Lipidomic Risk Score to Enhance Cardiovascular Risk Stratification for Primary Prevention

Authors

Jingqin Wu
Corey Giles
Aleksandar Dakic
Habtamu B. Beyene
Kevin Huynh
Tingting Wang
Thomas Meikle
Gavriel Olshansky
Agus Salim
John Blangero, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

7-30-2024

Abstract

Background

Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score(FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies.

Objectives

This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS.

Methods

The LRS was developed via a machine learning workflow using ridge regression on the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab; n = 10,339). It was externally validated with the Busselton Health Study (n = 4,492), and its predictive utility for coronary arterycalcium scoring (CACS)–based outcomes was independently validated in the BioHEART cohort (n = 994).

Results

LRS significantly improved discrimination metrics for the intermediate-risk group in both AusDiab and Busselton Health Study cohorts (all P < 0.001), increasing the area under the curve for CVD events by 0.114 (95% CI: 0.1123-0.1157) and 0.077 (95% CI: 0.0755-0.0785), with a net reclassification improvement of 0.36 (95% CI: 0.21-0.51) and 0.33 (95% CI: 0.15-0.49), respectively. For CACS-based outcomes in BioHEART, LRS achieved a significant area under the curve improvement of 0.02 over the FRS (0.76 vs 0.74; P< 1.0 × 10-5). A simplified, clinically applicable version of LRS was also created that had comparable performance to the original LRS.

Conclusions

LRS, augmenting the FRS, presents potential to improve intermediate-risk stratification and to predict atherosclerotic markers using a simple blood test, suitable for clinical application. This could facilitate the triage of individuals for noninvasive imaging such as CACS, fostering precision medicine in CVD prevention and management.

Comments

http://creativecommons.org/licenses/by-nc-nd/4.0/

Recommended Citation

Wu, J., Giles, C., Dakic, A., Beyene, H. B., Huynh, K., Wang, T., ... & Meikle, P. J. (2024). Lipidomic risk score to enhance cardiovascular risk stratification for primary prevention. Journal of the American College of Cardiology, 84(5), 434-446. https://doi.org/10.1016/j.jacc.2024.04.060

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

First Page

434

Last Page

446

Publication Title

Journal of the American College of Cardiology

DOI

10.1016/j.jacc.2024.04.060

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics