Hidden Immune Cell Inflammation Drives Silent Heart Attack Risks

Linköping University Study Focuses on Dysregulated Neutrophils

According to research from Linköping University, immune cells known as neutrophils drive a silent inflammation that standard clinical tests fail to detect. This ongoing immune activity potentially elevates the risk of subsequent heart attacks. Coronary artery disease develops from plaque accumulating inside the arteries that supply blood to the heart. While the condition can remain stable for long stretches without causing symptoms, it can destabilize abruptly and trigger a heart attack. Following a cardiac event, low-grade inflammation often lingers for months or years. A broad body of research indicates that this persistent immune response raises the likelihood of another attack, a significant concern in Sweden where more than 20,000 people suffer a heart attack annually. Treatment options following a heart attack have advanced significantly through medications and balloon angioplasty. Despite these clinical improvements, the persistent inflammation that continues in these patients remains poorly understood, according to Lena Jonasson, professor of cardiology at Linköping University and consultant at Linköping University Hospital, who led the research. Researchers at the university concentrated their investigation on neutrophils, the most abundant immune cells in the human body. These cells must react swiftly to destroy bacteria and clear damaged cells. Previous studies demonstrated that neutrophils in patients with stable coronary artery disease activate too easily, reacting more strongly to stress than those found in healthy individuals. Furthermore, these cells appear in greater numbers in patients.

Cellular Mechanism and Regulatory T Cell Dysfunction

Normally, neutrophils circulate through the bloodstream for only 24 hours before undergoing programmed cell death, a tight regulation considered vital for ensuring that inflammation subsides when no longer required. To test whether this biological process breaks down in cardiovascular patients, the research team isolated neutrophils from the blood of 20 patients who had experienced a heart attack alongside 19 healthy individuals matched by age and sex. The patient cohort received optimal treatment under current guidelines, displayed no symptoms of coronary artery disease, and showed no signs of inflammation via the routine C-reactive protein test, known as CRP. During laboratory experiments, the team measured how neutrophils from both groups reacted and observed what happened when these cells were combined with regulatory T cells taken from the same individuals. Regulatory T cells normally suppress inflammation and control other immune cells by helping neutrophils die when functioning correctly. Maike Schneider, a doctoral student at Linköping University and the first author of the paper, explained the findings.

We showed that neutrophils in patients with stable coronary artery disease do not die as they should. They persist and remain highly active. We also found that regulatory T cells did not kill the patients’ neutrophils, unlike those from healthy individuals.

Maike Schneider These results demonstrate that dysregulated neutrophils may play a key role in the persistent low-grade inflammation observed in chronic coronary syndrome. According to the research team, relying solely on the standard CRP test provides limited insight because low CRP levels tell us very little. Identifying the underlying biological mechanisms is essential for improving diagnostics and developing new medicines.