Abstract 4364284: A Machine Learning-Derived Socio-Environmental Risk Score More Accurately Predicts Cardiovascular Events and Better Addresses Health Inequities than Social Deprivation Index

Z Zhuo Chen S Sai Rahul Ponnana (Case Western Reserve University, Cleveland, Ohio, United States) J Jean-Eudes Dazard (Case Western Reserve University, Cleveland, Ohio, United States) T Tong Zhang W Weichuan Dong (Houston Methodist, Houston, Texas, United States) R Robert Okyere (University Hospitals, Cleveland, Ohio, United States) S Santosh Sirasapalli (Case Western Reserve University, Cleveland, Ohio, United States) S Salil Deo (Case Western Reserve University, Cleveland, Ohio, United States) H Haitham Khraishah K Khurram Nasir S Sadeer Al-Kindi S Sanjay Rajagopalan

Abstract

Introduction: The American Heart Association’s PREVENT equation now includes zip-code level Social Deprivation Index (SDI), highlighting the growing role of socio-environmental (SE) factors in risk prediction. However, concerns remain about fully capturing the breadth of exposures, particularly those prevalent in disadvantaged populations, within existing tools. This study sought to develop and evaluate a novel SE Risk Score using machine learning, and to compare its utility against SDI in the context of Coronary Artery Calcium (CAC) screening. Research Questions: Whether a novel machine learning-derived SE Risk Score incorporating more than 150 area level environmental pollution, social and economic variables, when added to CAC scores, improves Major Adverse Cardiovascular Events (MACE) prediction than SDI, in Blacks. Methods: We analyzed CAC scores, MACE outcomes, demographics, and census-tract SE variables from the CLARIFY registry (NCT04075162), a large prospective study of no-charge CAC testing (84,233 White and 7,940 Black participants). A SE Score was derived using an XGBoost machine learning model. This SE Score was then compared to zip-code level SDI. Analyses included Cox proportional hazards models, mediation analysis, and model performance evaluation (Harrell’s C-index, area under the curve (AUC), calibration metrics, Net Reclassification Improvement [NRI]) for models including CAC alone, CAC+SE Risk Score, and CAC+SDI. Results: Compared to Whites, Black participants had higher MACE (14.0% vs 6.4%), despite lower mean CAC (151.5 vs 175.5). Adding SE Score to CAC improved C-index from 0.681 to 0.712, while adding census-tract SDI yielded 0.705 and zip-code SDI 0.700 respectively. For Blacks, the AUC at Year 4 improved from 0.642 (CAC alone) to 0.669 (CAC+SE Risk Score), surpassing the 0.672 achieved with CAC+census-tract SDI ( Figures 1 and 2 ). The improvement in risk reclassification was more pronounced for Black individuals (Net Reclassification Improvement: 0.153) than for White individuals (0.081). SE factors mediated 47.12% of the relationship between race and MACE. Conclusion: The machine learning–derived SE Score outperformed SDI in predicting MACE, improving both discrimination and calibration. SE factors mediated the race–MACE link, and their inclusion with CAC scores significantly enhanced risk reclassification, particularly in Black individuals. More refined tools are needed to better assess and address risk in socially disadvantaged populations.

Article Details

Journal Circulation
Volume / Issue Vol. 152, Issue Suppl_3
Published November 04, 2025
ISSN 0009-7322
Publisher Lippincott Williams & Wilkins

Journal Info

Circulation

Lippincott Williams & Wilkins

ISSN: 0009-7322 Health Sciences

Authors (12)

Z

Zhuo Chen

S

Sai Rahul Ponnana

Case Western Reserve University, Cleveland, Ohio, United States

J

Jean-Eudes Dazard

Case Western Reserve University, Cleveland, Ohio, United States

T

Tong Zhang

W

Weichuan Dong

Houston Methodist, Houston, Texas, United States

R

Robert Okyere

University Hospitals, Cleveland, Ohio, United States

S

Santosh Sirasapalli

Case Western Reserve University, Cleveland, Ohio, United States

S

Salil Deo

Case Western Reserve University, Cleveland, Ohio, United States

H

Haitham Khraishah

K

Khurram Nasir

S

Sadeer Al-Kindi

S

Sanjay Rajagopalan