Abstract
Cardiovascular diseases (CVDs) remain the leading cause of global mortality, therefore understanding arterial stiffness is essential to develo** innovative technologies to detect, monitor and treat them. The ubiquitous spread of photoplethysmography (PPG), a completely non-invasive blood-volume sensing technology suitable for all ages, highlights immense potential for arterial stiffness assessment in the wider healthcare setting outside specialist clinics, for example during routine visits to a General Practitioner or even at home with the use of mobile and wearable health devices. This study employs a custom-manufactured in vitro cardiovascular system with vessels of varying stiffness to test the hypothesis that PPG signals may be used to detect and assess the level of arterial stiffness under controlled conditions. Analysis of various morphological features demonstrated significant (p < 0.05) correlations with vessel stiffness. Particularly, area related features were closely linked to stiffness in red PPG signals, while for infrared PPG signals the most correlated features were related to pulse-width. This study demonstrates the utility of custom vessels and in vitro investigations to work towards non-invasive cardiovascular assessment using PPG, a valuable tool with applications in clinical healthcare, wearable health devices and beyond.
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Introduction
Cardiovascular diseases (CVD) stand as the leading contributor to global mortality1,2,3. Within the spectrum of CVD are diseases impacting both the heart and blood vessels. Examples include coronary artery disease (CAD), heart attack, stroke, and even the ageing of the vascular system, which profoundly influences heart and vessel health. Considering the inevitable nature of vascular ageing, it becomes crucial to delve into this domain and introduce innovative approaches for evaluating the ageing process of blood vessels.
The term "vascular ageing" describes the alterations that take place in the blood vessels with age, such as a loss of elasticity, which can impair the vascular system's ability to operate efficiently. Arterial stiffness results from the arteries loss of elasticity, and this is an important indicator of vascular ageing4. Understanding the connection between vascular ageing and arterial stiffness will help better understand age-related disorders.
Photoplethysmography (PPG), an established optical sensing method, has enormous promise for assessing cardiovascular health5,6,7,5, the reliable features can be determined. According to the boxplots, the most stable features are those related to area, amplitude, and width, as well as indexes such as skewness, kurtosis, and signal-to-noise ratio show notable change between stiffnesses while maintaining a low variation at each vessel. This suggests that these features can be used in a wide range of applications for non-invasive measurement, as low variability and high correlation would result in reliable arterial stiffness assessment, and possible other factors such as blood pressure. This hypothesis must be followed up with patient studies to compare pulse feature reliability in vivo. These results also showcase the value of signal indexes, for example pulse skewness and kurtosis, as they can be correlated with physiological phenomena such as vascular stiffening more strongly than some geometrical features44,45. These indexes can be used alongside geometrical features to better predict cardiovascular diseases.
Box plots showing change in red and infrared PPG features with each of the custom vessels, in order of increasing arterial stiffness.
A ranking based on correlation coefficients can signify the most reliable PPG features for arterial stiffness measurement, which can also be employed in in vivo and in vitro studies. As shown in Fig. 6, there is a significant link between arterial stiffness and the area of the PPG wave, as the three highest correlated features in red PPGs are areas under the curve. Interestingly, these features are not as highly ranked in infrared signals, further demonstrating the versatility of multi-wavelength measurement. The top three infrared PPG features are width related, suggesting that PPG wavelengths are affected differently by physiological changes such as arterial stiffness. To further discern the morphological differences, it is worth conducting investigations utilising other commonly used PPG wavelengths such as green light.
Red and infrared PPG features ranked by Pearson correlation coefficient with arterial stiffness. Only features which have a correlation coefficient with a corresponding p-value < 0.05 (statistically significant at 5% level) are displayed. (Green bars indicate positive correlation and purple bars indicate negative correlation).
Conclusion
This study has successfully demonstrated the use of PPG feature extraction and significance testing to identify morphological features affected by vessel stiffness in an in vitro environment. PPG signals were recorded from a range of vessels, resembling various stages of healthy and diseased arteries, which revealed distinct morphological changes correlated to arterial stiffness. Notably, red PPG signals showed the greatest shifts in area-related features, while pulse width infrared features were more strongly associated with arterial stiffness changes. This work expands the scope of non-invasive arterial stiffness evaluation and paves the way for further research involving more rigorous in vitro experiments, such as analysis at varying heart rates and flow rates to determine differences in responsiveness to flow changes between stiffnesses; as well as parallel in vivo studies to unravel the impact of biological factors such as age and respiration on PPG pulse shape.
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Conducting experiments and data analysis—R.F. and P.K.; Writing—R.F. and P.K.; Review and editing—J.M.M. and P.A.K.; Supervision—J.M.M. and P.A.K.
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Ferizoli, R., Karimpour, P., May, J.M. et al. Arterial stiffness assessment using PPG feature extraction and significance testing in an in vitro cardiovascular system. Sci Rep 14, 2024 (2024). https://doi.org/10.1038/s41598-024-51395-y
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DOI: https://doi.org/10.1038/s41598-024-51395-y
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