Immune Checkpoint Inhibitors Linked to Increased Heart Disease Risk

A potent class of cancer therapies known as immune checkpoint inhibitors, designed to enhance the immune system’s ability to attack tumors, may increase the risk of heart attacks and strokes, according to a new study. Researchers at NYU Langone Health and its Perlmutter Cancer Center found that these treatments might interfere with immune regulation in major arteries, triggering inflammation in patients with cardiovascular risk factors.

Cancer Treatment’s Double-Edged Effect

Immune checkpoint inhibitors target molecules that act as immune "brake pedals," which ordinarily prevent excessive immune activity. By blocking these checkpoints, the therapy enables the immune system to attack cancer cells more aggressively. However, this heightened immune response can inadvertently provoke damaging inflammation in organs such as the heart, brain, and stomach.

Past studies have shown that approximately 10% of patients with atherosclerosis—characterized by hardened plaques in artery walls—experience a heart attack or stroke following treatment with these therapies. While the cardiovascular side effects were previously noted, the underlying mechanisms remained unclear.

The new study, published in Nature Cardiovascular Research, demonstrates that the immune checkpoints targeted by these cancer therapies are also present in immune cells within arterial plaques. Genetic analyses revealed that blocking these checkpoints increases inflammation, linking checkpoint inhibitors to heightened cardiovascular risks.

The Overlap of Cancer, Diabetes, and Heart Disease

The research emphasizes the interconnected nature of cancer, diabetes, and cardiovascular disease. “Cancer patients and their physicians should be aware that they may need to monitor for new heart concerns following cancer treatment,” explained co-senior author Chiara Giannarelli, MD, PhD.

The study also explored how type 2 diabetes—a common risk factor for both cancer and cardiovascular disease—exacerbates the cardiovascular side effects of checkpoint inhibitors. Tissue analysis from patients with diabetes revealed reduced communication between immune checkpoints in arterial cells, potentially increasing inflammation and plaque buildup.

Dietary Challenges in Therapy

Further experiments in rodent models showed that immune checkpoint inhibitors could counteract the anti-inflammatory benefits of a low-fat diet, which is commonly prescribed to manage atherosclerosis. While such diets typically reduce plaque buildup by boosting immune checkpoint activity, these therapies interfere with this effect, complicating efforts to mitigate cardiovascular risks for cancer patients.

Toward Safer Cancer Care

The study underscores the importance of considering how cancer treatments impact other health conditions. “Now that experts have a better understanding of the interplay between these diseases, they can begin to explore new strategies to lower the risk of unintended health concerns caused by their treatment,” noted Kathryn Moore, PhD, the study’s co-senior author.

While these findings provide critical insights, the researchers caution that their analysis did not directly assess checkpoint behavior in cancer patients. Future clinical studies will be essential to confirm these findings and develop interdisciplinary care strategies for individuals with cancer and cardiovascular risk factors.