identify and specify selected potential markers of cardiometabolic risk that significantly correlate with BMI and could be useful in children and adolescents. The thesis also focused in detail on two adipocyte hormones - leptin and adiponectin, which already correlate with the amount of adipose tissue in the pediatric population. These hormones could become significant predictive parameters of metabolic syndrome, subclinical atherosclerosis and other comorbidities associated with obesity and cardiovascular risk, already in children. Based on our measurements we can confirm...