Study methods: Mixed-method study design was used to investigate feasibility of implementing a mobile-phone based behavioural intervention to reduce CVD risk factors among the Chinese population. Patients, who were 45-79 years old, fair English literacy, had access to a JAVA enabled mobile phone and had no mental health problems, cognitive impairment or severe illness, were eligible to the study. Intervention: Patients recruited from three settings (1 GP, 1 specialist and 1 public clinics) had the study software installed to their phone. The software enabled patients to access their CVD risk profiles (including weight, BP, HbA1c, and lipoprotein profile), 10-year CVD risk prediction (based on Framingham Cardiac Risk Score), and pre-set behavioural recommendations. Patients’ CVD risk profiles were updated at 1-month and 3-month follow-up when their test results were available. Patients were alerted with healthy behaviours recommendations. Outcomes: Outcomes were measured at baseline and 3-month follow-up. Clinical outcomes included Cardiac Risk Factor Score and its components (BMI, Systolic & Diastolic BP, total cholesterol, HDL and HbA1c). Two sets of questionnaires were used to measure knowledge, risk reduction behaviour and attitude toward usefulness of medical records (pre-intervention) and perceived ease of use, usefulness, satisfaction and utilisation of the software (post-intervention). Results and Discussion: 19 patients were recruited at baseline. 75% (14) aged 45-55 years, 58% (11) were male, 79% (15) had secondary or lower education, 63% (12) were married, and 95% (18) never smoked. Patients’ understanding about CVD risk factors and risk reduction behaviour was moderate. Patients’ attitude toward electronic medical record was positive. Overall patients’ perception of usefulness, ease of use and satisfaction with the software was satisfactory. Post-intervention, a decreasing trend was observed in patients’ CVD risk profiles i.e. weight, BMI, SBP&DBP, HbA1c and Lipoprotein profile. Focus group discussions revealed that there was a mismatch between physicians and patients perspectives about the use of mobile phone in a behavioural intervention. Physicians tended to express their concern about the quality of records, security of technology, and patients’ actual benefit, while patients showed little concern about security and great excitement about further use of mobile phone technology in assisting their disease self-management. The public sector physicians admitted that their patients were passive in term of seeking information about their health. Patients were willing to use this software for future care if it could provide more real-time data, tailored recommendations for behavioural change, and an interactive communication tool with their physicians. Physicians would like to try the software if it could ease patient-management process, especially enhance patient-physician communication, and be a decision support system to help them keep track with changes that their patients made. Conclusion: This pilot study has provided preliminary evidence of the feasibility, acceptability, and utility of an e-platform in primary interventions for CVD in Hong Kong. / published_or_final_version / Community Medicine / Master / Master of Philosophy

Background: Chronic Obstructive Pulmonary Disease (COPD) poses a substantial burden to Hong Kong. Smoking is the single most important risk factor for COPD. Intensive smoking cessation in COPD patients slows disease progression. Community pharmacy based smoking cessation in healthy smokers could forestall COPD onset. Each of these programs has been proven effective and cost-effective worldwide. Currently there are smoking cessation clinics in Hong Kong. But community pharmacy-based smoking cessation services are not available. The present study firstly attempts to identify the disease burden of COPD; secondly, to investigate if community pharmacy-based smoking cessation services are applicable in Hong Kong; finally, to examine if establishing the services would be cost effective in reducing the burden of COPD. Methods: A series of data analysis of mortality, morbidity and cost of hospitalization (length of stay × standard daily ward cost) was conducted to understand the burden of COPD in Hong Kong. Cost effectiveness analysis based on a Markov model evaluated smoking cessation strategies against usual care: (1) minimal counseling in smoking cessation clinics (MiniC) for COPD patients; (2) intensive counseling with pharmacotherapy in smoking cessation clinics (IC_pharm) for COPD patients; (3) community pharmacist-assisted service (CPA) for healthy smokers; (4) combination of CPA and MiniC (CPA+MiniC); (5) combination of CPA and IC_pharm (CPA+IC_Pharm). The Markov model was constructed by sex, smoking status and COPD severity to calculate the lifetime cost of COPD, cost of smoking cessation programs and QALYs. Both effectiveness and cost were discounted at 3%. Incremental cost effectiveness ratios (ICERs), i.e. cost per one QALY gain, served as the decision making rule. One way sensitivity analysis, threshold analysis and probabilistic sensitivity analysis were performed to explore the uncertainty around the parameters. Results: The overall age adjusted mortality of COPD increased from 28.8 per 100 000 in 1981 to 30.14 per 100 000 in 2008. Numbers of people aged 65+ with known COPD was projected to be over 100 000 by 2036. There were 3.8 and 7.8 years of life lost (YLL) and 3.6 and 5.6 QALYs lost due to COPD for male and female smokers respectively. Medical costs of hospitalization were estimated to be over HK$ one billion (US$132 million) in 2008. Seventy one COPD cases could be avoided in the simulated cohort by CPA. If the threshold value was HK$247 332 for one QALY gain, CPA was more cost effective than IC_Pharm, with an ICER of HK$47 717. CPA+MiniC dominated CPA. CPA+IC_Pharm was more cost effective than CPA+MiniC (ICER, HK$36 000). The probability of CPA+ IC_pharm being the most cost effective strategy was approaching 0.8 if one QALY was worth HK$96 000, and it was associated with the maximum expected QALYs if societal value for one QALY was no less than HK$80 000. Conclusion: The model-based economic evaluation demonstrated that CPA+IC_Pharm would be the most cost-effective smoking cessation strategy. Community pharmacy based (CPA) smoking cessation services could be applicable and should be proposed in Hong Kong to reduce the burden of smoking related diseases. / published_or_final_version / Public Health / Doctoral / Doctor of Philosophy

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Traditional indicators of cardiovascular disease (CVD) risk may not be appropriate for Asian Indians. We designed a cross-sectional study of body fat distribution, apoB/apoA1 ratio and adipokines of Northern Indians compared to Caucasians to determine if there is a different relationship between these parameters. Indian (men: n = 54; women n = 28) and Caucasian (men: n= 32; women, n = 51) subjects were recruited who were between the ages of 20 and 60 years. Subjects were excluded if they had a history of CVD or were taking lipid lowering medications. Body fat percentage (BF%) was measured using bioelectrical impedance analysis. Indian subjects had a substantially higher waist-to-hip ratio (WHR) ratio than Caucasian subjects (men: 0.93 +/- 0.01 vs. 0.86 +/- 0.01, p < 0.001; women: 0.88 +/- 0.01 vs. 0.76 +/- 0.01, p < 0.0001). Interestingly, while WHR correlated strongly with BF% in Caucasians (men: r = 0.63 p = 0.0002; women: r = 0.74, p < 0.0001, respectively) there was no correlation in Indians (men: r = 0.22, ns; women: r = 0.23, ns). The regression lines for WHR vs. BF% of Indians compared to Caucasians was significantly different (men p = 0.02, women p = 0.002). A similar pattern of correlation was seen with WHR and BMI. In addition, Indian men and women had a higher apoB/A1 ratio than Caucasians: the most powerful lipoprotein measure of CVD risk (men: 0.84+/-0.04 vs. 0.66+/-0.04, p=0.001; women: 0.70+/-0.04 vs. 0.56+/-0.03, p = 0.003, respectively). Leptin levels were higher and adiponectin levels in lower in the Indian men and women. Hypothetically, these alterations in body composition, apoB/apoA1 and adipokines could be due to alterations in adipocyte number.

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Nutritional and/or genetic disruptions in homocysteine metabolism can cause hyperhomocysteinemia. Mild methylenetetrahydrofolate reductase (MTHFR) deficiency due to the 677C → T mutation in the MTHFR gene is the most common genetic cause of hyperhomocysteinemia. The 677C → T variant is associated with an increased risk for neural tube defects, pregnancy complications, schizophrenia and Down syndrome, and with a decreased risk for colon cancer and leukemia. This variant is also a potential risk factor for vascular disease. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. We have generated mice with a knockout of the Mthfr gene. The Mthfr-deficient mice exhibit hyperhomocysteinemia and decreased methylation capacity. The Mthfr+/- mice appear normal, whereas the Mthfr-/- mice are smaller and have reduced survival. Abnormal external granule neuron development associated with increased cell death in the cerebellum was observed in the Mthfr-/- mice. / Evidence for cardiovascular pathology was obtained in several ways. Impaired aortic relaxation response to acetylcholine was seen in the Mthfr +/- mice fed a high methionine diet. Both Mthfr+/- and Mthfr-/- mice fed a low folate high methionine diet developed myocardial fibrosis in the left ventricle. Abnormal lipid deposition in the proximal portion of the aorta was observed in older Mthfr+/- and Mthfr-/- mice. After crossing Mthfr -deficient mice with apoE-null mice, we demonstrated that MTHFR deficiency promoted atherogenesis and its progression in the apoE-null mice. / Gene expression in brain of Mthfr-deficient mice was investigated via microarray analysis. Five genes with altered expression in the brain of Mthfr-/- mouse were validated by RT-PCR. In biochemical studies of human MTHFR, both FAD and folate were shown to stabilize the purified recombinant wild type and mutant MTHFRs from the baculovirus expression system against heat inactivation. The effect of folate appeared to be secondary to that of FAD, and S-adenosylmethionine (SAM) inhibited purified wild type and mutant MTHFRs with similar efficiency. / This dissertation will significantly contribute to our understanding of the role of MTHFR in human disease.

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / Department of Physiology and Health Science

Purpose: Cardiac rehabilitation (CR) programs have been shown to promote numerous health benefits among patients with cardiovascular disease (CVD), but little is known about the characteristics of CR programs. Methods: A survey was developed and utilized to collect data on Early Outpatient Cardiac Rehabilitation programs (EOCR) in the USA. An email with a link to the survey was sent by the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) to their members. Program directors/administrators were recruited to provide information about their program in operation during 2009 in the United States. The CR survey contained 13 questions, some with multiple answers, regarding the utilization and patient demographics of an Early Outpatient Cardiac Rehabilitation (Phase II) program. Results: Responses were received from 138 programs in 44 states. Of the responses, 19,689 patients completed at least one EOCR exercise session. Of the responses, 68% of patients were men and 32% of patients were women. Patients enrolled in EOCR programs had a primary diagnosis of CABG 4,803 (30%); AVR/MVR 1,401(9%); MI 3,583 (22%); PCI/Stent 4,961 (31%); stable angina 965 (6%); heart/lung transplant 53 (0.33%); other 385 (2%). 8.4% complete 0-6 sessions of EOCR; 12% complete 7-12 sessions; 22% complete 13-18 sessions; and 58% complete 19-36 sessions. 35% of patients enrolled in EOCR programs are discharged early. 84% of programs offer an outpatient maintenance CR program. 96% of EOCR programs offer education classes; 89% offer resistance equipment; 72% are AACVPR certified; 62% also offer pulmonary rehabilitation; 23% utilize outcome measurements; 62% are in rural locations; and the average patient-to-staff ratio is 4.2:1. Conclusions: CR programs are used by a minority of eligible patients. There is marked variation in the structure and content of EOCR programs. Alternative strategies to improve standardization and outcomes should be implemented. / School of Physical Education, Sport, and Exercise Science

Autoantibodies generated against M proteins can cause post-streptococcal disorders such as Rheumatic Fever. A severe complication of rheumatic fever is rheumatic heart disease which may involve both cardiomyopathy and valvulitis. Rheumatic fever has been associated with the class I M protein epitope of Group A streptococcus (GAS). This epitope can be recognized by monoclonal antibodies (mAbs) 10B6 and 10F5. Previously, we demonstrated binding of streptococcal mAb10F5 in the heart tissue (apex, atria, and valves) of Lewis rats as compared to anti-myosin binding. To determine if mAb10F5 binding in the heart is due to virulence of the antibody or antibody subtype, rats were injected with control IgG2 antibodies and euthanized after 24, 48, or 72 hrs. Hearts were harvested and immunofluorescence was used to analyze the hearts. The immunofluorescence intensities for IgG2b were compared to mAb10F5 using previously acquired data. Control IgG2b rats showed significantly less immunofluorescence intensities in the heart regions than mAb10F5 injected rats at the 48 and 72 hr time points. These findings reaffirm mAb10F5 as an anti-cardiac antibody thatbinds heart tissue due its own virulence. To differentiate between the two IgG subtypes, binding intensities of IgG2a were compared to the binding intensities of IgG2b. The binding intensities of IgG2a increased with time. This finding was supported by previous work in our laboratory suggesting IgG2a remained in the bloodstream longer than the IgG2b. / Access to thesis permanently restricted to Ball State community only. / Department of Physiology and Health Science