Researchers at Swedish institutions, including Karolinska Institutet, have identified gene variants that increase the risk of atherosclerosis. The goal is for these new findings to enable earlier detection of atherosclerosis and improved treatment of cardiovascular diseases such as heart attack and stroke. The study has been published in the journal Nature Communications.
Atherosclerosis is the disease process that leads to the formation of plaques in the blood vessels that supply the body's organs with blood. These plaques grow over time and can cause a sudden stop in the blood supply.
If this happens in the heart's coronary arteries, acute oxygen deficiency occurs in the heart muscle, causing a heart attack. If it occurs in plaques in the carotid arteries, the clot can travel with the blood to the brain and cause a stroke.
The current study, a collaboration between universities and university hospitals across Sweden, represents the largest genetic mapping of atherosclerosis, using advanced imaging diagnostics.
"Atherosclerosis is a silent killer. It becomes suddenly manifested when a myocardial infarction or a stroke occurs, but signs of atherosclerosis can be visualized and quantified in both carotid and coronary arteries. The genetic variants we have identified predispose to atherosclerosis and therefore may allow us to identify individuals amenable for early and aggressive prevention strategies", says Bruna Gigante , last author of the study, senior physician and associate professor at the Department of Medicine in Solna, Karolinska Institutet.
Twenty Genetic Variants Identified
The study is based on data from the population study SCAPIS, the largest in Sweden within heart, vascular, and lung research, involving 30,000 randomly selected Swedes aged 50-64 who have undergone extensive health examinations. What distinguishes SCAPIS are the highly detailed measurements of atherosclerosis made using advanced imaging diagnostics, including both computed tomography and ultrasound.
This enabled the researchers to examine several million genetic variants spread across the entire genome regarding their impact on the risk of atherosclerosis in the coronary arteries, which can cause heart attacks. Twenty genetic variants were found to have a statistically significant association.
The study also included similar analyses of atherosclerosis of the carotid arteries, which can lead to stroke. When the coronary and carotid results were compared, several differences emerged, suggesting different underlying disease mechanisms.
Atherosclerosis is common, and even relatively advanced atherosclerosis can be completely asymptomatic. For many of those affected by heart attack or stroke, it comes without warning. Cardiovascular disease is the most common cause of death in Sweden and most other countries.
"The study is an important piece of the puzzle in understanding why atherosclerosis develops, which could ultimately lead to new ways of preventing the disease process. We also hope to develop genetic tests to identify people at high risk of being affected", says Anders Gummesson, leader of the study, associate professor of molecular medicine at the University of Gothenburg, and senior physician in clinical genetics at Sahlgrenska University Hospital.
Result will be open to other researchers
The results will be available to other researchers worldwide so they can use them in their research.
"Above and beyond our current results, it is important to underline that the clinical, molecular, and imaging data collected in SCAPIS represent a golden mine for current and future epidemiological research in Sweden. Furthermore, through SCAPIS, close collaborations among universities have been consolidated, expertise maximized in different projects and a modern infrastructure for senior and young investigators has been created", says Bruna Gigante.
SCAPIS (Swedish CArdioPulmonary BioImage Study) is led and operated by six Swedish universities and six university hospitals: Sahlgrenska Academy, University of Gothenburg, Uppsala University, Karolinska Institutet, Umeå University, Lund University, Sahlgrenska University Hospital, Region Västra Götaland, Karolinska University Hospital, Skåne University Hospital, University of New South Wales, and Danderyd University Hospital.
The research is conducted in close collaboration with the Heart-Lung Foundation, which is the main financier. The project is coordinated at the University of Gothenburg.
Publication
"A genome-wide association study of imaging-defined atherosclerosis" , Anders Gummesson, Per Lundmark, Qiao Sen Chen, Elias Björnson, Koen F. Dekkers, Ulf Hammar, Martin Adiels, Yunzhang Wang, Therese Andersson, Göran Bergström, Carl-Johan Carlhäll, David Erlinge, Tomas Jernberg, Fredrik Landfors, Lars Lind, Maria Mannila, Olle Melander, Carlo Pirazzi, Johan Sundström, Carl Johan Östgren, Cecilia Gunnarsson, Marju Orho-Melander, Stefan Söderberg, Tove Fall & Bruna Gigante, Nature Communications, online March 31, 2025, doi: 10.1038/s41467-025-57457-7
