Blood Protein Patterns May Predict Inherited Heart Disease Risk
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A new study reveals a potential biomarker for hereditary atherosclerosis, offering a path toward earlier detection and intervention for those with a family history of heart attacks.
A specific pattern of proteins circulating in the blood may signal an increased risk of developing atherosclerosis, or hardening of the arteries, even in the absence of traditional risk factors like high blood pressure or cholesterol. Researchers at Karolinska Institutet in Sweden published their findings on Thursday, February 6, 2025, in the journal Circulation: Genomic and Precision Medicine.
The study analyzed blood samples from over 4,000 individuals without known heart disease, meticulously linking the results to their family’s cardiovascular health history. The investigation identified 38 distinct proteins that appeared more frequently in individuals with a family history of cardiovascular disease, many of which are associated with inflammation and fat metabolism.
“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,” explained a lead researcher from the Department of Clinical Research and Education at Södersjukhuset, Karolinska Institutet. This suggests a biological predisposition independent of lifestyle choices.
Uncovering Hereditary Risk Through Comprehensive Data
The research leveraged data from the Swedish population study SCAPIS (Swedish Coronary Angiography and Biomarker Pilot Study), which included detailed health examinations and computed tomography scans of participants’ coronary arteries. By cross-referencing this data with the Swedish Multigenerational Register, researchers were able to demonstrate a clear correlation: individuals with a family history of early-onset coronary heart disease exhibited more extensive coronary atherosclerosis, measured by the number of diseased vessel segments.
Further analysis revealed that certain proteins had a particularly strong association with the severity of atherosclerosis in those with a hereditary risk. These included the LDL receptor – crucial for regulating cholesterol levels – and PECAM1, a protein known to influence blood vessel function.
Identifying Proteins with a Causal Role
The team also employed genetic analyses to explore whether specific proteins might directly contribute to the development of heart attacks. The results pointed to follistatin, PCSK9, and PECAM1 as potential causal factors. These findings offer valuable insights into the underlying mechanisms driving coronary artery disease, whether inherited or developed later in life.
“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,” stated a senior physician and associate professor involved in the study. This discovery could pave the way for targeted preventative measures and personalized treatment strategies.
The Karolinska Institutet-led study, a collaborative effort within the SCAPIS project, underscores the importance of considering family history when assessing cardiovascular risk. While the study’s funding sources are detailed in the full scientific publication, the implications of these findings are clear: a deeper understanding of the proteomic landscape of hereditary heart disease is within reach, offering hope for improved prevention and treatment in the future.
Source: Wahrenberg, A., et al. (2025). Plasma Protein Profile Associated With a Family History of Early-Onset Coronary Heart Disease. Circulation: Genomic and Precision Medicine. doi: 10.1161/circgen.124.005220. https://www.ahajournals.org/doi/10.1161/CIRCGEN.124.005220.
