Abstract 4361990: A multi-proteomic Risk Score Predicts Adverse Cardiovascular Outcomes in Patients with Angina and Non-obstructive Coronary Artery Disease

Background: Angina with nonobstructive coronary arteries (ANOCA) has emerged as a significant contributor to major adverse cardiovascular events (MACE) and cardiovascular (CV) death. Risk stratification using biomarkers reflecting activation of distinct pathophysiological pathways remains limited, hindering optimal management. This study aimed to assess combinations of biomarkers and their association with adverse outcomes in ANOCA patients. Methods: We studied patients with ANOCA, defined as <50% stenosis in epicardial coronary arteries, enrolled in the Emory Cardiovascular Biobank. Baseline levels of high-sensitivity C-reactive protein (hsCRP), soluble urokinase plasminogen activator receptor (suPAR), high-sensitivity troponin I (hsTnI), and brain natriuretic peptide (BNP) were measured. MACE included CV death, myocardial infarction, stroke, heart failure hospitalization, or revascularization. A Biomarker Risk Score (BRS) was calculated by assigning 1 point for each biomarker above its median (ranges 0-4). Fine-Gray subdistribution models adjusted for age, sex, hypertension, diabetes, hyperlipidemia, and statin use assessed associations between biomarkers and outcomes. Discrimination was evaluated using Harrell’s C-statistic, with performance improvement assessed by Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Results: Among 620 patients (mean age 58.8±12.0 years; 49% female), median follow-up was 4.2 years. After adjustment, BNP, hsCRP, and hsTnI were associated with MACE; BNP, hsCRP, and suPAR were associated with CV death (Figure 1). BRS distribution was: 0 (10.6%), 1 (25.6%), 2 (29.7%), 3 (21.8%), and 4 (12.3%). Compared to BRS 0–1, those with BRS 3–4 had significant higher risk of MACE (HR 2.50, 95% CI 1.38–4.50; p=0.002) and CV death (HR 4.24, 95% CI 1.72–10.46; p=0.002); BRS 2 showed intermediate risk (Figure 2). Adding all 4 biomarkers to clinical covariates improved prediction of CV death (C-statistic 67.5 to 82.2; p=0.03), with significant IDI (0.075; p<0.001) and NRI (0.378; p=0.007). Improvements for MACE were modest and not statistically significant (C-statistic 61.5 to 67.5; p=0.08; IDI: 0.021; p=0.07; NRI: 0.118; p=0.19). Conclusions: In patients with ANOCA, elevated levels of BNP, hsTnI, hsCRP, and suPAR predicted MACE and CV death and improved risk discrimination. Activation of pathophysiologic pathways associated with ASCVD progression can help risk stratification in patients with ANOCA.