Primary Aldosteronism Centre of Excellence (PACE)
Optimising the diagnosis and management of a potentially curable form of hypertension
Primary aldosteronism is a major public health issue
Hypertension is a leading risk factor for death and disability globally with the condition causing an estimated 10.3 million deaths and 208 million disability-adjusted life years in 2013 (1). In 2014-2015, close to 6 million adults (34%) in Australia were affected; 4.1 million of these (68%) had uncontrolled or untreated hypertension. The National Heart Foundation (2016) states that “despite strong evidence for the benefits of treating hypertension, controlling raised blood pressure at a population level remains a large national challenge”.
A substantial impact on this challenge can be made by addressing the under-diagnosis of an eminently treatable and potentially curable cause of hypertension – primary aldosteronism (PA), a condition of excessive aldosterone production from the adrenal gland. PA confers much greater cardiovascular risk than blood pressure-matched essential hypertension (2), but has targeted treatments: it is either curable with minimally invasive surgery in the case of a unilateral aldosterone-producing adrenal adenoma (APA), or can be effectively treated with mineralocorticoid receptor (MR) antagonists (MRA) such as spironolactone in the case of bilateral adrenal disease (3). An early diagnosis is associated with a greater likelihood of clinical cure and reduced end-organ damage (4).
The problems facing patients who are affected by PA and the community overall
- PA is substantially under-diagnosed due to the lack of screening guidelines for hypertensive patients either in primary care or in high risk groups, such as those with atrial fibrillation, stroke or obstructive sleep apnoea. Based on international data, PA may affect 10 – 20% of the hypertensive population; yet local Australian data suggests that less than 0.1% of hypertensive patients in primary care have received this diagnosis (5). It is estimated that as many as half a million Australians with hypertension go undiagnosed and therefore miss out on potential curative treatment. This must contribute to the growing burden of uncontrolled hypertension and consequent cardiovascular disease (CVD).
- The diagnosis of aldosterone excess as a cause of hypertension is challenging in complex clinical situations (6, 7), with a need for improved or alternative diagnostic tests.
- The recent explosion in knowledge about the genetic basis of PA (8-11) remains to be translated into clinically useful tests or personalized therapeutics.
- There is limited clinical trial capacity for novel MRA in development, despite the potential benefits of a more potent, specific and targeted treatment for a significant portion of hypertensive patients.
The problems are starting to receive international recognition; Australia can lead the way
The latest randomised controlled trial of treatment-resistant hypertension, PATHWAY-2, singled out spironolactone as the most effective add-on therapy and identified up to 38% of its trial participants as having previously undiagnosed PA (12). This finding supports the statement that PA is a “major public health issue” in the 2016 Endocrine Society Guidelines (13). Increasing research effort has been spent on PA in America, Germany, Italy, France, China, Taiwan and Japan where large PA research consortiums exist and contribute substantially to the current research output, although none have adequately addressed the four issues above. Furthermore, their results are not directly comparable to Australia due to our unique multicultural and indigenous populations. High-quality innovative PA research is conducted in several Australian centres and we can lead the world in this area if we had a network that can facilitate timely translation, enhance research workforce capacity, maximize consumer input or coordinate large scale clinical trials.
- Optimise the timely and accurate diagnosis of PA through high quality, collaborative research and transformation of clinical practice guidelines and diagnostic methods;
- Identify novel genetic factors that will translate into personalized diagnostic tests and therapeutics in the prevention and management of PA; and
- Create translational research environments and develop clinical trial platforms to build the capacity for world-leading PA research by Australian clinicians and scientists.