Title: Continuous monitoring of vascular age by pulse wave velocity using wearable ECG and PPG sensors
Funder: Economic and Social Research Council

Abstract: BACKGROUND/PROBLEM While healthy ageing is one of the most important challenges of our time, there are no accessible biomarkers available. The continuous measurement of an accessible physiological biomarker of ageing using low-cost methodology would form the basis of future efforts to understand human ageing better and, more importantly, allow the testing and implementation of interventions that target human ageing at scale and during everyday life. Human ageing leads to progressive stiffening of the arteries which is the results of many injurious events that occur during everyday life and currently go undetected. Arterial stiffness can be measured non-invasively as pulse wave velocity (PWV) and is viewed as the most important biomarker of vascular age, but it currently requires costly and bulky research equipment. However, personal devices are now able to measure a variety of biological information including blood flow (PPG=photoplethysmography) and electrical activity of the heart (ECG=electrocardiogram). This information can be used to calculate PWV with each heartbeat in real time and provide immediate information on the biological age of the blood vessels. So far, no technology is available that fulfils this task. OBJECTIVES To develop low-cost technology using existing devices or new prototype device build with available components to allow monitoring of vascular age at scale and during everyday life. 1. Set-up developmental sensing tools to integrate data from sensors to continuously calculate and visualize PWV We will start with the development of the sensing tools to continuously monitor the blood volume changes with PPG sensors and electric activity of the heart (ECG) at the same time using multiple sensors. With these data, PWV and an estimate of blood pressure will be calculated with each heart beat. We will optimize the PPG signals by varying the positions of sensors to optimise signals,integrate the measurements, identify important determinants of the signals by parallel application of other sensors that measure physiological functions including blood pressure, motion and environmental data with machine learning, and visualize and quantify the changes in waveform shape data online using a recently developed mathematical method by Prof. Aston. 2. Accuracy, validation, and variability of continuous PWV measurements It is the aim of this study to determine (a) the accuracy of development set-up to determine PWV in key groups of people under resting conditions (supine, sitting, standing) and walking, (b) validate set-up to show significant changes of PWV across healthy ageing people and in people with vascular disease, and (c) intra- and inter-individual variability to evaluate reproducibility. We will perform repeated measurements in healthy humans of different ages and people with vascular disease. Measurements will be performed side by side with an established arterial tonometry and blood pressure measurements to clinically validate absolute values and dynamic response in relationship to these gold standard measurements. Machine learning will be applied to improve accuracy and reproducibility. 3. Evaluation of existing low-cost devices and draft prototype device build from standard sensor components for continuous monitoring of PWV over time Based on the results obtained with our development set-up kit in (1.&2.), we will draft an aspirational prototype device design taking available low cost standard ECG and PPG components into account. We will also review and summarize the technical capabilities, design, and price of wearable devices that are technically capable of performing simultaneous ECG and PPG recording currently on the market. The outcome of this analysis will determine the focus the second phase (next funding period): designing a very low-cost prototype device (by Surrey Sensors Ltd.) or/and developing a PWV software solution for fitness wristbands already on the market.

Lay abstract: BACKGROUND While healthy ageing is one of the most important challenges of our time, it is difficult to monitor ageing during normal life. Longterm vascular ageing is the results of many injurious events that occur during everyday life and currently go undetected. The ability to continuously measure ageing with low cost devices would open opportunities to test interventions that aim to slow ageing in a large number of individual people. Progressive stiffening of the blood vessels is one of the most important features of human ageing. Importantly, arterial stiffness can be measured non-invasively as pulse wave velocity (PWV) and is viewed as the most important biomarker of vascular age, but it currently requires costly and bulky equipment and trained researchers to measure. However, personal devices like fitness bracelets and smart watches are now able to measure a variety of biological information including blood flow and electrical activity of the heart. This information could be used to calculate PWV with each heartbeat in real time and provide immediate information on the biological age of the blood vessels. More importantly, this approach would allow the identification of factors that accelerate and slow ageing in an individual person and monitor the success of 'anti-ageing' therapies in an individual person. So far, no technology is available that fulfils this task. OBJECTIVES OF PROPOSED RESEARCH In the current project, we wish to develop low-cost methods to allow monitoring of individual 'vascular age' at scale during real life using wearables or design a prototype device with available components. In this first phase of the project, we will set up a developmental tool kit to integrate data from ECG (electrocardiogram, electrical activity of the heart) and PPG (photoplethysmography, blood flow in the skin) sensors, calculate PWV, and create useful visualization of integrated data. We will then test the accuracy, validity, and performance of PWV measurements in people at different age and with vascular disease under different conditions and compare the results with gold standard methods (tonometry) to measure PWV. Furthermore, we will design a prototype device build from low-cost standard sensor components (by Surrey Sensors Ltd.) and evaluate if existing low-cost devices can be used for continuous monitoring of PWV over time to help us decide on the focus of the next steps. FUTURE DIRECTION Reaching these objectives will form the basis of moving forward with a second application next year. In this second step, we will build a small number of prototype devices to and/or develop a software solution for using sensor data from existing fitness devices for continuous PWV measurements. We will then test the utility and applicability of continuous PWV in real life in people of different ages to establish normal values. Furthermore, we hope to validate the measurements by comparing results with invasively measured PWV during routine catheter procedures in the hospital. In a third step, we plan to perform a proof-of-concept study to demonstrate the abilities of continuous PWV measurements to detect acute responses of arterial stiffness to life-style interventions such as healthy diet and chronic changes in arterial stiffening over time (vascular ageing trajectory). In a future stage, we hope to be able to test the continuous PWV measurements in larger groups of people, potentially in collaboration with industry, NHS, and using sensor data from devices that people already own. Large data sets can then be analysed together with other individual health related data by machine learning to identify ageing patterns and effect of healthcare interventions on trajectories of vascular ageing.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR