Periodic Reporting for period 5 - ENSAT-HT (Application of omics-based strategies for improved diagnosis and treatment of endocrine hypertension)
Reporting period: 2020-05-01 to 2021-12-31
Detection of secondary forms of hypertension is key to targeted management of the underlying disease and prevention of cardiovascular complications. Endocrine forms of high blood pressure (endocrine hypertension, EHT), such as primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) and Cushing’s syndrome (CS) represent the most frequent forms of secondary and curable hypertension and thus major targets for stratified approaches of hypertension (a tailored treatment based on the patient’s biological characteristics). However, diagnostic procedures for EHT are complex and require referral to specialised centres, which often delays the correct diagnosis. Consequently, appropriate treatment of the condition is either not initiated or delayed, with patients remaining exposed to increased risk of cardiovascular complications and a diminished quality of life.
The objective of ENSAT-HT project was to develop and evaluate an omics-based stratified health promotion program for patients with hypertension by identifying omics-based biomarkers allowing to diagnose endocrine forms of hypertension and to distinguish them from primary hypertension (PHT). Our final goal is to improve the identification of endocrine causes of hypertension for curative treatment and prevention of cardiovascular and metabolic complications as well as to stratify primary forms of hypertension for effective and cost efficient therapy.
In a first phase of our study, around 500 patients with endocrine and primary hypertension and 100 non-hypertensive controls have been included from already existing patient registries from specialist centres for adrenal disorder across Europe. The researchers then used cutting edge techniques to measure different omics features in blood and urine samples of these patients. ‘Omics’ is a term defining the collective characterisation and quantification of pools of biological molecules. We have then applied artificial intelligence approaches to implement a machine learning pipeline capable of identifying a signature that enables us to distinguish patients with endocrine hypertension and primary hypertension. A patent has been filed to protect those results.
In a second phase, a prospective study recruited more than 2000 patients with various types of hypertension in seven major expert European Hypertension centres, with the aim to use this data to refine the signature and to validate its diagnostic performances. As the identified signature from the retrospective study contains a high number of different molecules to be measured in the patients’ blood and 24h urine, this approach is also aimed to obtain a simpler set of biomarkers to allow the development of the multi-omics signature for a test easily usable in clinical setting.
An important issue for implementing a new test into clinical practice is of course its cost. Therefore, the ENSAT-HT project has also developed an economic model evaluating the costs of the omics tests for the diagnosis of endocrine hypertension compared to the current gold standard diagnostic procedure. A simple model was developed which considered the current costs of hospital-based workup for endocrine hypertension in each country as well as the risk of complications in undiagnosed patients.
In order to validate the approach of omics-based diagnosis of endocrine hypertension, we have designed a protocol for a randomised controlled clinical trial comparing the new omics-based procedure to standard of care. This trial will be the next step after the project for the further development of the identified omics signature to be translatable into a clinical setting.
Regarding the dissemination strategy, we communicated since 2019 on Twitter about the project by raising awareness about high blood pressure among the general public, but also retweeting the relevant posts from our pairs. Before the end of the project, it was essential for us to introduce our consortium through a series of threads and allow people to “meet” virtually the team members who took part in ENSAT-HT’s development. This last strategy leaves the door open for potential collaborations on the clinical setting of the identified omics signature.
This project will also have a strong impact on knowledge, by improving the understanding of the molecular and pathophysiological mechanisms involved in the most common forms of endocrine hypertension, allowing the redefinition of a novel, prognostically and therapeutically relevant disease taxonomy. In the future, patients' benefit will be derived from earlier, more precise and cost-efficient diagnosis, and from widespread availability of diagnostic tests outside from specialised referral centres, which has the potential to reduce health care disparity over the territory. Better informed medical decisions will improve therapeutic outcome thanks to better targeted therapies and earlier disease intervention, improving cure rate and quality of life while reducing comorbidities.
A decrease in health care costs is expected from the early detection and improved effective and cost efficient treatment of EHT at a subclinical stage and from prevention of cardiovascular and metabolic complications.