Digital Marker for Coronary Artery Disease Built by Researchers at Mount Sinai
Machine learning-derived model could lead to better disease screening, diagnostics, and management
Using machine learning and clinical data from electronic health records, researchers at the Icahn School of Medicine at Mount Sinai in New York constructed an in silico, or computer-derived, marker for coronary artery disease (CAD) to better measure clinically important characterizations of the disease.
The findings, published online on December 20 in The Lancet, may lead to more targeted diagnosis and better disease management of CAD, the most common type of heart disease and a leading cause of death worldwide. The study is the first known research to map characteristics of CAD on a spectrum. Previous studies have focused only on whether or not a patient has CAD.
CAD and other common conditions exist on a spectrum of disease; each individual’s mix of risk factors and disease processes determines where they fall on the spectrum. However, most such studies break this disease spectrum into rigid classes of case (patient has disease) or control (patient does not have disease). This may result in missed diagnoses, inappropriate management, and poorer clinical outcomes, say the investigators.
Caption: Individuals with coronary artery disease exist on a spectrum of disease, such as the amount of plaque build-up in the arteries of the heart; however, the disease is conventionally classified as broad categories of case (yes disease) or control (no disease), which may result in misdiagnosis. A digital marker for coronary artery disease derived from machine learning and electronic health records can better quantify where an individual falls on the disease spectrum.
Credit: Icahn School of Medicine at Mount Sinai
“The information gained from this non-invasive staging of disease could empower clinicians by more accurately assessing patient status and, therefore, inform the development of more targeted treatment plans,” says Ron Do, PhD, senior study author and the Charles Bronfman Professor in Personalized Medicine at the Icahn School of Medicine at Mount Sinai.
“Our model delineates coronary artery disease patient populations on a disease spectrum; this could provide more insights into disease progression and how those affected will respond to treatment. Having the ability to reveal distinct gradations of disease risk, atherosclerosis, and survival, for example, which may otherwise be missed with a conventional binary framework, is critical.”
In the retrospective study, the researchers trained the machine learning model, named in silico score for coronary artery disease or ISCAD, to accurately measure CAD on a spectrum using more than 80,000 electronic health records from two large health system-based biobanks, the BioMe Biobank at the Mount Sinai Health System and the UK Biobank.
The model, which the researchers termed a “digital marker,” incorporated hundreds of different clinical features from the electronic health record, including vital signs, laboratory test results, medications, symptoms, and diagnoses, and compared it to both an existing clinical score for CAD, which uses only a small number of predetermined features, and a genetic score for CAD.
The 95,935 participants included participants of African, Hispanic/Latino, Asian, and European ethnicities, as well as a large share of women. Most clinical and machine learning studies on CAD have focused on white European ethnicity.
The investigators found that the probabilities from the model accurately tracked the degree of narrowing of coronary arteries (coronary stenosis), mortality, and complications such as heart attack.
“Machine learning models like this could also benefit the health care industry at large by designing clinical trials based on appropriate patient stratification. It may also lead to more efficient data-driven individualized therapeutic strategies,” says lead author Iain S. Forrest, PhD, a postdoctoral fellow in the lab of Dr. Do and an MD/PhD student in the Medical Scientist Training Program at Icahn Mount Sinai. “Despite this progress, it is important to remember that physician and procedure-based diagnosis and management of coronary artery disease are not replaced by artificial intelligence, but rather potentially supported by ISCAD as another powerful tool in the clinician’s toolbox.”
Next, the investigators envision conducting a prospective large-scale study to further validate the clinical utility and actionability of ISCAD, including in other populations. They also plan to assess a more portable version of the model that can be used universally across health systems.
The paper is titled “Machine learning-based marker for coronary artery disease: derivation and validation in two longitudinal cohorts.” Additional co-authors are Ben O. Petrazzini, BS, Áine Duffy, MS, Joshua K. Park, BS, Carla Marquez-Luna, PhD, Daniel M. Jordan, PhD, Ghislain Rocheleau, PhD, Judy H. Cho, MD, Robert S. Rosenson, MD, and Jagat Narula MD, and Girish N. Nadkarni, MD.
The work was supported by funds from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) grants T32-GM007280 and R35-GM124836, and by the National Heart, Lung, and Blood Institute of the NIH grants R01-HL139865 and R01-HL155915.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 560 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
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