Immune marker suPAR high in patients with heart failure

The ability to predict risk was even greater when combined with traditional measures of cardiac stress.


Cardiologists have long relied on a hormone called BNP as the gold standard to assess the risk of serious illness or death in patients with heart failure. The heart releases it in response when the cardiac tissue extends due to pressure.

B-type natriuretic peptide, or BNP, is a “downstream” sign of heart failure. Still, scientists are searching for biomarkers focused on what causes heart failure, such as myocardial injury or inflammation.

According to a recent study from Michigan Medicine and the Emory Clinical Cardiovascular Research Institute, patients with heart failure had high levels of the immunological protein suPAR, which is known to play a role in kidney disease and can predict both heart failure and death. Beyond that, the ability to anticipate such risk is further enhanced when suPAR and BNP are combined.

Salim Hayek, M.D., an assistant professor of internal medicine and medical director of the University of Michigan Health Frankel Cardiovascular Center clinics, said, “Several markers have been examined for heart failure and its adverse outcomes, but few have ever shown to be additive to BNP, or sometimes better than BNP, which is what we find here. BNP is a marker that varies dramatically depending on the patient’s fluid status. A more stable marker, such as suPAR linked to the pathophysiology of heart failure, could be more useful in identifying patients at higher, long-term risk of disease progression or death.”

Scientists used the Emory cardiovascular biobank to measure plasma suPAR and BNP levels in over 3,400 participants undergoing heart imaging, following them for more than six years.

According to the findings, suPAR levels were 17% greater in heart failure patients than those without the condition in all subgroups, including those with ischemic or non-ischemic cardiomyopathy. The chance of dying from any cause, cardiovascular disease, and being hospitalized for heart failure increased by more than two times with protein levels.

Also, with increased SuPAR in patients without heart failure, they were over 3.5 times more likely to develop the condition.

Hayek said, “We see that suPAR has a major role in cardiovascular disease as a marker of immune activation, which likely reflects an upstream process of stress and inflammation that can cause heart failure. SuPAR is also known to cause kidney disease – an important component of the pathophysiology of heart failure. This may explain why suPAR levels strongly predict long-term outcomes in these patients.”

“A growing body of research links suPAR and poor outcomes for various conditions, from coronary artery disease to cancer and kidney dysfunction. The common disease pathway in these conditions is persistent immune system activation, which is reflected in high suPAR levels.”

Senior author Arshed Ali Quyyumi, M.D., FACC, Director of the Emory Clinical Cardiovascular Institute and professor of medicine in the Division of Cardiology at Emory University School of Medicine said“On the practical side, there is a potential for suPAR to be among the biomarkers that we measure to create a strategy for personalizing care for individual patients. For example, we could use it to differentiate between admitted patients at low and high risk of worsening heart failure. Then we could better allocate post-discharge resources to those at higher risk, which would lessen the cost burden of managing the disease. There are many potential opportunities to use suPAR to improve care.”

Journal Reference:

  1. Salim S. Hayek et al. Soluble Urokinase Plasminogen Activator Receptor Levels and Outcomes in Patients with Heart Failure. Journal of Cardiac Failure. DOI: 10.1016/j.cardfail.2022.08.010