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Transcript
Hormones hold hope in heart disease Hormones released into the body as the result of heart disease may offer clinicians a powerful tool in the diagnosis and treatment of cardiac conditions. The Christchurch School of Medicine’s Cardioendocrine Research Group, led by Professor Mark Richards, has established an international reputation for work on the relationship between hormones and cardiac stress and injury such as heart attack. Their biggest project is a clinical study involving 2000 patients, with coronary problems ranging from unstable angina to a full-blown heart attack, in which they have been measuring various hormones generated by the heart and other vascular tissue, as well as the kidneys, adrenal glands and brain. “We know from existing experience that in certain subgroups of heart disease these hormones are powerful indicators of the severity of heart disease and the patient’s risk of deterioration. What we don’t know is how well we can apply those measurements across a very broad group. By coupling hormone measurements with measurements of the heart by echocardiography, the team are developing a set of markers for assessing whether people are at low, medium or high risk of further problems. Another of the group’s projects is looking at subtle variations in genes, which may alter people’s susceptibility to heart problems and their ability to compensate for heart injury. While some people seem good at compensating for quite large injuries others seem to deteriorate rapidly. The research team has recently discovered a common variant form of the angiotensin converting enzyme (ACE) gene, which is associated with an eight-fold increase in mortality over five years following a heat attack. In future, knowing the form of the ACE gene may lead to early intervention and improved survival. Professor Richards and his team are also developing ways of measuring newly discovered hormones so they can look at their levels in different patient groups. Hormones from the urocortin family are of particular interest because they are already known to give considerable benefit to damaged hearts in sheep, and the team is keen to see what they do in patients with cardiac failure. The therapeutic potential of hormones such as urocortin are also being investigated to see how they influence nervous traffic to the heart. The team is examining the interaction of the sympathetic nervous system with the heart, kidneys and hormones. It has a lot to do with how fast the heart beats, as well as blood vessel tone and blood pressure. Over the past two years the group has lodged three patent applications with the NZ Patent Office. The group is currently collaborating with pharmaceutical companies in six ongoing studies, including phase I, phase II and phase III trials. This research is funded by the Health Research Council of New Zealand, the University of Otago, the National Heart Foundation, the Canterbury Medical Research Foundation and the Lottery Grants Board, and with support from the pharmaceutical industry. HRC19 2004 Level 3, 110 Stanley Street, Auckland PO Box 5541, Wellesley Street, Auckland, NZ Telephone 64 9 303 5200 Facsimile 64 9 377 9988 Website www.hrc.govt.nz Health Research Council of New Zealand Te Kaunihera Rangahau Hauora o Aotearoa Dr Tim Yandle, Professor Gary Nicholls, and Professor Mark Richards Key words: – cardiovascular disease, hormones, ACE gene variants. Key facts about cardiovascular disease in New Zealand: – leading cause of death (40%), estimated to cost $306m- $467m in early 1990s. Two to three times higher death rate for Maori. Aims of our research are to: – better establish predictors of the risk of onset of heart failure – trial early interventions in the groups discovered to be at risk. What this research has shown: – identified two cardiac natriuretic peptide hormones as the strongest prognostic markers of new cardiac events in patients who have already incurred heart attack or heart failure – patients with heart failure most likely to respond to beta blockade are those who have high pretreatment hormone level – results of a piloted heart failure treatment guided by blood hormone levels demonstrated that this strategy may substantially reduce mortality and hospital readmission rates.