Contribution of changes in risk factors to the decline of coronary heart disease mortality in Australia over three decades

BACKGROUND: Coronary heart disease has been a major cause of mortality in Australian adults, but the rate has declined by 83% from the 1968 peak by the year 2000. The study objective is to determine the contribution of changes in population risk factors - mean serum cholesterol and diastolic blood pressure and tobacco smoking prevalence - to the decline in coronary heart disease mortality in Australia over three decades. METHODS: Coronary heart disease deaths (International Classification of Disease-9, 410-414) and population by year, age group and sex were obtained from the Australian Bureau of Statistics. Risk factor levels were obtained from population surveys and estimated average annual changes by period were used to calculate average annual 'attributable' proportional declines in CHD mortality by period (age 35-64 years). RESULTS: Over the period 1968-2000, 74% of male decline and 81% of the female decline in coronary heart disease mortality rate was accounted for by the combined effect of reductions in the three risk factors. In males 36% of the decline was contributed by reductions in diastolic blood pressure, 22% by cholesterol and 16% by smoking. For females 56% was from diastolic blood pressure reduction, 20% from cholesterol and 5% from smoking. Effects of reductions in serum cholesterol on coronary heart disease mortality occurred mainly in the 1970s. Declines in diastolic blood pressure had effects on coronary heart disease mortality over the three decades, and declines in tobacco smoking had a significant effect in males in the 1980s. CONCLUSION: Most of the spectacular decline in coronary heart disease mortality over the last three decades in Australia can be ascribed to reductions in population risk factors from primary and secondary prevention.

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial

Background The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. Methods In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. Findings 1383 participants underwent full shin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new shin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100 000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100 000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100 000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100 000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100 000; 0.61 [0.46-0.81]). Interpretation There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Ocular and systemic markers for vascular function in those at risk of type 2 diabetes mellitus and cardiovascular disease

The devastating impact of Type 2 Diabetes Mellitus (T2DM) -related morbidity and mortality on global healthcare is escalating with higher prevalences of obesity, poor diet, and sedentary lifestyles. Therefore, the clinical need for early diagnosis and prevention in groups of high-risk individuals is necessary. The purpose of this thesis was to investigate the use of surrogate markers, namely retinal vascular function, to determine future vascular endothelial dysfunction, atherosclerosis, large vessel disease and cardiovascular risk in certain groups. This namely covered normoglycaemic and normotensive South Asians (SAs), those with Impaired-Glucose Tolerance (IGT) and individuals with a familial history (FH) of T2DM. Additionally the effect of overweight and obesity was studied. The techniques and modified protocols adopted for this thesis involved the investigation of endothelial function by means of vascular reactivity at the ocular and systemic level. Furthermore, the relationships between retinal and systemic function with circulating markers for endothelial cell function and cardiovascular risk markers were explored. The principal studies and findings of the research were: Vascular Function in Normoglycaemic Individuals with and without a FH of T2DM WE FH individuals exhibited higher levels of total cholesterol levels that correlated well with the retinal arterial dilation amplitude to flicker light stimulus. However this did not extend to noticeable differences in markers for endothelial cell damage and impaired retinal and systemic function. Vascular Function in Normoglycaemic South-Asians vs. White-Europeans without a FH and Vascular Disturbances Compared to healthy WEs (normo -glycaemic and -tensive), SA participants exhibited levels of dyslipidaemia and a state of oxidative stress that extended to impaired vascular function as detected by reduced brachial artery flow-mediated dilation, slower retinal arterial vessel dilation reaction times (Appendix 3) and steeper constriction profiles. Furthermore, gender sub-group analysis presented in a sub-chapter shows that SA males demonstrated 24-hour systemic blood pressure (BP) and heart rate variability (HRV) abnormalities and heightened cardiovascular disease (CVD) risk. Vascular Function in Individuals Newly Diagnosed with IGT as compared to Normoglycaemic Healthy Controls Newly-diagnosed WE and SA IGT patients showed a greater risk for CVD and T2DM progression by means of 24-hour BP abnormalities, dyslipidaemia, increased carotid artery intimal-media thickness (c-IMT), Framingham scores and cholesterol ratios. Additionally, pre-clinical markers for oxidative stress and endothelial dysfunction, as evident by significantly lower levels of plasma glutathione and increased levels of von-Willebrand factor in IGT individuals, extended to impaired vascular systemic and retinal function compared to normal controls. This originally shows retinal, systemic and biochemical disturbances in newly-diagnosed IGT not previously reported before. Vascular Function in Normal, Overweight and Obese Individuals of SA and WE Ethnicity In addition to the intended study chapters, the thesis also investigated the influence of obesity and overweight on vascular function. Most importantly, it was found for the first time that compared to lean individuals it was overweight and not obese individuals that exhibited signs of vascular systemic and ocular dysfunction that was evident alongside markers of atherosclerosis, CVD risk and endothelial damage.

The effect of genetically-mediated taste acuity for 6-N-propylthiouracil (PROP) on food choice and diet-related disease

Taste acuity for the bitter taste of 6-n-propylthiouracil (PROP) is a heritable trait. Some individuals perceive concentrated levels of PROP to taste extremely bitter (supertasters) or moderately bitter (medium tasters), whereas others detect only a mild taste or none at all (non-tasters). Heightened PROP acuity has been reported to be associated with greater acuity for a variety of compounds found in ordinary foods, although there are some inconsistent findings. The extent to which these compounds are perceived may affect food likes/dislikes and dietary intake. The majority of studies have tended to measure food likes and intake using questionnaires or laboratory preparations of a single taste quality. The present study used food diaries and sensory responses to real foods to be better able to generalise to real eating situations. There was no substantial evidence that genetically mediated taste acuity for PROP had a direct influence on food likes/dislikes or intake, although there was evidence that dietary restraint could have influenced these findings among the female samples. However; investigation of PROP tasting among individuals with coronary heart disease (CHD) and a control group suggested that PROP acuity could function as a genetic taste marker for heart disease and potentially other diet-related conditions. CHD was associated with decreased PROP acuity among men. This is consistent with the findings that decreased PROP acuity tended to be associated with increased likelihood to be a smoker and higher body mass index. It is concluded that there is not a simple and direct relationship between PROP tasting ability and food choice. An interaction between PROP acuity and other mediating factors may be involved in a more complex model of food choice. The evidence that PROP taste acuity may function as a genetic taste marker for coronary heart disease could have wide implications for understanding the aetiology, and ultimately the prevention, of diet-related disease.

The effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease

There is interest in the use of nutritional supplementation as a prevention and treatment strategy for age-related macular disease as later stages of the condition are the leading cause of visual disability in the developed World .

Monocytes in coronary artery disease and atherosclerosis:where are we now?

Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function.

Illness perceptions, beliefs and prevention of Type 2 Diabetes among British Pakistani mothers and young British Pakistani women

The prevalence rates of type2 diabetes mellitus (T2DM) continues to rise among British Pakistanis. The aim of this project was to explore T2DM perceptions and any preventative intentions among British Pakistani women and to discover whether they are doing anything to prevent the onset in themselves and their families. Initially a systematic review was conducted to investigate 20 existing prevention interventions and to assess their effectiveness (n=12,419). Mixed methods approach was adopted and three studies were conducted. The first study consisted of two focus groups with T2DM mothers (n=8) and three focus groups with non-T2DM mothers (n=17). The second study consisted of four focus groups young British Pakistani females (n=11). All focus groups were transcribed verbatim and analysed using thematic analysis. Following these a quantitative study was undertaken comprising of a questionnaire survey; 12 prevention-perception items (derived from the qualitative data) and the Illness-Perception Questionnaire Revised (IPQ-R) using participants from the same populations: T2DM mothers (n=41), non-T2DM mother (n=47) and young women (n=42). Results were analysed using multiple/hierarchical regression. The systematic review highlighted that the most effective prevention programmes focussed on behaviour and lifestyle with a combination of support and education to participants. The research studies demonstrated that T2DM was seen as an older person’s disease to be dealt with if/when it happens. T2DM mothers demonstrated knowledge and prevention understanding. There were non-significant relationships between prevention perceptions and T2DM illness perceptions across all three groups. The finding of this thesis emphasised that lifestyle interventions are crucial to aiding T2DM preventions as a good healthy diet and regular physical activity are the key components to T2DM prevention, and the importance of personal experience in perceived severity and lay-beliefs regarding T2DM and on family/cultural influences in British-Pakistanis. The findings of this project can be used to design culturally specific interventions towards preventing T2DM in the British Pakistani community.

A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes:design and methodology [ISRCTN78467674]

Background: Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. Methods: The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. Discussion: A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition.

Vaginal microbicides for the prevention of HIV transmission

The human immunodeficiency virus (HIV) kills more people worldwide than any other infectious disease. Approximately 42 million people, mostly in Africa and Asia, are currently infected with HIV (Figure 3.1), and 5 million new infections occur every year (AIDS Epidemic Update, 2002). It is estimated that 22 milIion people have died since the first clinical evidence of AIDS (acquired immunodeficiency syndrome) emerged in 1981 ('Mobilization for Microbicides' ~ The Rockfeller Foundation). HIV is generally transmitted in one of three ways: through unprotected sexual intercourse, blood-to-blood contact, and mother-to-child transmission. Once the virus has entered the body, it invades the cells of the immune system and initiates the production of new virus particles with concomitant destruction of the immune cells. As the number of immune cells in the body slowly declines, weight loss, debilitation, and eventually death occur due to opportunistic infections or cancers. Although AIDS is presently incurable, highly active antiretroviral therapy (HAART), where a cocktail of potent antiretroviral drugs are administered daily to HIV-positive patients to control the viral load, has resulted in dramatic reductions in HIV-related morbidity and mortality in the developed world

Lack of effect of aspirin in primary CV prevention in type 2 diabetic patients with nephropathy:results from 8 years follow-up of NID-2 study

The risk-to-benefit ratio for the use of low dose of aspirin in primary cardiovascular (CV) prevention in patients with diabetes mellitus remains to be clarified. We assessed the effect of aspirin on risk of CV events in type 2 diabetic patients with nephropathy, in order to verify the usefulness of Guidelines in clinical practice. We carried out a prospective multicentric study in 564 patients with type 2 diabetic nephropathy free of CV disease attending outpatient diabetes clinics. A total of 242 patients received antiplatelet treatment with aspirin 100 mg/day (group A), and 322 were not treated with antiplatelet drugs (group B). Primary end point was the occurrence of total major adverse cardio-vascular events (MACE). Secondary end points were the relative occurrence of fatal MACE. The average follow-up was 8 years. Total MACE occurred in 49 patients from group A and in 52 patients from group B. Fatal MACE occurred in 22 patients from group A and in 20 from group B; nonfatal MACE occurred in 27 patients from group A and in 32 patients from group B. Kaplan-Meier analysis did not show a statistically significant difference of cumulative MACE between the two groups. A not statistically significant difference in the incidence of both fatal (p = 0.225) and nonfatal CV events (p = 0.573) between the two groups was observed. These results were confirmed after adjustment for confounders (HR for MACE 1.11, 95 % CI 0.91-1.35). These findings suggest that low dose of aspirin is ineffective in primary prevention for patients with nephropathy. © 2014 Springer-Verlag Italia.

Explaining the increase in coronary heart disease mortality in Syria between 1996 and 2006

Background Despite advances made in treating coronary heart disease (CHD), mortality due to CHD in Syria has been increasing for the past two decades. This study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to investigate the main factors associated with them. Methods The IMPACT model was used to analyze CHD mortality trends in Syria based on numbers of CHD patients, utilization of specific treatments, trends in major cardiovascular risk factors in apparently healthy persons and CHD patients. Data sources for the IMPACT model included official statistics, published and unpublished surveys, data from neighboring countries, expert opinions, and randomized trials and meta-analyses. Results Between 1996 and 2006, CHD mortality rate in Syria increased by 64%, which translates into 6370 excess CHD deaths in 2006 as compared to the number expected had the 1996 baseline rate held constant. Using the IMPACT model, it was estimated that increases in cardiovascular risk factors could explain approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented or postponed by medical and surgical treatments for CHD. Conclusion Most of the recent increase in CHD mortality in Syria is attributable to increases in major cardiovascular risk factors. Treatments for CHD were able to prevent about a quarter of excess CHD deaths, despite suboptimal implementation. These findings stress the importance of population-based primary prevention strategies targeting major risk factors for CHD, as well as policies aimed at improving access and adherence to modern treatments of CHD.

A Systematic Review of Internet-Based Worksite Wellness Approaches for Cardiovascular Disease Risk Management: Outcomes, Challenges & Opportunities

Context The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV) wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. Evidence Acquisition We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA) indicators of cardiovascular wellbeing – weight, BP, lipids, smoking, physical activity, diet, and blood glucose. Evidence Synthesis A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6 – 24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. Conclusion Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

Obesity, cardiovascular disease risk factors and weight loss in a population of adult Mexican Americans

The study of obesity has evolved into one of the most important public health issues in the United States (U.S.), particularly in Hispanic populations. Mexican Americans, the largest Hispanic ethnic subgroup in the U.S., have been significantly impacted by obesity and related cardiovascular diseases. Mexican Americans living in the Lower Rio Grande Valley (the Valley) in the Texas-Mexico border are one of the most disadvantaged and hard-to-reach minority groups. Demographic factors, socioeconomic status, acculturation, and physical activity behavior have been found to be important predictors of health, although research findings are mixed when establishing predictors of obesity in this population. Furthermore, while obesity has long been linked to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and dyslipidemia; information on the relationships between obesity and these CVD risk factors have been mostly from non-minority population groups. Overall, research has been mixed in establishing the association between obesity and related CVD risk factors in this population calling attention to the need for further research. Nevertheless, identifying predictors of success for weight loss in this population will be important if health disparities are to be addressed. The overall objective of the findings presented in this dissertation was to attain a more informed profile of obesity and CVD risk factors in this population. In particular, we examined predictors of obesity, measures of obesity and association with cardiovascular disease risk factors in a sample of 975 Mexican Americans participating in a health promotion program in the Valley region. Findings suggest acculturation factors to be one of the most important predictors of obesity in this population. Results also point to the need of identifying other possible risk factors for predicting CVD risk. Finally, initial body mass index is an important predictor of weight loss in this population group. Thus, indicating that this population is not only amenable to change, but that improvements in weight loss are feasible. This finding strengthens the relevance of prevention programs such as Beyond Sabor for Mexican populations at risk, in particular, food bank recipients.

Maternal gestational weight gain and offspring's risk of cardiovascular disease and mortality

Funding: This research was supported by Chest Heart and Stroke Scotland (R10/A128)