Validation of a Digital Biomarker for Global Atherosclerosis - Project Summary/Abstract Peripheral artery disease (PAD) and coronary artery disease (CAD) are leading causes of morbidity and mortality worldwide, significantly increasing the risk of cardiovascular events, limb loss, and healthcare costs. Despite their impact, these conditions remain substantially underdiagnosed due to the limitations of conventional diagnostic methods. These methods require specialized equipment, trained personnel, and are often underutilized, resulting in critical gaps in early diagnosis and missed opportunities for intervention. This K23 proposal seeks to overcome these barriers by developing and validating novel, smartphone- based digital biomarkers for PAD and CAD using photoplethysmography (PPG), a non-invasive optical technology that can be seamlessly integrated into mobile devices and wearables. This approach aims to transform early vascular disease detection by providing a scalable, patient-centered solution that can be deployed at scale, aligning directly with the NHLBI’s mission to reduce the burden of cardiovascular disease and improve public health through innovative diagnostic technologies. The specific aims of this project are: Aim 1: Validate the diagnostic performance of a smartphone-based PAD digital biomarker against the gold- standard ABI. This prospective study (N=349) will assess the sensitivity, specificity, and area-under-the-curve (AUC) of the digital biomarker. Aim 2: Assess the diagnostic performance of the PAD digital biomarker for detecting CAD against the gold- standard CAC Agatston score. This prospective study (N=392) will evaluate the biomarker’s ability to detect coronary atherosclerosis. Aim 3: Evaluate the usability, feasibility, and acceptability of a smartphone-based PPG application for vascular screening in clinical settings. We will apply a two-phase mixed-methods approach grounded in human- centered design and implementation science frameworks. The objective of this aim is to evaluate the usability, feasibility, and acceptability of a smartphone-based PPG application for vascular screening in diverse clinical settings. This research will be conducted at the University of California, San Diego (UCSD), a leader in digital health innovation and translational science. UCSD provides robust research support through the Altman Clinical and Translational Research Institute (ACTRI), the UCSD School of Engineering and Design Lab, and partnerships with industry leaders, offering critical infrastructure for secure data processing and AI. The mentorship team includes Dr. Shamim Nemati, Dr. Elsie Ross, Dr. Pam Taub. This multidisciplinary team, alongside the collaborators, provides critical guidance in machine learning, artificial intelligence, biostatistics, clinical trial design, regulatory science, and digital health innovation, ensuring a successful transition to independence as an R01-funded physician-scientist.
