U of M researchers find connection between blood protein and increased heart failure risk

MINNEAPOLIS/ST. PAUL (12/05/2024) — Published in Circulation, new research led by a University of Minnesota Medical School research team found a connection between a lower level of factor XI — a protein that helps with blood clotting which is targeted by new blood thinners — and an increased risk of heart failure. 

Anticoagulants, commonly known as blood thinners, are medications used to prevent blood clots and strokes in patients with atrial fibrillation, an irregular rhythm that begins in the upper chambers of the heart. Researchers are exploring a new type of blood thinners called factor XI inhibitors, which may be associated with a lower risk of bleeding than current blood thinners. Preclinical model studies have shown that factor XI may protect the heart from fibrosis, heart failure and abnormal heart rhythms, including atrial fibrillation. Until now, no human evidence has linked lower levels of factor XI to heart failure or atrial fibrillation.

In this study involving two large community-based cohorts, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), researchers found that a lower factor XI level was associated with a higher risk of developing heart failure. In addition, ARIC participants with lower factor XI levels showed a greater likelihood of atrial fibrillation and worse heart function. 

"Based on the findings of this research, doctors and scientists should be mindful of potential side effects as researchers develop factor XI inhibitors as a new class of blood thinners,” said Lin Yee Chen, MD, MS, a professor and director of the Lillehei Heart Institute at the U of M Medical School, and senior author of the study. “It is important to note that our findings do not imply causation; thus, more research is needed to assess potential causal relationships between factor XI inhibition and adverse cardiovascular events.”

Future research should also focus on understanding how lower factor XI level contributes to a higher risk of heart failure. 

Funding was provided by the National Institutes of Health.

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Grant award numbers include HL0597367, R01HL141288, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, U01HL130114; contract Nos. 75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005, HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and 75N92021D00006.

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