Abstract 14022: N-terminal Prohormone of B-type Natriuretic Peptide Levels Partly Mediate the Relationship of Advanced Hepatic Fibrosis With Mortality in Coronary Artery Disease

Abstract

Background Advanced hepatic fibrosis (AHF) is associated with cardiac remodeling and adverse outcomes in patients with coronary artery disease (CAD). The mechanistic basis of this relationship and the contribution of the natriuretic peptide system is unclear. Hypothesis: The association of AHF with mortality in CAD is mediated by circulating N-terminal prohormone of B-type natriuretic peptide (NTproBNP) level. Methods: Patients undergoing cardiac catheterization for evaluation of CAD were enrolled in the Emory Cardiovascular Biobank and those with acute myocardial infarction, cirrhosis, and hepatocellular carcinoma were excluded. Plasma NTproBNP was measured, and Fibrosis-4 (FIB-4) index was calculated using age, alanine aminotransferase, aspartate aminotransferase, and platelet count. FIB-4 ≥2.67 was used to define AHF. Association of AHF and NTproBNP with all-cause mortality was studied using multivariable-adjusted Cox models and mediation analyses. Results: Study population included 3,432 patients with mean age 65 y and among them 32% were women, 24% were Black, and 15% had AHF. Median NTproBNP level was 2.5-fold higher among those with AHF (572, 95% CI 225-2203 pg/ml) compared with those without (223, 95% CI 93-689 pg/ml). AHF was independently associated with 49% higher all-cause mortality in multivariable-adjusted Cox models [HR(95% CI): 1.49 (1.26-1.77)]. NTproBNP stratified mortality risk associated with AHF ( Figure ). Patients with AHF and high NTproBNP (≥300 pg/ml) were at the highest risk, while risk in AHF and low NTproBNP (<300 pg/ml) group was similar to those without AHF and low NTproBNP. NTproBNP was independently associated with mortality risk and mediated 61% of the effect of AHF on mortality in causal mediation analysis. Conclusion: NTproBNP partly mediates the excess mortality associated with AHF in patients with CAD. Therapeutic strategies targeting the natriuretic peptide system may help improve outcomes in this high-risk group.