Inflammation is emerging as a major target in the search for better treatments for the artery-clogging disease that causes heart attacks and strokes.

Atherosclerosis has traditionally been viewed largely as a cholesterol problem. But researchers now have a clearer picture of another force driving the disease: chronic inflammation.

Atherosclerosis occurs when fatty deposits, cholesterol and other substances accumulate inside artery walls, forming plaques. As these plaques develop, the body’s immune system responds. Immune cells called macrophages move into the affected area and attempt to remove excess cholesterol and repair damaged tissue.

The problem is that these cells can eventually become overwhelmed.

Excess cholesterol and toxic cholesterol byproducts can impair macrophages, while ongoing inflammation makes it harder for them to perform their protective functions. Some macrophages eventually die, adding material to the plaque and potentially making it larger and more unstable.

Inflammation can also affect neighboring cells in the artery wall, further contributing to plaque development.

A new treatment strategy

This understanding has led scientists to investigate whether controlling inflammation could help prevent heart attacks and strokes.

Clinical studies have already provided evidence that reducing inflammation can lower cardiovascular risk independently of lowering cholesterol. Drugs such as canakinumab and colchicine have demonstrated the potential of this approach.

However, the results so far have generally been modest. Researchers say this may indicate that the key inflammatory pathways have not yet been targeted precisely enough.

A recent review, Targeting Inflammation in Atherosclerosis: Mechanistic Rationale, Clinical Trials, and

Regulatory Considerations, examines the growing evidence and the next generation of possible treatments.

Among the pathways receiving attention is the NLRP3 inflammasome, a molecular system that can trigger production of inflammatory signals including IL-1β and IL-6. These signals can intensify inflammation and contribute to plaque growth and instability.

Scientists are now investigating treatments that specifically target IL-6, selective NLRP3 inhibitors and other emerging approaches, including cell-based therapies.

Finding the right patients

One of the biggest challenges is determining who has significant inflammation inside their arteries and is most likely to benefit from an anti-inflammatory treatment.

Blood tests measuring markers such as high-sensitivity C-reactive protein (hsCRP) and IL-6 can provide clues, but researchers are looking for more sensitive and specific biomarkers.

The liver is also attracting attention because of its role in connecting inflammation with the body’s blood-clotting systems. Understanding this relationship could eventually help researchers develop new ways to identify people at high cardiovascular risk.

The road ahead

Anti-inflammatory treatments are not without challenges. Some can increase the risk of infections, while biological therapies can be expensive. Researchers also need better methods for selecting patients and stronger evidence that new treatments can prevent major events such as heart attacks and strokes.

For now, cholesterol reduction remains a cornerstone of atherosclerosis treatment. But scientists increasingly view the disease as more than a buildup of cholesterol.

By understanding and potentially controlling the inflammation that helps drive plaque formation and instability, researchers hope to develop more precise treatments that could do more than simply slow the disease.