Surrogate scores of advanced fibrosis in NAFLD/NASH do not predict mortality in patients with medium-to-high cardiovascular risk

Untreated non-alcoholic fatty liver disease (NAFLD) may have significant consequences including an increase in mortality and cardiovascular injury. Thus, early detection of NAFLD is currently believed not only to prevent liver-related but also cardiovascular mortality. However, almost nothing is known about coexisting NAFLD in patients with coronary artery disease (CAD). We investigated the impact of surrogate scores of fibrosis in NAFLD in a large cohort of patients referred to coronary angiography. Modeling the common NALFD and fibrosis scores, fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), as splines revealed significant associations with all-cause and cardiovascular mortality when Cox regression models were only adjusted for cardiovascular risk factors that were not already included in the calculation of the scores. Stratifying the scores into quartiles yielded hazard ratios [95% confidence interval (CI)] for all-cause and cardiovascular mortality for the 4th quartile versus the 1st quartile of 2.28 (1.90-2.75) and 2.11 (1.67-2.67) for FIB-4 and of 3.21 (2.61-3.94) and 3.12 (2.41-4.04) for NFS. However, we did not observe an independent association of FIB-4 or NFS with overall or cardiovascular mortality in our prospective CAD cohort after full adjustment for all cardiovascular risk factors [all-cause mortality: HR 1.13 (0.904-1.41) and 1.17 (0.903-1.52); cardiovascular mortality: HR 1.06 (0.8-1.41) and 1.02 (0.738-1.41)]. Thus, neither FIB-4 nor NFS, as surrogate markers for NAFLD/NASH, were independent risk factors for overall or cardiovascular mortality in patients with CAD. Our data show that surrogate risk scores for NAFLD-related fibrosis do not add information in assessing the CVD events in patients with CAD proven by angiography.NEW & NOTEWORTHY We investigated the impact of NAFLD surrogate markers in a large cohort of patients that had been referred to coronary angiography. In contrast to a repeatedly demonstrated increased link of cardiovascular events in patients with NALFD, we demonstrated that NAFLD surrogate markers were not independent risk factors for overall or cardiovascular mortality in patients with CAD. Thus, these markers may not be useful for primary prevention of cardiovascular events in patients with CAD.