Abstract Body (Do not enter title and authors here): Introduction/Background: We previously demonstrated that an open-source deep learning model (CXR-CVD Risk) can predict 10-year major adverse cardiovascular events (myocardial infarction & stroke), based on a chest radiograph image (CXR). As deep learning models are black boxes, establishing the biological processes the model captures to predict risk may help build understanding and trust in the model.

Research Questions/Hypothesis: To test associations between deep-learning derived CXR-CVD Risk and markers of cardiovascular disease including coronary artery calcium (CAC) and stenosis ≥50% on CT, systolic blood pressure (SBP), ankle brachial index (ABI), and prevalent myocardial infarction and stroke.

Methods/Approach: We conducted external validation of CXR-CVD-Risk in two cohorts: 1) 2,097 volunteers in the Project Baseline Health Study (PBHS) and 2) 1,644 Mass General Brigham Biobank (MGBB) patients. The CXR-CVD-Risk model estimated 10-year cardiovascular event risk (probability between 0 and 1) from a CXR image. We calculated linear associations with SBP, ABI, and the logarithm of coronary artery calcium and odds ratios for prevalent hypertension, myocardial infarction, stroke, and, in the MGBB, coronary artery stenosis ≥50%. Analyses were adjusted for age, BMI, sex, smoking status, and enrolling site.

Results/Data: CXR-CVD-Risk was associated with CAC in both populations (PBHS: 1.11-fold increase, 95% CI: [1.07-1.16]; MGBB: 1.03-fold increase [1.01-1.05] in CAC per 1% increase in CXR-CV-Risk). CXR-CVD-Risk was also associated with SBP (0.59 mmHg increase [0.24-0.93] in SBP per 1% increase in CXR-CV-Risk), history of hypertension, history of myocardial infarction, and stroke. There was an inverse association with ABI (0.010 decrease [0.005-0.014] in ABI) in the PBHS. In the MGBB, CXR-CVD-Risk was associated with coronary artery stenosis ≥50% (OR = 1.004 [1.002-1.007]). All estimates are after covariate adjustment.

Conclusion: This deep learning CXR risk score was associated with coronary artery disease (calcium score and stenosis ≥50%), CVD risk factors, and prevalent CVD. Opportunistic screening using CXRs in the electronic record can identify patients at high risk of CVD who may benefit from prevention.