Research from the Karolinska Institutet has identified a specific pattern of proteins in the blood that may indicate an increased risk of hereditary atherosclerosis. The study, published on November 7, 2025, in the journal Circulation: Genomic and Precision Medicine, focused on close relatives of individuals who experienced heart attacks at a young age.
The investigation analyzed blood samples from over 4,000 participants without known heart disease and assessed their family history of cardiovascular conditions. Researchers discovered 38 distinct proteins in the blood, many of which are associated with inflammation and fat metabolism, that were significantly more prevalent in individuals with a family history of cardiovascular disease.
Key Findings on Protein Levels and Heart Disease
According to Agnes Wahrenberg, the first author of the study and researcher at the Department of Clinical Research and Education at Södersjukhuset, “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.”
The research utilized data from the Swedish population study SCAPIS, where participants underwent comprehensive health examinations, including computed tomography of the coronary arteries. By linking various registers, including the Swedish Multigenerational Register, the study showed that individuals with a family history of early-onset coronary heart disease exhibited more widespread coronary atherosclerosis, measured by the number of affected vessel segments.
Further, specific proteins demonstrated a stronger correlation with the severity of atherosclerosis in those with hereditary risk. Among these were the LDL receptor and PECAM1, a protein that plays a role in blood vessel function.
Potential Mechanisms Behind Coronary Artery Disease
The findings of this study suggest a distinct biological profile associated with hereditary atherosclerotic disease. Per Svensson, the last author and associate professor at the same department, noted, “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.”
Researchers also conducted genetic analyses to explore whether certain proteins may have a direct causal role in the development of heart attacks. The results indicated that proteins such as follistatin, PCSK9, and PECAM1 could play a significant role in this process.
The overall findings contribute to a better understanding of the mechanisms underlying coronary artery disease, whether hereditary or due to other factors. The study, which was conducted as part of the SCAPIS project, was funded as detailed in the scientific publication. The researchers reported no conflicts of interest.
