Plasma proteomic signatures of subclinical atherosclerosis progression for cardiovascular risk stratification: A cohort study
8 affiliations
- 1Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 2Division of Epidemiology, Guangdong Provincial People's Hospital and Cardiovascular Institute, Guangzhou, China.
- 3Department of Epidemiology and Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
- 4Department of Cardiology, Fujian Provincial Hospital, Fuzhou, China.
- 5Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
- 6Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.
- 7Department of Radiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 8School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Abstract
Background: Existing risk stratification tools inadequately identify individuals with subclinical atherosclerosis (SA) who could benefit from early intervention. This study aimed to develop protein risk scores (ProtRSs) for SA progression and assess their incremental value for atherosclerotic cardiovascular disease (ASCVD) risk prediction. Methods and findings: In a community cohort consisting of 903 individuals undergoing repeated SA assessments (coronary artery calcium [CAC] or carotid plaque) over 6 years (2008–2009 to 2013–2014), protein biomarkers were selected from a panel of 117 proteins using least absolute shrinkage and selection operator (LASSO) regression to construct SA ProtRSs for CAC and plaque progression, respectively, and their predictive abilities for incident ASCVD risk were evaluated based on a guideline-recommended traditional risk score in a case-cohort of 1,835 individuals (2007–2008 to 2018–2021, median follow-up of 10.4 years). The ProtRSs each included 14 proteins for CAC and plaque progression, explaining 17.1% and 18.4% of respective variances. Effect sizes of these proteins on SA progression showed strong concordance with those on incident ASCVD (r > 0.75). Each standard deviation increase in CAC and plaque ProtRSs was associated with hazard ratios of 1.36 (95% confidence interval [CI] [1.20,1.54]) and 1.38 (95% CI [1.23,1.54]) for ASCVD risk, respectively. Addition of the SA ProtRSs to the traditional risk score yielded a net reclassification improvement of 0.127 (p < 0.001). Importantly, 18.6% of traditional intermediate-risk individuals were reclassified into the high-risk category (10-year ASCVD event rate: 10.9%), indicating the need for preventive interventions, whereas 32.8% of traditional high-risk individuals were identified as having an even higher rate (13.7%), suggesting the requirement for intensified management. The main limitation is that the predictive value of ProtRSs warrants further large-scale external validation. Conclusions: 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. Why was this study done?: What did the researchers do and find?: What do these findings mean?: Yani Juang, Ruixin Gao and colleagues developed plasma protein-based risk scores linked to the progression of subclinical atherosclerosis. They found that combining these protein-based risk scores with traditional risk factors could improve prediction of cardiovascular disease risk, but further validation is needed.
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BibTeX
@article{huang2026plasma,
title = {{Plasma proteomic signatures of subclinical atherosclerosis progression for cardiovascular risk stratification: A cohort study}},
author = {Yani Huang and Ruixin Gao and Jianxin Li and Bin Yang and Keyong Huang and Shufeng Chen and Jie Cao and Xiaoqing Liu and Chong Shen and Ling Yu and Liancheng Zhao and Ying Li and Dongsheng Hu and Jianfeng Huang and Bin Lu and Dongfeng Gu and Fangchao Liu and Xiangfeng Lu},
journal = {PLOS Medicine},
year = {2026},
month = oct,
doi = {10.1371/journal.pmed.1005265},
url = {https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005265},
note = {CC BY},
}
RIS
TY - JOUR
TI - Plasma proteomic signatures of subclinical atherosclerosis progression for cardiovascular risk stratification: A cohort study
AU - Yani Huang
AU - Ruixin Gao
AU - Jianxin Li
AU - Bin Yang
AU - Keyong Huang
AU - Shufeng Chen
AU - Jie Cao
AU - Xiaoqing Liu
AU - Chong Shen
AU - Ling Yu
AU - Liancheng Zhao
AU - Ying Li
AU - Dongsheng Hu
AU - Jianfeng Huang
AU - Bin Lu
AU - Dongfeng Gu
AU - Fangchao Liu
AU - Xiangfeng Lu
PY - 2026
DA - 2026/10/20
JO - PLOS Medicine
DO - 10.1371/journal.pmed.1005265
UR - https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005265
AB - Background: Existing risk stratification tools inadequately identify individuals with subclinical atherosclerosis (SA) who could benefit from early intervention. This study aimed to develop protein risk scores (ProtRSs) for SA progression and assess their incremental value for atherosclerotic cardiovascular disease (ASCVD) risk prediction. Methods and findings: In a community cohort consisting of 903 individuals undergoing repeated SA assessments (coronary artery calcium [CAC] or carotid plaque) over 6 years (2008–2009 to 2013–2014), protein biomarkers were selected from a panel of 117 proteins using least absolute shrinkage and selection operator (LASSO) regression to construct SA ProtRSs for CAC and plaque progression, respectively, and their predictive abilities for incident ASCVD risk were evaluated based on a guideline-recommended traditional risk score in a case-cohort of 1,835 individuals (2007–2008 to 2018–2021, median follow-up of 10.4 years). The ProtRSs each included 14 proteins for CAC and plaque progression, explaining 17.1% and 18.4% of respective variances. Effect sizes of these proteins on SA progression showed strong concordance with those on incident ASCVD (r > 0.75). Each standard deviation increase in CAC and plaque ProtRSs was associated with hazard ratios of 1.36 (95% confidence interval [CI] [1.20,1.54]) and 1.38 (95% CI [1.23,1.54]) for ASCVD risk, respectively. Addition of the SA ProtRSs to the traditional risk score yielded a net reclassification improvement of 0.127 (p < 0.001). Importantly, 18.6% of traditional intermediate-risk individuals were reclassified into the high-risk category (10-year ASCVD event rate: 10.9%), indicating the need for preventive interventions, whereas 32.8% of traditional high-risk individuals were identified as having an even higher rate (13.7%), suggesting the requirement for intensified management. The main limitation is that the predictive value of ProtRSs warrants further large-scale external validation. Conclusions: 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. Why was this study done?: What did the researchers do and find?: What do these findings mean?: Yani Juang, Ruixin Gao and colleagues developed plasma protein-based risk scores linked to the progression of subclinical atherosclerosis. They found that combining these protein-based risk scores with traditional risk factors could improve prediction of cardiovascular disease risk, but further validation is needed.
SN - 1549-1676
SN - 1549-1277
ER -