MECHANISMS OF CEREBROVASCULAR REGULATION IN HEALTH AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$216,430.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the degree of opening of the cerebral arteries. This mechanism involves activation of an enzyme, Rho-kinase, which is present in the wall of blood vessels. The applicants believe that this process plays an important role in the normal, healthy regulation of blood supply to the brain. Moreover, there are strong reasons for us to speculate that the function of this enzyme is abnormally high in two disease states that are associated with an increased risk of stroke - high blood pressure and subarachnoid haemorrhage. We will employ a variety of techniques to assess the importance of Rho-kinase in cerebral artery function in the living body, and also in isolated segments of artery. The results are expected to provide major new insight into mechanisms that regulate brain blood flow, and the knowledge gained here may lead to better therapies to prevent or treat stroke.Read moreRead less
An Implementation Trial Of A Telephone-based Care Management Program For Patients Following Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$641,656.00
Summary
We are trialling the implementation of an innovative telephone-delivered program for managing people who have had a heart attack. Cardiac rehabilitation programs are generally based in hospitals in Australia and people have to be able to attend the programs when they are offered. Even though such programs have been shown to be very effective in improving outcomes after a heart attack, at least 85% of Australians after a heart attack are either unable to access and-or unable to attend such progra ....We are trialling the implementation of an innovative telephone-delivered program for managing people who have had a heart attack. Cardiac rehabilitation programs are generally based in hospitals in Australia and people have to be able to attend the programs when they are offered. Even though such programs have been shown to be very effective in improving outcomes after a heart attack, at least 85% of Australians after a heart attack are either unable to access and-or unable to attend such programs due to transport and many other barriers. So, there is an urgent need to identify new, effective, and affordable ways of delivering cardiac rehabilitation programs to people after a heart attack. The proposed telephone-delivered program will be particularly appropriate for disadvantaged people, such as those living in rural and remote areas as well as Indigenous Australians, who do not currently have access to hospital-based cardiac rehabilitation programs. People who have had a heart attack will be recruited from three of Brisbane's largest public teaching hospitals, and will then be randomly assigned to the telephone-delivered cardiac rehabilitation program (Care Management Intervention group) or to a control or Usual Care group. The Care Management Intervention group will receive regular telephone calls from a highly qualified 'Care Manager' based at the renowned National Heart Foundation of Australia telephone support service, 'Heartline'. The Care Manager will help people to manage their heart condition and prevent the reoccurrence of further heart problems. People will also be encouraged to make necessary lifestyle and behavioural changes with the assistance of the Care Manager and some Heart Foundation educational and interactive resources to record their progress. We expect that the program or Care Management Intervention group will have better health outcomes than the control or Usual Care group at 6 and 12 months follow up.Read moreRead less
The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for matching energy supply to energy demand by the many different cells in our bodies. AMPK is active in the heart, where it may control cardiac function and the response of the heart to disease. It has been difficult to study AMPK in the heart because we lack drugs that block the actions of AMPK. This study will investigate the role of AMPK in the heart using a genetic approach whereby the AMPK enzyme is re ....The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for matching energy supply to energy demand by the many different cells in our bodies. AMPK is active in the heart, where it may control cardiac function and the response of the heart to disease. It has been difficult to study AMPK in the heart because we lack drugs that block the actions of AMPK. This study will investigate the role of AMPK in the heart using a genetic approach whereby the AMPK enzyme is rendered inactive (a gene knockout approach). By this approach we will learn how AMPK controls heart function and how drugs that affect AMPK may impact on the heart.Read moreRead less
Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a subst ....Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a substantial group of patients are therefore at risk of an adverse outcome following surgery. Despite the magnitude of this problem, however, few studies have established treatments to decrease the risk of complications and death following surgery. Beta-blockers are a group of drugs which have been used for decades in the treatment of heart disease and high blood pressure. Beta-blockers are known to improve the way the heart copes with the stress of surgery. They decrease the heart rate, make the heart more efficient at using energy and reduce the likelihood of imbalance between oxygen supply and demand. Some previous studies showed that beta-blockers may reduce the risk of heart attack and death for up to 2 years after surgery. However, other studies have shown no effect of beta-blockers on outcome. These previous studies have involved small numbers of patients who may not represent the broader population having surgery. We therefore are undertaking a large trial to definitively answer the question about whether beta-blockers improve the outcome after non-cardiac surgery in patients with, or at risk of, heart disease. Even if the effect of beta-blockers is relatively modest, because such large numbers of patients with heart disease have surgery, the overall effect on the rate of complications and death in the population could be very significant. The results of this study could have major implications for the success of, and cost of, surgery worldwide.Read moreRead less
Novel Approaches To Risk Stratification In Patients With Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$508,838.00
Summary
75% of the mortality in adults with Type 2 diabetes is due to a cardiac event. Early detection and treatment of cardiac disease is paramount in improving health outcomes. An echocardiogram is an accurate and non-invasive identification of cardiac dysfunction. We will assess the prognostic value of echocardiography and novel plasma markers in patients with diabetes. Our results may lead to new management and screening guidelines for heart disease in diabetes.
Nox4-containing NADPH-oxidase As A Protective Enzyme In The Cerebral Circulation
Funder
National Health and Medical Research Council
Funding Amount
$515,812.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activa ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activation of an enzyme, Nox4-containing NADPH-oxidase, to generate oxygen radicals which then relax the wall of blood vessels causing the arteries to let more blood through. We believe that this process plays an important role in the normal, healthy maintenance of blood supply to the brain. Furthermore, we propose that the activity of this enzyme is elevated and therefore protective in brain arteries during high blood presure - which is the major risk factor for stroke. We will specifically test whether the activity of this enzyme actually helps to limit the amount of brain death following stroke. We will use a variety of techniques to assess the importance of this enzyme in brain arteries in the living body, and also in isolated segments of brain artery from animals that are either healthy or have diseased brain arteries. The results are expected to provide major new insight into processes that help maintain brain blood flow under normal conditions and after a stroke, and the knowledge gained here should lead to safer therapies to prevent or treat stroke.Read moreRead less
Genetic Markers For Retinal Arteriolar Narrowing And Risk Of Hypertension And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$438,991.00
Summary
This submission proposes a study to identify the genes that determine retinal arteriolar narrowing - a marker of hypertension, and to examine how these genes interact with environmental factors, and to investigate if these genes do indeed predict persons at risk of heart disease.
Ankle Brachial Index Determination By Oscillometric Method IN General Practice (ABIDING)
Funder
National Health and Medical Research Council
Funding Amount
$128,935.00
Summary
People who have peripheral arterial disease (PAD) have blockages of the circulation to their legs. If you have PAD you have blood vessel disease throughout the body and are very likely to have a heart attack or experience a stroke. PAD can be diagnosed simply by comparing the blood pressure in the arms and legs. Until now this needed a special costly instrument. New blood pressure machines can do this without this instrument. We want to know how reliably this can be done by practice nurses.
The proportion of the population over 65 years of age is increasing, and cardiovascular disease (CVD) is a leading cause of disability and death in this group of people. Angina, heart failure and stroke in elderly people often result in considerable disability and in many instances in a need for changed living circumstances such as admission to nursing homes. Consequently there is an important need to understand how to prevent and manage cardiovascular diseases in elderly people. Although CVD oc ....The proportion of the population over 65 years of age is increasing, and cardiovascular disease (CVD) is a leading cause of disability and death in this group of people. Angina, heart failure and stroke in elderly people often result in considerable disability and in many instances in a need for changed living circumstances such as admission to nursing homes. Consequently there is an important need to understand how to prevent and manage cardiovascular diseases in elderly people. Although CVD occurs much more frequently in older persons, much of the epidemiological information on CVD risk factors and risk estimation comes from studies of middle-aged populations. Recently there has been an increased focus on whether the established relationships hold or differ in the elderly. This has generated debate about the relative value and effectiveness of treating risk factors in elderly people. This study, which is based on comprehensive and long-term risk factor, mortality and morbidity data from the Busselton Health Study and Health in Men Study, will lead to a better understanding of classic and new CVD risk factors in older persons and will contribute positively to the debate about the relative value and effectiveness of attempting to modify risk factors in the elderly. Further, it will facilitate improved methods for CVD risk assessment in older people and hence assist in determining whether which preventive actions to implement in the elderly.Read moreRead less
Assessing Cardiovascular Disease (CVD) Risk In Aboriginal People
Funder
National Health and Medical Research Council
Funding Amount
$73,550.00
Summary
Aboriginal Australians have higher death rates from cardiovascular disease (CVD) than other Australians, with rates in young and middle aged people increased 15-fold or more. A multi-factor approach, which considers all the risk factors, is the best strategy to identify and reduce CVD risk. The first step for selection of risk-reduction therapy in an individual is to assess his-her risk status and the benefit of intervention. Several risk assessment tools, incorporating traditional risk factors, ....Aboriginal Australians have higher death rates from cardiovascular disease (CVD) than other Australians, with rates in young and middle aged people increased 15-fold or more. A multi-factor approach, which considers all the risk factors, is the best strategy to identify and reduce CVD risk. The first step for selection of risk-reduction therapy in an individual is to assess his-her risk status and the benefit of intervention. Several risk assessment tools, incorporating traditional risk factors, have been developed from Western populations. They would be most appropriately applied to individuals who resemble the study sample; their validity in Aboriginal Australians has not been evaluated and no risk prediction formulae have been developed specifically for Aboriginal people. Recent reports suggest that a variety of other non-traditional risk factors also influence CVD risk, including markers of central fat deposition, inflammation, nutrition, alcohol use and early growth. Given the disadvantaged circumstances of many Aboriginal people, it is likely that some of the factors are influencing their CVD risk. The applicants have collected baseline risk factor data on volunteers in one Aboriginal community and followed their course, including CVD deaths and CVD hospitalisations, for more than a decade. From this baseline information, which goes beyond traditional risk markers, and from additional measures like birthweight, and markers of inflammation and nutrition assayed in retrieved serum, we will develop a variety of models for predicting a CVD risk in this group. We will also lay plans to evaluate these tools in other Aboriginal groups. A better understanding of the causes of CVD in this population is important to influence public health policy for CVD prevention. The models will be helpful health education tools at the community level and will allow therapeutic or lifestyle intervention in individuals to be targeted at their individual risk profile.Read moreRead less