SA ProtRSs of coronary calcification and carotid plaque progression may provide additional value over traditional risk assessment, highlighting their potential in refining risk stratification and guiding targeted intervention strategies.
Key Findings
Results
Protein risk scores for subclinical atherosclerosis progression were built from 14 proteins each for coronary artery calcium (CAC) and carotid plaque progression, explaining modest proportions of variance.
Developed in a community cohort of 903 individuals with repeated SA assessments (CAC or carotid plaque) over 6 years (2008-2009 to 2013-2014).
Proteins were selected from a panel of 117 proteins using LASSO regression.
The ProtRSs explained 17.1% (CAC) and 18.4% (plaque) of the respective variances.
Results
Protein effect sizes on SA progression were strongly concordant with their effect sizes on incident ASCVD.
The correlation between effect sizes was reported as r > 0.75.
This supports the relevance of SA progression proteins to clinical ASCVD outcomes.
Results
Both SA ProtRSs were associated with incident ASCVD risk.
Each standard deviation increase in the CAC ProtRS was associated with a hazard ratio of 1.36 (95% CI 1.20-1.54).
Each standard deviation increase in the plaque ProtRS was associated with a hazard ratio of 1.38 (95% CI 1.23-1.54).
Evaluated in a case-cohort of 1,835 individuals with median follow-up of 10.4 years (2007-2008 to 2018-2021).
Results
Adding the SA ProtRSs to a guideline-recommended traditional risk score improved risk reclassification.
Net reclassification improvement was 0.127 (p < 0.001).
Incremental value was assessed relative to a guideline-recommended traditional risk score.
Results
A substantial share of traditional intermediate-risk individuals was reclassified into the high-risk category with a high observed event rate.
18.6% of traditional intermediate-risk individuals were reclassified as high-risk.
Their 10-year ASCVD event rate was 10.9%, indicating the need for preventive interventions.
Results
Among traditional high-risk individuals, a subset was identified as having an even higher event rate.
32.8% of traditional high-risk individuals were identified as having a higher rate (13.7%).
The authors suggest this indicates a requirement for intensified management.
Discussion
The authors note that external validation of the ProtRSs at larger scale is still needed.
The main stated limitation is that the predictive value of ProtRSs warrants further large-scale external validation.
What This Means
This study looked at whether blood protein patterns could help identify people whose artery disease is silently getting worse, and whether that information could improve predictions of future heart attacks and strokes. Researchers followed 903 people in a community whose coronary artery calcium or carotid plaque was measured twice over about 6 years. From 117 blood proteins, they picked 14 for each type of artery change to build a protein risk score. These scores explained only about 17-18% of the differences in how much the artery disease progressed.
The scores were then tested in 1,835 people followed for a median of about 10 years. Higher scores were linked to more heart and blood vessel events (about a 36-38% higher hazard per standard deviation increase). Adding the scores to a standard guideline-based risk calculator improved how people were sorted into risk groups. About 19% of people classed as intermediate risk were moved to high risk, and their 10-year event rate was about 11%. About a third of those already considered high risk turned out to have an even higher rate (about 14%).
This research suggests protein-based scores might help refine who may benefit from earlier or more intensive prevention. However, the authors note that the scores need to be validated in larger, independent groups before they can be used more widely.
Huang Y, Gao R, Li J, Yang B, Huang K, Chen S, et al.. (2026). Plasma proteomic signatures of subclinical atherosclerosis progression for cardiovascular risk stratification: A cohort study.. PLoS medicine. https://doi.org/10.1371/journal.pmed.1005265