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Antibodies associated with rare disorder may signal future risk of heart attack and stroke

UTSW study suggests lab tests might one day be used as a new way to predict cardiovascular disease

DALLAS – May 15, 2023 – Seemingly healthy people whose blood contained antibodies associated with a condition called antiphospholipid syndrome (APS) were significantly more likely to experience a cardiovascular event such as a heart attack or stroke than those without, a study led by UT Southwestern Medical Center scientists shows. The findings, published in JAMA Network Open, suggest a new way to predict cardiovascular disease risk.

James de Lemos, M.D.
James de Lemos, M.D., is Professor of Internal Medicine and Chief of the Division of Cardiology at UT Southwestern and holds the Sweetheart Ball – Kern Wildenthal M.D., Ph.D., Distinguished Chair in Cardiology.

“APS itself is rare, but some people in the general population who have never been diagnosed with APS may carry its antibodies. This study is a first look at whether there might be a broader role of testing for these antibodies,” said James de Lemos, M.D., Professor of Internal Medicine and Chief of the Division of Cardiology at UT Southwestern. Dr. de Lemos co-led the study with Yu (Ray) Zuo, M.D., MSCS,  a former faculty member in the Division of Rheumatic Diseases at UTSW who is now the Edward T. and Ellen K. Dryer Early Career Professor of Rheumatology and Assistant Professor at the University of Michigan School of Medicine.

APS is an autoimmune disease in which antibodies target cells that line blood vessels, platelets, and immune cells, encouraging the formation of blood clots that can lead to heart attacks, strokes, or deep vein thrombosis, and can contribute to pregnancy loss. APS is typically diagnosed by testing for antiphospholipid antibodies only after individuals experience a serious clotting event or have recurrent miscarriages, Dr. de Lemos explained. However, previous research has shown that a significant number of people who have not had clot-related cardiovascular problems also carry antiphospholipid antibodies. Whether these antibodies play a role in cardiovascular disease or how has been unclear.

To help answer those questions, Dr. de Lemos and his colleagues turned to the Dallas Heart Study, which was started in 2000 and produces data on cardiovascular disease risk from thousands of participants. Dr. de Lemos currently serves as the study’s Principal Investigator.

The research team tested blood that had been collected from study participants between 2007 and 2009 and looked for the presence and amounts of eight different antiphospholipid antibodies. They analyzed these data along with questionnaire responses gathered during a follow-up period that averaged eight years to see which participants experienced a heart attack, stroke, coronary bypass surgery, or death from cardiovascular disease.

The researchers detected antiphospholipid antibodies in about 14.5% of the 2,427 study participants. About a third of those had antibody levels that were considered moderate or high. Over the follow-up period, 125 individuals experienced cardiovascular events. After adjusting for risk factors such as age, sex, race, body mass index, smoking history, cholesterol levels, and diabetes, the researchers found that the presence of two particular antiphospholipid antibodies – aCL IgA and ab2GPI IgA – was associated with a future cardiovascular event. In participants with relatively higher levels of these two antibodies, this connection was even stronger.

Lab tests suggested that these antibodies could impair the ability of “good” cholesterol to absorb lipids in the blood and ferry them to the liver for disposal. They may also encourage the formation of atherosclerotic plaques in the heart, brain, and elsewhere.

Dr. de Lemos noted that because antibody levels can be transient and blood samples were done on a single visit, more studies are needed to better understand whether antiphospholipid antibodies remain elevated in people without diagnosed APS and how this might relate to heart disease.

Ravi Sarode, M.D.
Ravi Sarode, M.D., is Chief of Pathology at UT Southwestern and holds the John H. Childers, M.D. Professorship in Pathology.

Ravi Sarode, M.D., Chief of Pathology at UT Southwestern, said that if further research supports the study’s initial findings, labs would be able to test patients for antiphospholipid antibodies.

“These antibodies are easy to test; we test them all the time in our lab for certain patients,” said Dr. Sarode, Professor of Pathology and Internal Medicine in the Division of Hematology and Oncology and Medical Director of Clinical Laboratory Services and the Division of Transfusion Medicine and Hemostasis at UT Southwestern. “It is very important to note that very few labs test for these specific antibodies. However, we would need more information to use them in the right clinical setting for patients who may be at higher risk of heart attack or stroke.”

Other UTSW researchers who participated in this study include faculty members in Internal Medicine: Colby R. Ayers, M.S.E., Faculty Associate; Blair Solow, M.D., Associate Professor; Bonnie Bermas, M.D., Professor; Anand Rohatgi, M.D., Professor; and David R. Karp, M.D., Ph.D., Professor and Chief of the Division of Rheumatic Diseases.

Dr. de Lemos holds the Sweetheart Ball – Kern Wildenthal M.D., Ph.D., Distinguished Chair in Cardiology. Dr. Sarode holds the John H. Childers, M.D. Professorship in Pathology.

This study was financed with a Pfizer Aspire Award. The Dallas Heart Study was initially funded by grants from the Donald W. Reynolds Foundation and is now supported by The Hoffman Family Center in Genetics and Epidemiology and the National Center for Advancing Translational Sciences (UL1TR001105).

About UT Southwestern Medical Center  

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.

Latest research

The original Dallas Heart Study helped define novel biological variables that contribute to cardiovascular disease among various racial groups. Two decades later, with an aging and increasingly diverse population, the Dallas Heart and Minds Study is leveraging those initial findings and expanding their scope. The current phase focuses on a multiethnic population and emphasizes factors that promote healthy aging, characterized not only as the avoidance of disease but also the maintenance of cardiovascular health, high physical and cognitive function, and engagement with social activities.