A study of over 2,000 elderly adults found 43 proteins associated with early cardiovascular disease markers, with NT-proBNP, arterial stiffness, and carotid plaque showing the most protein connections — including several never reported before.
43 of 92 proteins linked to early heart disease signsNearly half of the cardiovascular proteins measured were significantly associated with subclinical disease markers in over 2,000 elderly adults.
What the researchers found
Of 92 cardiovascular-related proteins measured, 43 were significantly associated with at least one of 13 subclinical cardiovascular traits. NT-proBNP (a peptide biomarker of heart stress), brachial-ankle pulse-wave velocity (arterial stiffness), and carotid plaque burden had the most protein associations.
Only three proteins — growth/differentiation factor 15, LDL receptor, and interleukin-1 receptor type 2 — were associated with all three of these key traits. Several novel associations were discovered: von Willebrand factor and galectin 4 with carotid plaque, carboxypeptidase A1 and B1 with carotid intima-media thickness, cathepsin D with arterial stiffness, and cathepsin Z, LDL receptor, neurogenic locus homolog protein 3, and TREM-like transcript 2 with NT-proBNP. Sex-specific effects were also observed for some proteins.
Why it matters
Detecting cardiovascular disease before symptoms appear is critical for prevention. This study maps out which proteins in the blood are linked to early, hidden disease processes — long before a heart attack or stroke occurs. The newly discovered protein associations could lead to better blood tests for early risk prediction and identify new biological targets for preventive therapies.
How the study worked
Researchers measured 92 cardiovascular-disease-related proteins using the Olink Cardiovascular III panel in 2,024 elderly participants from the population-based LIFE-Adult study in Germany. They analyzed associations between these proteins and 13 subclinical cardiovascular traits including carotid intima-media thickness, plaque burden, pulse-wave velocities, ankle-brachial index, and NT-proBNP levels, while controlling for 27 covariables including blood counts, risk factors, and lifestyle parameters.
What this study cannot tell us
This is a cross-sectional, observational study, so it cannot establish whether the identified proteins cause cardiovascular changes or are simply markers of them. The study population was elderly and from a single geographic region (Germany), which may limit generalizability. The protein panel was limited to 92 pre-selected cardiovascular proteins, potentially missing important associations with proteins not included in the panel.
How to read the evidence
This is a large population-based observational study with over 2,000 participants and rigorous statistical methodology. Population-based designs provide strong epidemiological evidence, though cross-sectional analysis limits causal inference compared to longitudinal or interventional studies.
When this study was published
Published in 2024, this study uses current proteomics technology and represents the latest wave of cardiovascular biomarker discovery research. Its findings are highly relevant to ongoing efforts in precision cardiovascular medicine.
The bigger picture
This study contributes to the growing field of proteomics-based cardiovascular risk prediction. As blood protein measurement technology becomes more accessible, findings like these could eventually be incorporated into routine screening panels that detect heart disease risk years before clinical symptoms appear. The identification of peptide-processing enzymes (carboxypeptidases) and the peptide biomarker NT-proBNP as central hubs in early disease further highlights the role of peptide biology in cardiovascular health.
Questions still open
- Can the newly identified protein associations be validated in diverse populations and used to build improved cardiovascular risk prediction models?
- Do the novel protein-disease links (e.g., carboxypeptidases with carotid thickness) reflect causal pathways that could be targeted therapeutically?
- How do these protein associations change over time — could longitudinal tracking improve early detection?
Common questions
What is NT-proBNP and why is it important in this study?
What does 'subclinical' cardiovascular disease mean?
Read the original research
Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study.
Atherosclerosis, 398, 118613
Citation
Garcia, Tarcyane; Petrera, Agnese; Hauck, Stefanie M; Baber, Ronny; Wirkner, Kerstin; Kirsten, Holger; Pott, Janne; Tönjes, Anke; Henger, Sylvia; Loeffler, Markus; Peters, Annette; Scholz, Markus. (2024). Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study.. Atherosclerosis, 398, 118613. https://doi.org/10.1016/j.atherosclerosis.2024.118613