Thanks to the Short Term Scientific Mission (STSM) of the VascAgeNet COST Action I had the opportunity to participate in the activities of the vascular lab at INSERM and to acquire knowledge about new techniques for the assessment of vascular ageing on small- and medium-sized arteries, and in particular Ultra-High Frequency Ultrasound (UHF-US), an advanced technique that make it possible for the first time to non-invasively and accurately assess hand vasculature thanks to frequencies up to 70 MHz, and 3-D ultrasound (tUS).

The application of these techniques is valuable for the evaluation of hand vascular involvement in Systemic Sclerosis (SSc), a disorder characterized by alterations of the microvasculature, including digital ulcers and Raynaud’s phenomenon, in a protocol currently ongoing at INSERM.

During this STSM, images of the digital arteries of 15 SSc patients were processed thanks to a validated high-precision contour tracking algorithm for the estimation of structural and elasticity parameters of digital arteries (diameter, distension and border thickness) by ultrasound image processing.

The study and monitoring of structural parameters of the digital arteries could be relevant in the exploration of reliable imaging biomarkers for the diagnosis and pathogenesis of SSc as well as for the control of the therapies administered to patients and the related effects on the progression of the disease.

Furthermore, the results achieved thanks to this STSM will allow to evaluate the possible connection between peripheral and systemic vascular diseases.

Further information is available at the website https://vascagenet.eu/short-term-scientific-missions

Alicia Del Saz Lara performed a three-months STSM at the National Institute of Health and Medical Research (INSERM), Paris, under the supervision of Dr. Rosa Maria Bruno. The main object of the STSM was to perform a systematic review and meta-analysis aimed to analyze the association between pulse wave velocity and incident hypertension. Additionally, she participated in activities that took place at INSERM during her stay in Paris.

The work was developed as a result of the combination of the expertise of both groups, on the one hand the clinical knowledge of arterial stiffness and hypertension by the INSERM group of Paris, France, and on the other hand the expertise in performing of systematic reviews and meta-analysis of the CESS group of Cuenca, Spain.

After a careful electronic search carried out in the principal electronic databases, two independent reviewers examined inclusion and exclusion criteria of each selected longitudinal study. The main information of included studies were extracted, and the meta-analysis was performed according to advanced and up-to-date statistical technologies.

Results demonstrated that increased pulse wave velocity, systolic blood pressure and diastolic blood pressure are all predictors of incident hypertension in normotensive adult subjects, with similar independent predictive value. This analysis is projected to be the first systematic review and meta-analysis of arterial stiffness and baseline blood pressure in the normotensive range as predictors of incident hypertension. A paper is currently under writing.

“Thanks to Dr. Cavero-Redondo I started researching in the field of vascular health. The VascAgeNet STSM offered me the opportunity to acquire new knowledge on this topic, as well as to meet researchers such as Rosa Maria Bruno, who has been the link for future collaborations of both research groups. I am very excited and eager to continue working in this world of vascular health”, said Alicia.

Her stay in Paris generated future collaborations to establish Early Vascular Ageing (EVA) as a construct measurable by clinicians. A series of meetings are pending between the INSERM and CESS groups to establish further research projects.

Dr Peter Charlton spent 5 days at Kaunas University of Technology (KTU), hosted by Prof Vaidotas Marozas, Director of the Institute of Biomedical Engineering. Vaidotas and Peter are members of VascAgeNet’s Working Group 3. They’ve previously collaborated on several projects including a VascAgeNet review of techniques to assess vascular age from the photoplethysmogram (the PPG – the pulse wave signal measured by smartwatches and activity trackers). During this STSM, Vaidotas and Peter worked with colleagues at KTU towards harmonising photoplethysmography-based techniques for the assessment of vascular ageing.

First, Peter and colleagues worked on developing PPG signal processing techniques for the assessment of vascular ageing. Specific tasks included: designing approaches to estimate blood pressure from the PPG pulse wave signal; developing PPG signal quality assessment tools which could help ensure that vascular ageing assessments performed in daily life are reliable; and investigating how well PPG signal processing algorithms perform with different types of sensors. This involved sharing knowledge, data, and signal processing algorithms.

Second, Peter and colleagues discussed the designs of two ongoing clinical studies at KTU and at the University of Cambridge. They identified ways to harmonise the methods used in the two studies so that they provide similar datasets. It is hoped that this will enable the two groups to test the generalisability of findings across the two datasets.

Third, Peter and colleagues established a pipeline for simulating PPG signals containing artifact and arrhythmias. This involved using KTU’s tools for simulating PPG signals alongside data collected at the University of Cambridge. It is hoped that this will lead to the creation of a dataset of simulated PPG signals representative of those that would be measured from older adults in the community.

Peter received very warm hospitality from Vaidotas and his colleagues at KTU, sharing meals and sightseeing together. This helped Peter get to know his new colleagues well during a short space of time, establishing relationships which will enable them to continue to work together remotely.

My name is Ana Belen Amado Rey and I am doing my Postdoc at the technical university of Freiburg, in Germany. My research focuses on the development of new ultrasound technologies and techniques to derive blood pressure and the arterial stiffness at various arterial sites (carotid, brachial, radial). By using high accurate diagnose devices the risks that may lead to cardiovascular diseases can be better diagnosed and prevented in time.

Last year I could validate the accuracy of various stiffness and blood pressure models for ultrasound by using in vitro and ex vivo cardiovascular setups in our laboratory. However, I do not have access to real data to validate those models in vivo. Thanks to the Short-Time scientific mission performed at the company QUIPU, in Pisa, Italy, I had access to healthy volunteers data based on carotid ultrasound imaging and tonometry and brachial sphygmomanometry. The brachial diastolic pressure and mean arterial pressure were used as calibration values for carotid tonometric and ultrasound measurements. Models and signal processing were applied to the ultrasound signals in order to derive local estimation of blood pressure, which were analyzed bit-to-bit for various subjects. The tonometric device was employed as reference for comparison with the ultrasound measurements. I am confident that we can publish some interesting results from this STSM.

I am really grateful to all the members of QUIPU, and especially to Vincenzo Gemignani and Elisabetta Bianchini for their continuous support, great scientific knowledge and guidance to perform this extraordinary STSM experience. Also, thanks a lot to the COST Action CA18216 VascAgeNet to make this unique experience possible. I would definitely do it again.

I am Dr. Ryan John McNally, a pharmacist by background and now working as a postdoctoral research associate at King’s College London. Despite having developed and published systematic reviews and meta-analysis as first author, my analysis has been largely limited to mean differences in various continuous cardiovascular outcomes estimated in intervention studies.

I recently developed a collaboration with Professor Rosa Maria Bruno (Université Paris Cité, INSERM-PARCC, France) and Professor Ana Jerončić (University of Split, Croatia) to develop a systematic review and meta-analysis of the prognostic value of aortic pulse wave velocity in prediction of major cardiovascular disease events. We aspire to conduct this systematic review and metaanalysis with the aim to provide an overview of relevant studies and calculate robust quantitative estimates of the predictive value of arterial stiffness as expressed by aortic PWV for different outcomes such as total CV events (i.e., heart failure, stroke), CV mortality, and all-cause mortality.

The main objective of this STSM was to work with Professor Jerončić on the statistical meta-analysis of the data derived from this. This required a close collaboration for the curation of already extracted data from the literature, analysis of the data and in depth understanding of the statistical process involved and I aimed to learn about the complex statistical analysis and dataset structure set up that comes with harmonisation of data of this type.

Thanks to this STSM, I spent some time at the Medical Faculty of Split working with Professor Jerončić who has extensive experience in biostatistics and research methodology. With her guidance, I was able to learn the fundamental techniques and statistical methods required to perform the meta-analysis on data of this type whilst collaborating with her on the clinical implications of the statistical outcome. The opportunity of working in Split with Professor Jerončić allowed me to observe and learn from a different research environment which certainly helped promote the knowledge transfer (which would be difficult to achieve with only remote interactions) and was in line with the Action objectives.

On a more personal level, this STSM provided me the opportunity to refine my knowledge in statistical methods for large meta-analysis and the use of large population data in medical research. This close collaboration with Professor Jerončić also generated new ideas for research projects in the field of arterial stiffness and vascular aging. As an early career researcher, this STSM has supported my academic journey and assisted me to undergo the transition to become an independent investigator.

I am eternally grateful to VascAgeNet for this opportunity and to Professor Jerončić for her support.