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A University of Otago – Ōtākou Whakaihu Waka researcher feels privileged knowing her work is treasured by the community she works with and in.

Dr Andree Pearson, of the Christchurch Heart Institute, Department of Medicine, Christchurch, is dedicated to improving heart health equity for Māori and Pacific peoples.

She has received more than $428,000 in the latest �Թ���վ Heart Foundation funding round for a Research Fellowship and two project grants. Her funding is part of the $1.5 million Otago researchers received from the Foundation this week for heart research and specialist training.

Dr Andree Pearson

“In the past two decades, the rates of heart disease in Aotearoa New Zealand have lowered across all ethnicities; however, rates of heart disease are declining less slowly in Māori and Pacific People indicating this inequity is, in fact, rising,” Dr Pearson says.

She is principal investigator for Hauora Manawa mō ngā Kaumātua me ngā Whānau (Kaumātua Manawa), a co-designed study based at several Christchurch marae which focusses on biomarkers of heart disease and echocardiography to directly assess heart health in older Māori.

The researchers have had an “overwhelmingly good reception” to not only undertaking a study specifically on Māori, but doing it in the community.

“Participants have enjoyed the relaxed nature as well as the feeling of being part of a greater good. I’d like to have an impact on Māori who have previously avoided going to hospital or the doctor and find by taking part in our study they realise our research is done by people who care about the people on the other side of medicines and treatments.

“We very much want to keep involved in the local Māori community with more research that serves them in the future,” she says.

Dr Pearson is also the Canterbury principal investigator for a unique collaboration between Otago’s Christchurch Heart Institute, researchers at the University of Auckland, and the Abdominal Aortic Aneurysm and Atrial Fibrillation Screening Project.

As part of this screening project, 900 Māori and Pasific participants are providing blood samples for measurement of specific cardiac biomarkers.

“Both of these projects will foster better understanding of cardiac biomarker concentrations and their relationships to heart disease in Māori and Pacific peoples.

“Cardiac biomarkers are central to diagnosing some cardiovascular conditions in routine clinical practice, however, diagnostic thresholds used in clinical practice have been derived in predominantly European and American cohorts.

“The distribution of biomarkers in Māori and Pacific peoples is largely unknown which can lead to significant underdiagnosis of heart failure for Pacific peoples, while it is unclear if the case is the same for Māori.”

Dr Pearson is “extremely grateful” to the Heart Foundation for supporting the projects.

“It is really great to use the funding in community projects that will benefit Māori, for whom heart disease is a big deal.”

Vice-Chancellor Grant Robertson congratulates Dr Pearson and all the Otago recipients on their funding success.

“It is fantastic to see such a great variety of research being funded, especially on such important mahi as heart health. I’m especially pleased to know the impact this work will have in reducing health inequities in our communities.”

The grants:

Research Fellowship

Dr Andree Pearson, Department of Pathology and Biomedical Science, Christchurch

Hauora manawa mō ngā kaumātua me ngā whānau | Heart health in older Māori and families

$300,392

There is urgency to address inequity in management of heart disease in New Zealand and to better understand any inter-ethnic biological differences that may contribute to disparities in health outcomes. This Fellowship will support her in developing her research career focusing on improving heart health equity for Māori and Pacific peoples reflected by a leadership role in two community-based projects. Dr Pearson is Principal Investigator for the Hauora Manawa mō ngā Kaumātua me ngā Whānau (Kaumātua Manawa), a study based at Christchurch marae aiming to assess and better understand the effect of age and ethnicity on heart structure and function in older Māori. This is a co-designed study focussing on biomarkers of heart disease and echocardiography to directly assess heart health in older Māori in the community. Study clinics are run at marae, generating a high level of engagement because time can be spent with individual participants in an environment in which they feel safe. Dr Pearson is also Canterbury PI for a unique collaboration between the Christchurch Heart Institute (CHI), researchers at the University of Auckland and the Abdominal Aortic Aneurysm (AAA) and Atrial Fibrillation (AF) Screening Project. As part of the AAA/AF Screening Project, 900 Māori and Pasific participants are giving informed consent to provide blood samples for measurement of specific cardiac biomarkers. Alongside the data obtained from the Kaumātua Manawa study, measurements from the AAA/AF study will foster better understanding of cardiac biomarker concentrations and their relationships to heart disease in Māori and Pacific peoples.

Senior Fellowship

Dr Nicola Scott, Department of Medicine, Christchurch

Heart Foundation Senior Fellowship

$288,306

The Heart Foundation Senior Fellowship will support Dr Nicola Scott in developing her research career centred around work with pre-clinical models of cardiovascular disease for discovery and validation of potential new therapies. Cardiovascular disease, a broad category of conditions including heart attack and heart failure, kills approximately one-third of New Zealanders. New treatments to improve outcomes for people living with heart disease are needed. Cyclic guanosine monophosphate (cGMP) is an important signaling molecule mediating the actions of the natriuretic peptides – heart hormones that can alleviate heart failure symptoms and improve outcomes. Levels of cGMP within cells are controlled by the balance between production and degradation/elimination. cGMP is broken down by an enzyme, phosphodiesterase-9 (PDE9), and/or eliminated by the action of a specific protein named multidrug resistance protein-4 (MRP4) that actively ‘transports’ cGMP out of the cell. Drugs that control or change the levels of cGMP within the cell have emerged as one of the most promising areas of cardiovascular drug discovery. Therefore, altering the activity of one or both of PDE9 or MRP4 offers therapeutic potential. In aim one: we will explore PDE9 inhibition as a novel treatment to prevent heart damage following a heart attack. We have previously shown that inhibiting PDE- 9 increases cGMP bioactivity with benefits in established heart failure. We now need to know whether adding PDE9 inhibitor to the most commonly prescribed heart failure medications, angiotensin converting enzyme (ACE) inhibitors, provides additive benefit (aim two). We will also explore inhibition of MRP4 to determine whether this can effectively treat heart failure (aim three). Findings from this research have the potential to be translated into new clinical treatment strategies for heart attack and heart failure.

Project Grants

Dr Simone Cree, Department of Medicine, Christchurch

Circulating cardiac troponin concentrations and associated genetic factors among Pacific and European community cohorts in Aotearoa

$200,000

�Թ���վ health data has shown that Pacific peoples have higher rates of hospitalisation from coronary heart disease than their non-Pacific counterparts. Although mortality from cardiovascular disease has been declining over the past few years, it has been declining more slowly in Pacific peoples, suggesting they have benefitted less from screening of cardiovascular biomarkers and management than other population groups. To address this disparity, Dr Cree and her team will assess whether blood tests used for the diagnosis of coronary heart disease are accurate for Pacific ethnic groups and investigate whether differences in the genetic code may explain why. Cardiac troponin concentrations are used as biomarkers to diagnose heart attacks, and higher concentrations of cardiac troponins have been reported in Māori/Pacific patients in New Zealand compared to New Zealand Europeans. They aim to determine community troponin concentrations among participants of the Pasifika Heart Study (n=200) and compare it to New Zealand European community cohort (n=2,500) to determine whether there are measurable differences in circulating troponins between New Zealanders of Pacific and European ancestry. They will also investigate the inherited genetic factors that influence troponin concentrations and cardiovascular disease risk in Pacific peoples and New Zealand Europeans using whole genome DNA sequencing. This study will evaluate the appropriateness of the current clinical interpretation of circulating troponin concentrations in Pacific peoples for the first time. By investigating the relationships between biomarker concentration and associated genetic risk factors, this project will identify opportunities to reduce health inequities for Pacific peoples and build evidence for improving coronary heart disease diagnosis and clinical outcomes for Pacific peoples in New Zealand. This work has the potential to lay the foundation for a national multi-centre study to evaluate current biomarker reference ranges for Pacific peoples.

Dr Lynley Lewis, Department of Medicine, Christchurch

Determinants of apparent plasma NT-proBNP concentrations in patients with heart failure

$198,187

Equitable health outcomes rely on clinical tests that work equally well for all New Zealanders. Diagnosis of heart failure (HF) and assessment of risk of deterioration or mortality often includes measurement of circulating concentrations of cardiac natriuretic peptides (NP), which increase with cardiac disease severity. Notably, NT-proBNP concentrations vary by ethnicity. They also decrease with obesity. We reported that Pacific peoples have lower plasma NT-proBNP concentrations than NZ Europeans. Separately the researchers reported that circulating precursor forms of B-type NPs differ between obese and non-obese patients with HF. These findings at least partly explain the lower concentrations of BNP and NT-proBNP observed with obesity, but not the lower levels observed in Pacific peoples. Intrinsically lower plasma NP concentrations may compromise diagnostic performance and risk stratification in patients with HF. Bioactive A-type and B-type NP concentrations increase in plasma when the heart is stressed. In addition to multiple clinical and demographic factors, NP concentrations are influenced by altered secretion and cleavage of precursor forms, and altered clearance of active forms. Associations between A- and B-type forms are not well defined. The research team has previously measured multiple B-type NP forms (proBNP, BNP and NT-proBNP – with or without glycosylation) in plasma obtained from patients with HF, and propose to complement this by measuring multiple A-type NP forms, cleavage enzyme concentrations and second messenger (cGMP) concentrations in the same plasma samples. Results will enable the researchers to determine where in the NP pathways the reduction is occurring and how NPs and cGMP concentrations are affected by these changes. Increased understanding of pathways involved in determining circulating levels of NPs will provide clear rationale for later larger scale comparisons of diagnostic and prognostic performance within subgroups of patients and will provide an avenue to investigate the NP biochemistry behind newly developed HF treatments that target the NP pathway.

Dr Andree Pearson, Department of Pathology and Biomedical Science, Christchurch

Assessing proBNP in Māori and Pacific Peoples

$107,616

Cardiac biomarkers are central to diagnosing some cardiovascular conditions in routine clinical practice. Yet diagnostic thresholds have been derived in predominantly European and American cohorts and the distribution of biomarkers in Māori and Pacific peoples is largely unknown. The evidence available to date suggests the diagnostic thresholds used in clinical practice will lead to significant underdiagnosis of heart failure for Pacific peoples, and it is unclear whether this is the case for Māori. This project will characterise the variation in biomarkers, particularly NT-proBNP, for Māori and Pacific peoples in New Zealand, which is crucial to ensure they are used equitably in clinical practice.

Research Associate Professor Anna Pilbrow, Department of Medicine, Christchurch

Discovering copy-number variants that influence risk of disease and poor outcomes in acute coronary syndromes

$197,514

Coronary artery disease can lead to a heart attack due to an abrupt loss of blood supply to part of the heart muscle, and may be followed by any of number of complications that together comprise coronary heart disease. In Aotearoa New Zealand, one in 20 adults live with coronary heart disease, and this leading cause of mortality and morbidity accounts for ~5,000 deaths each year. It is estimated that up to 50 per cent of susceptibility to coronary heart disease is inherited. Over the last 15 years, rapid advances in technology have facilitated the discovery of more than 150 regions of our DNA as risk factors for coronary heart disease. However, even when combined, currently known DNA variations account for a relatively small proportion of inherited susceptibility to coronary heart disease. A source of the ‘missing heritability’ may be DNA copy-number variation, an important type of DNA variation that has, up until recently, been difficult to explore due to methodological limitations. In this project, the researchers aim to understand how DNA copy-number variants (large deletions or duplications of DNA) influence susceptibility to coronary heart disease in New Zealand. First, we will determine whether selected copy-number variants occur more frequently in New Zealanders with acute coronary syndromes than heart-healthy controls. Second, we will test if copy-number variants occur more frequently in coronary patients who have recurrent events or die after being discharged from hospital. Finally, they will undertake detailed genetic analyses in a small number of patients who have copy-number variants to help us locate precisely how the DNA sequence is altered and how it may influence disease risk. Findings from this project have the potential to advance personalised management and treatment strategies for heart patients and provide new knowledge on the mechanisms underlying inherited susceptibility to coronary heart disease.

Dr Nicola Scott, Department of Medicine, Christchurch

Combined inhibition of Phosphodiesterase 9 and Angiotensin Converting Enzyme in experimental heart failure

$118,396

Heart failure (HF) remains a leading cause of death and disability in New Zealand, and new treatments are needed. Taking medication that blocks the action of the hormone system known as renin-angiotensin-aldosterone system (RAAS) is currently the cornerstone of HF treatment and the most commonly prescribed pills are Angiotensin-converting-enzyme inhibitors (ACE-I). The heart hormones, natriuretic peptides (NPs) play a fundamental role in regulating blood pressure and fluid volumes in the circulation with their actions constituting a beneficial compensatory mechanism in HF. Dual medications that combine RAAS-blockade with actions to enhance NP action through blocking the enzyme neprilysin – has emerged as a better approach. However, neprilysin inhibition has additional actions that may be undesirable. An alternative method of enhancing the beneficial actions of the NPs is to inhibit another enzyme known as phosphodiesterase-9 (PDE9). This is a more specific way of enhancing NP actions and is under trial as a viable treatment for patients with HF when combined with RAAS blockade. Dr Scott and her team aim to assess the efficacy of inhibition of PDE9 versus ACE-I as HF therapies using a sheep model – comparing their separate and combined effects to test whether combined treatment offers greater benefit than either treatment alone. This study will provide new knowledge, helping define the therapeutic potential of PDE9 inhibition in HF as an additive therapy to ACE-I. This may lead to an improved treatment for HF using combination therapy with these two agents.

Postgraduate Scholarship

Mr Jekhan Saravanan, Department of Physiology

$76,482

Billions of heart cells die following a heart attack, a major reason why heart disease has a high global mortality rate. The heart struggles to repair itself because it can’t regenerate these cells effectively. Current available treatments do not work well in restoring these damaged cells. As the disease advances, the dead cells are replaced with scar tissue. This scar tissue lacks mechanical strength and cannot transmit electrical pulses, ultimately impacting the ability of the heart to contract. The recent discovery of the crucial role of small gene regulatory molecules called microRNAs (miRNAs) in controlling myocardial repair post-ischemia has opened a new area of regenerative therapy. However, getting these miRNAs into the heart cells is challenging.

Mr Saravanan’s study focuses on developing a new solution to overcome this barrier. He will encapsulate the miRNAs into lipid nanoparticles, which have been effectively used as a drug delivery carrier; the nanoparticles will then be incorporated into biodegradable scaffolds. The scaffolds are the structures that can support new cell growth, made from materials that can conduct electricity and respond to mechanical stress. These scaffolds are designed to mimic natural heart tissue and help attach, grow, and mature new cells. Incorporation of miRNA-encapsulated nanoparticles into the biodegradable conductive scaffold will help restore the heart’s ability to contract in a coordinated way by improving how the heart cells communicate with each other. This study will provide foundational evidence for developing a new therapy for patients with heart failure, setting the stage for future pre-clinical studies to evaluate its efficacy and safety before clinical application. If successful, this therapy could enable individuals with heart failure to live fuller lives by alleviating disabling symptoms such as exercise intolerance, fatigue, and shortness of breath.

Small Project Grant

Dr Sarah Appleby, Department of Medicine, Christchurch

CNDP2: a potential new marker for poor outcomes in heart failure

$19,926

During heart failure, an injured or overloaded heart struggles to pump sufficient blood around the body to maintain the normal function of organs and tissues. It affects approximately 121,000 New Zealanders, is the single most frequent reason people aged over 60 years are admitted to hospital and is a leading cause of death. When the heart is under this increased stress, the oxygen supply for energy usage can be low, causing the heart to switch to a different energy source to continue functioning. This results in lactate as the primary by-product. While lactate is a crucial energy source for the stressed heart, excess lactate in the blood has been linked to increased mortality and poor cardiovascular outcomes, and rapid lactate clearance is associated with increased survival, although the mechanisms behind this are unclear. Thus, this project will investigate a novel mechanism of lactate clearance mediated by the enzyme carnosine dipeptidase II (CNDP2) in both healthy individuals and those with heart failure. Dr Appleby and her team will determine if CNDP2 protein is present in human heart tissue and whether circulating CNDP2 is coming from the heart. They will investigate if circulating levels of CNDP2 are altered in heart failure and associated with adverse outcomes. Therefore, this study will produce new knowledge on how lactate is cleared in heart failure and may lead to novel strategies for the management and treatment of patients with heart failure.

Dr Laura Joyce, Department of Surgery and Critical Care, Christchurch

Remote follow-up for Atrial Fibrillation patients post Emergency Department attendance

$16,400

This project aims to provide equitable access to high quality emergency and specialist care for patients with atrial fibrillation (Te Pae Tata). It utilises remote follow-up via a smartphone application measuring heart rhythm, assisted by a nurse-led telephone call, and could negate the need for unnecessary procedures or hospital admission for this patient group. Atrial fibrillation (AF) is the most common abnormal heart rhythm in adults, with the majority of patients who present to the emergency department with AF across Australasia having a procedure to return their heart to a normal rhythm (cardioversion), and/or being admitted to hospital. Christchurch Emergency Department uses a clinical AF pathway shown to safely reduce unnecessary cardioversions/hospitalisations. Currently this patient group is followed up in an off-site clinic the next day, and either return to hospital for delayed cardioversion, or have expedited ongoing community management. Patients managed via this pathway report positively on the experience. This feasibility pilot aims to assess whether remote follow-up could be used to screen patients next-day in their own home, negating the need to attend clinic in-person. This would occur in parallel to standard care. Patients would be loaned a smartphone and would receive a phone call the next morning asking them to report their symptoms and use a smartphone application which detects AF by simply lying down with the phone on their chest for one minute. Feedback on the usability and acceptability of the process will be sought to gain an in-depth understanding of the patient experience of the remote follow-up process. If this pilot proves successful then a future NZ-wide trial is planned to implement this clinical AF pathway in multiple centres, with the option of remote follow-up provided centrally, of particular benefit to rural communities/sites without cardiology specialists.

Professor Rachael McLean, Department of Preventive & Social Medicine

Development of a potassium enriched reduced sodium bread: a population approach for reducing blood pressure and improving heart health

$7,366

Heart disease is a leading cause of death and disability in Aotearoa New Zealand. High blood pressure substantially increases the risk of heart disease and stroke. Although many people can take medication to control high blood pressure, lowering everybody’s blood pressure will reduce heart disease across the population. A diet that contains too much sodium (salt) or too little potassium (primarily from fruit and vegetables) can increase blood pressure. Replacing ordinary table salt with a salt substitute that has reduced sodium and added potassium can help reduce blood pressure and heart disease. This research explores whether this salt substitute can be used in bread without changing texture or taste, and whether people are happy to use this bread in their everyday lives. Professor McLean and her team will use the food science laboratory at the University of Otago to test several concentrations of salt substitute in bread, and formally assess the physical qualities of the bread as well as its taste. They have arranged to work with food provision staff at Puketeraki Marae to see if kaumātua and whānau are happy to include this healthier bread in their homes over a two-week period. This research will inform public health measures to improve blood pressure and heart health. It aligns with existing work undertaken by the Heart Foundation to reformulate foods so that there is less salt and sugar in the New Zealand food supply.

Dr Andree Pearson, Department of Pathology and Biomedical Science, Christchurch

Hauora Manawa mō ngā Kaumātua me ngā Whānau | Heart Health in older Māori and Families

$20,000

In the past two decades, the rates of heart disease in Aotearoa New Zealand have lowered across all ethnicities; however, rates of heart disease are declining less slowly in Māori and Pacific People indicating this inequity is, in fact, rising. To address inequity, the Christchurch Heart Institute has initiated engagement with local Māori communities with the aim of improving relationships and co-designing research around heart disease. Dr Andree Pearson is working with the Māori Governance Rōpū of a study entitled Hauora Manawa mō ngā Kaumātua me ngā Whānau (Kaumātua Manawa), a codesigned marae-based community project, to assess and better understand heart health of kaumātua (older Māori) in the local Māori community. This project has a focus on biomarkers used to diagnose and stratify heart failure and heart attacks as well as echocardiography measurements. Dr Pearson and her team are particularly interested in whether ethnicity contributes to differences in levels given reference ranges for biomarker and echocardiography indices are based on a predominantly European population and it is not known how well they work for Māori. This study also will help demystify heart disease research in a marae-based setting and aims to provide a better understanding of cardiovascular disease risk in older Māori in the community.

Kaumātua Manawa is already underway, utilising funding from the New Zealand Heart Foundation, Pūtahi Manawa (A Centre of Research Excellence) and Lottery Health Research. The researchers have run six clinics to date at two marae in Christchurch, with 27 participants, and are currently engaging with kaumātua groups at other marae to widen the reach of the study. This small project grant application is for transport of staff and equipment to marae, and costs relating to visits to kaumātua.

Grant-in-Aid

Dr Rory Miller, Department of General Practice and Rural Health

Improving Care in Rural and Urgent Care centres for patients with possible Acute coronary syndrome using the Latest point-of-care troponin (I-Care RURAL POC)

$14,927

Currently patients that present to most rural and other community-based health facilities do not have access to the same highly precise and sensitive blood tests used to investigate chest pain suspected to be from a cardiac cause. Although current technology is safe for patients who have chest pain and are at low risk of having a myocardial infarction, a clinical assessment pathway using a novel high-sensitivity point-of-care troponin test will speed this assessment process and allow rapid identification of low-risk patients allowing investigations to safely occur in the patient’s community in rural general practice, urgent care and rural hospital settings. Dr Miller and his team anticipate this will safely reduce the number of patients that will require (often lengthy) transfer to hospital allowing people to remain in their communities. This project will evaluate the new pathway and compare it to current practice. It will measure the length of stay at health facilities, safety, reduction in transfers and new heart attacks diagnosed that were previously missed. There will also be a qualitative assessment of the implementation process, an economic evaluation, and an examination of the risk factors for heart attacks in the study population with chest pain using data obtained throughout this study. Successful completion of this project will result in the pathway using point-of-care testing to be implemented in many different settings, including in rural and community contexts throughout Aotearoa New Zealand, which will enable residents that do not live close to urban hospitals to get access to gold standard investigations. This is likely to meaningfully reduce the number of patients that require referral and transfer to urban hospital emergency departments, reducing overcrowding and the burden of care for these facilities.