A specific pattern of proteins in the blood may reflect an increased risk of hereditary atherosclerosis. This is shown in a new study from Karolinska Institutet, examining close relatives of people who had suffered a heart attack at a young age. The study has been published in the journal Circulation: Genomic and Precision Medicine.
The researchers analyzed blood samples from over 4,000 people without known heart disease and linked the results to the history of cardiovascular disease in parents or siblings of participants. The study identified 38 different proteins found in blood, many linked to inflammation and fat metabolism, that were more prevalent in people with a family history of cardiovascular disease.
'We see that certain proteins, such as follistatin and cathepsin D, are significantly elevated in people with a family history of early-onset coronary heart disease, regardless of traditional risk factors such as blood pressure and cholesterol,' says Agnes Wahrenberg, first author of the study and researcher at the Department of Clinical Research and Education, Södersjukhuset, Karolinska Institutet.
The study is based on data from the Swedish population study SCAPIS, in which participants took part in comprehensive health examinations, including computed tomography of the coronary arteries. By linking registers, including the Swedish Multigenerational Register, the researchers were able to show that people with a family history of early-onset coronary heart disease had more widespread coronary atherosclerosis, measured as the number of diseased vessel segments.
In addition, certain proteins were found to have a stronger association with the degree of atherosclerosis in people with hereditary risk. These included the LDL receptor and PECAM1, a protein that affects blood vessel function.
'Our results suggest that there is a specific biological pattern connected to hereditary atherosclerotic disease, which may help to explain why some people are affected despite leading a healthy lifestyle,' says Per Svensson, last author of the study, associate professor at the same department, and senior physician at Södersjukhuset.
The researchers also used genetic analyses to investigate whether certain proteins may have a direct causal role in the development of heart attacks. The results indicate that follistatin, PCSK9 and PECAM1, are such proteins. The overall results of the study suggest possible mechanisms underlying the development of coronary artery disease, whether hereditary or not.
Karolinska Institutet led the study, which is a collaboration within the framework of the SCAPIS project. The funding of this study is stated in the scientific publication. The researchers report no conflicts of interest.
Publication:
Plasma Protein Profile Associated With a Family History of Early-Onset Coronary Heart Disease , Agnes Wahrenberg, Lars Lind, Natan Åberg, Henrike Häbel, Marika Ström, Anders Mälarstig, Patrik K.E. Magnusson, Ralf-Kuja Halkola, Göran Bergström, Gunnar Engström, Emil Hagström, Tomas Jernberg, Stefan Söderberg, Carl Johan Östgren, Per Svensson, online 7 November 2025, doi: 10.1161/CIRCGEN.124.005220.
