Protein Risk Scores for Subclinical Atherosclerosis Improve Cardiovascular Risk Stratification
On October 20, 2026, researchers published a study in journals.plos.org demonstrating that new plasma protein risk scores can track subclinical atherosclerosis progression and refine cardiovascular risk stratification beyond traditional clinical scoring methods.
Detecting Early Vascular Changes Through Plasma Proteins
Atherosclerotic cardiovascular disease remains a leading contributor to global mortality and health loss. Traditional risk stratification tools often fail to identify individuals who harbor a substantial subclinical atherosclerotic burden but fall into intermediate- or low-risk categories. To address this limitation, investigators sought to determine whether plasma proteins capture early vascular changes before clinical events occur.
Imaging-based coronary artery calcium scoring serves as an established method for enhancing risk assessment. However, widespread clinical scanning faces hurdles due to limited computed tomography access, radiation exposure, and cost constraints. The newly published research investigates whether blood-based biomarkers can offer a sensitive and accessible alternative.
Constructing the Protein Risk Scores in Community Cohorts
The study utilized a discovery cohort of 903 participants from the Beijing Community-Based Cohort of Atherosclerosis Study who underwent repeated subclinical atherosclerosis examinations—including coronary artery calcium and carotid plaque assessments—over a six-year period between 2008–2009 and 2013–2014. From a panel of 117 proteins, researchers selected specific biomarkers using least absolute shrinkage and selection operator regression to build protein risk scores for coronary artery calcium and plaque progression.
Each resulting protein risk score incorporated 14 distinct proteins. These panels explained 17.1% and 18.4% of the respective variances in coronary calcification and plaque progression. The effect sizes of these proteins showed strong concordance with incident atherosclerotic cardiovascular disease, displaying correlation coefficients exceeding 0.75.
Validating Predictive Performance in Prospective Case-Cohorts
To evaluate how well these biomarkers predict future events, researchers analyzed a prospective case-cohort of 1,835 participants drawn from the International Collaborative Study of Cardiovascular Disease in Asia and the China Multi-Center Collaborative Study of Cardiovascular Epidemiology cohorts, with a median follow-up of 10.4 years from baseline assessments conducted between 2007–2008 and 2018–2021.
Each standard deviation increase in the coronary artery calcium and plaque protein risk scores associated with hazard ratios of 1.36 and 1.38 for incident atherosclerotic cardiovascular disease, respectively. Adding these protein risk scores to traditional risk models yielded a net reclassification improvement of 0.127. The approach reclassified 18.6% of individuals previously deemed at intermediate risk into the high-risk category, showing that early preventive care is needed. Meanwhile, 32.8% of traditional high-risk individuals were identified as having an even higher event rate, signaling a requirement for intensified clinical management.