Mapping of Atherosclerotic Plaque Cells Predicts Future Risk of Stroke or Heart Attack

Atherosclerosis is the leading cause of cardiovascular diseases like heart attacks and strokes. Over many years, atherosclerotic plaques develop from the accumulation of blood lipids such as cholesterol in the innermost layer of blood vessels. As these plaques become unstable and rupture, blood clots can form, blocking the vessel or traveling to other organs, like the brain. This blockage prevents oxygen from reaching the tissues, leading to a stroke or heart attack. Mortality rates from cardiovascular disease have decreased over the past 50 years due to advancements in understanding disease mechanisms, improved preventive treatments, better diagnostics, and healthier lifestyle choices. Now, a new study has revealed that genetic traits play a role in determining the cellular makeup of atherosclerotic plaques, which influences the likelihood of these plaques causing strokes or heart attacks over time. This discovery could enhance future risk assessment and treatment strategies for patients with atherosclerosis.

Researchers at Karolinska Institutet (Stockholm, Sweden), along with colleagues, successfully mapped the relationship between genetic factors and the composition of different cell types in atherosclerotic plaques. Their research, published in the European Heart Journal, utilized tissue samples from patients with atherosclerosis, stored in a biobank. The researchers used this genetic data to categorize patients into three distinct groups. The first group, with the most severe profiles, typically includes patients who have already experienced a stroke. The second group consists of patients at lower risk, whose vessels contain plaques but have not resulted in a stroke. The third group falls between the other two and often has kidney disease alongside atherosclerosis.

Image: Patients can be divided into three groups with different disease severity based on composition of smooth muscle cells in blood vessels (Photo courtesy of Melody Chemaly)

The team has also found preliminary evidence suggesting that this genetic influence might apply to heart attacks as well. This new understanding of how genetics affect plaque cell composition could be integrated with advanced diagnostic imaging and AI to improve assessments of future stroke or heart attack risks and predict how patients might respond to different treatments. While the researchers have conducted similar studies for smaller cohorts in the past, this concept needs to be validated on a larger scale before it can be used in clinical practice. The team plans to continue working on these multi-modal studies to further develop this approach.

“Previous research has shown that heredity is important for the levels of cholesterol, other lipids and circulating immune cells in the blood, but now we see that heredity also affects the composition of smooth muscle cells in the blood vessels of atherosclerotic patients,” says Ljubica Matic, docent at the Department of Molecular Medicine and Surgery at Karolinska Institutet who led the study. “This can affect the development of atherosclerotic plaques, but also the tendency for the plaques to become unstable and cause a stroke.”