Accepting PhD Students

PhD projects

Evaluating the prevalence of primary aldosteronism in patients with stroke and/or atrial fibrillation Project description: Primary aldosteronism (PA) is the most common, and a potentially curable, cause of hypertension, estimated to affect 5-10% of all hypertensive patients. It leads to greater cardiovascular injury than hypertension alone. In particular, PA confers a 3 – 4 fold increase in the risk of stroke and atrial fibrillation compared to blood pressure-matched essential hypertensives. However, PA screening is not actively recommended in stroke/AF management guidelines. Given the potential health impact of diagnosing a potentially curable form of hypertension, and reducing the risk of stroke and AF, we seek to evaluate the prevalence of PA in patients presenting to Monash Health with either acute stroke or transient ischemic attack. This project has the potential to change management guidelines for hypertension in stroke patients and optimise the timely diagnosis of PA. Evaluating the cost-effectiveness of screening for PA in all vs subgroups of hypertensive patients Project description: Primary aldosteronism (PA) is the most common, and a potentially curable, cause of hypertension, estimated to affect 5-10% of all hypertensive patients. It leads to greater cardiovascular injury than hypertension alone. Studies have demonstrated the cost-effectiveness of screening patients with resistant hypertension for PA, but there are no economic modelling studies of screening newly diagnosed hypertensive patients. An early diagnosis is likely to be less complicated than in a patient with longstanding disease and offer greater benefit in reducing cardiovascular risk. However, without a formal cost analysis, hypertension screening guidelines will remain locked in the past to the detriment of our community. In this project, you will use the cost-utility analysis (CUA) approach to estimates the incremental costs and effectiveness of using ARR to screen for PA in primary care versus no screening. The within-trial analysis will be extrapolated using a Markov model, consisting of health outcomes following screening procedures versus no screening, to capture the long-term cost. The quality of life and direct medical costs will be collected from a current trial. The estimates of effect on long-run health outcomes, QOL and costs (such as cost savings of cardiovascular events averted) will be estimated from a comprehensive literature review. Sensitivity analysis will be performed to evaluate the cost-effectiveness of ARR screening in all vs subgroups of hypertensive patients. The outcomes will directly influence policy. Identification of novel transcriptomic markers of PA Project description: Whilst dichotomous thresholds are currently used to diagnose PA, emerging data supports the concept of a continuum of aldosterone excess. A longitudinal cohort study showed that higher aldosterone in the setting of a suppressed renin (392 of 850 normotensive patients) was significantly associated with the development of hypertension. A robust cellular marker of aldosterone excess that correlates strongly with clinical outcomes following MR antagonist treatment or adrenalectomy will complement the ARR and confirmatory tests in the diagnostic algorithm for PA. As peripheral blood monocytes highly express the MR, they represent an accessible MR-responsive tissue to study aldosterone-induced changes in gene transcription. A number of genes identified by previous students will be characterised in vitro using RT-PCR and cell culture to confirm a change in their expression in response to MR activation or antagonism. These may then be validated in larger patient cohorts as robust biomarkers of aldosterone excess and inappropriate MR activation. Establish a national PA registry to enable comprehensive data collection and multidisciplinary website Project description: Clinical registries play an important role in measuring healthcare delivery, supporting quality improvement and evaluating clinical outcomes, particularly in the long term. There are no PA registries in Australia. This is in contrast to other countries which lead the research in PA, including China (CONPASS PA Study Group – 3 publications in leading endocrine journals in 2018), Japan (JPAS – 6), Taiwan (TAIPAI - 8) and Germany (German Conn’s Registry – 10). Based on our existing REDCap database, we will develop a multicenter registry to systematically collect comorbidities, diagnostic parameters and long-term outcomes of patients with PA, both in and outside of clinical trials.


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