By analyzing large amounts of data, researchers at Karolinska Institutet have developed a system for classifying individuals into different risk groups for atherosclerosis. The results enable early detection of the disease, which can lead to personalized preventive care.
Atherosclerosis is a silent disease that often only becomes apparent when a cardiovascular event occurs. If we can identify individuals at risk of atherosclerosis progression before symptoms occur, it may be possible to intervene, halt progression and prevent serious conditions such as heart attack or stroke.
In the new study, researchers used extensive data from three large cohorts in Europe: SCAPIS, UK Biobank, and IMPROVE. The researchers discovered that it is possible to distinguish four different risk groups of individuals, whose susceptibility for heart attacks and strokes could be graded from low to very high.
The researchers were also able to identify the genes that drive the risk of cardiovascular events in each group. In particular, they identified a specific genetic variant in the IL6R gene, which is involved in the regulation of inflammation in atherosclerosis. This variant has a modest effect on the risk of cardiovascular events in the general population, but it amplified the risk of heart attack only in the group of individuals with a very high predicted risk of cardiovascular events. Identifying such a gene is the first step towards personalized cardiovascular prevention, according to the researchers behind the study.
"This is an important discovery because it gives us an opportunity to intervene at a stage when the disease is still asymptomatic. At the asymptomatic stage, atherosclerosis can be stopped and even reversed if the right measures are taken. Our results can help to design patient-specific interventions that lead to better health," says Bruna Gigante, associate professor at the Department of Medicine, Solna, Karolinska Institutet. She continues:
"The next step in our research is to conduct studies and understand if drugs antagonizing this pathway driven by IL6R can reverse the aggressive development of atherosclerosis in this selected group of individuals.
The study was funded by the Swedish Heart-Lung Foundation, the Swedish Research Council, and the Foundation for Former Servants. There are no reported conflicts of interest.
Publication: "A multi-omics approach uncovers causality of IL6R on endotypes of subclinical carotid atherosclerosis and the possible role of the IL6R/OSMR pathway," Qiao Sen Chen, Hanna M Björck, Otto Bergman, Damiano Baldassarre, Gunnar Engström, Antonio Gallo, Anders Gummesson, Ulf Hedin, Sudhir Kurl, Lars Lind, Ljubica Matic, Douw Johannes Mulder, Matteo Pirro, Kai Savonen, Stefan Söderberg, Fabrizio Veglia, Elena Tremoli, Carl Johan Östgren, Per Eriksson, Rona J Strawbridge, Bruna Gigante, Cardiovascular Research, online October 22, 2025, doi: 10.1093/cvr/cvaf177
Facts about atherosclerosis:
Atherosclerosis, or hardening of the arteries, is a disease in which plaque builds up in the arteries, which can lead to reduced blood flow. Plaque consists of fat, cholesterol, calcium, and other substances found in the blood. The disease can lead to serious cardiovascular diseases such as heart attack and stroke. Risk factors include high blood pressure, high cholesterol, smoking, diabetes, and an unhealthy lifestyle.
