A Novel Mechanism Links Lipoprotein(a) to Blood Clotting in the Arteries and Increased Risk of Heart Attack
Mount Sinai-led study leads to improved understanding of risk
Journal: Journal of Lipid Research – May 2025
https://www.jlr.org/article/S0022-2275(25)00080-X/fulltext
Author: Robert S. Rosenson, MD, Director of Metabolism and Lipids at the Icahn School of Medicine of Mount Sinai
Bottom line of study: High lipoprotein(a) or Lp(a) in patients with coronary artery disease carry and express more tissue factor (the key regulator of blood clotting from the arterial wall) on their monocytes and express more tissue factor on their monocytes. The tissue factor in patients with high Lp(a) activates blood clotting, which can lead to a heart attack.
Why the study is unique? This is the first study to demonstrate a link between inflammation from circulating monocytes and tissue factor production, expression, and function.
Why the study is important? Many patients with high Lp(a) levels have an acute myocardial infarction as the first manifestation of cardiovascular disease. This is a thrombotic event that has been attributed incorrectly to impaired clot dissolution by apolipoprotein – apo(a). However, those studies separated the apo(a) from the intact molecule and may not have relevance. Further, patients with high Lp(a) do not have higher rates of venous clots in the legs or pulmonary emboli.
How was the research conducted? Researchers performed proteomic, transcriptomic, and functional biology studies on blood collected from 64 patients with coronary artery disease.
Results: High versus low Lp(a) levels were associated with significantly elevated markers of inflammation and vascular dysfunction. One of these vascular markers was tissue factor present on the circulating monocytes, a type of white blood cells that enter the arterial wall and participated in plaque formation. The mononuclear cells of patients with high Lp(a) levels also expressed more tissue factor through a specific receptor-mediated pathway. Importantly, the tissue factor was functional in that it accelerated the conversion of protein Factor X to Factor Xa, an activated clotting factor that promotes blood clotting.
What the study means for patients? This study provides insights into the reason that many patients have an acute myocardial infarction as their first manifestation of cardiovascular disease. The importance of the tissue factor pathway may allow for better refinement of cardiovascular risk in patients with high Lp(a).
What the study means for clinicians? This study provides insights into the basis for the arterial thrombi or blood clots that occur in patients with high Lp(a), and provides a framework for studies to more completely and accurately identify the highest risk patients.
Project Co-principal investigator: Sascha N. Goonewardena, MD, Division of Cardiovascular Medicine, University of Michigan
Quotes:
“This newly defined mechanism contributes to a better understanding of blood clotting in coronary heart disease patients,” says Dr. Rosenson. “Linking Lp(a) to immune-mediated blood clotting enhances understanding of high-risk status for patients with high Lp(a) and can better inform clinical trial design and study populations to account for risk associated with Lp(a) and tissue factor to help save lives.”
Mount Sinai Is a World Leader in Cardiology and Heart Surgery
Mount Sinai Fuster Heart Hospital at The Mount Sinai Hospital ranks No. 4 nationally for cardiology, heart, and vascular surgery, according to U.S. News & World Report®. It also ranks No. 1 in New York and No. 6 globally according to Newsweek’s “The World’s Best Specialized Hospitals.”
It is part of Mount Sinai Health System, which is New York City's largest academic medical system, encompassing seven hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. We advance medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 9,000 primary and specialty care physicians; 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 45 multidisciplinary research, educational, and clinical institutes. Hospitals within the Health System are consistently ranked by Newsweek’s® “The World’s Best Smart 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's® “Best Hospitals” Honor Roll for 2024-2025.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Instagram, LinkedIn, X, and YouTube.
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.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Instagram, LinkedIn, X, and YouTube.