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

Abstract

Background: Untreated 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 co-existing NAFLD in patients with coronary artery disease (CAD). Aims: We investigated the impact of surrogates scores of fibrosis in NAFLD in a large cohort of patients referred to coronary angiography. Results: Modelling the common NALFD and fibrosis scores FIB-4 and 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% CI) for all-cause and cardiovascular mortality for the 4th quartile vs 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. Conclusion: Our data shows that surrogate risk scores for NAFLD-related fibrosis do not add information in assessing the CVD events in patients with CAD proven by angiography.

Association of NAFLD with cardiovascular disease and all-cause mortality: a large-scale prospective cohort study based on UK Biobank

“…Other study also reported that surrogate risk scores for NAFLD-related fibrosis, such as FIB-4 do not add information in assessing the CVD events in patients with CAD proven by angiography. 27 …”

Liver fibrosis scores and prognosis in patients with cardiovascular diseases: A systematic review and meta‐analysis

“…Advanced liver fibrosis is the major and most common pathophysiology of many chronic liver diseases, which frequently coexist and contribute independently to each condition. Previous studies found that NAFLD increased the risk of CAD, HF and AF independently of shared metabolic risk factors 22,23,24,25,32,34 . Furthermore, the risk of incident cardiovascular events correlates with the severity of NAFLD histology, suggesting a possible dose–response relationship 35 .…”

“…This meta-analysis included twelve cohort studies (eleven perspectives and one retrospective) involving 25,252 patients with established cardiovascular disease (nonvalvular atrial fibrillation (AF), 20 myocardial infarction (MI), 21 coronary artery disease (CAD) [22][23][24][25] and heart failure (HF) [26][27][28][29][30][31] ). Six investigations were carried out in Japan, 20,26,27,28,29,30 four in China [21][22][23][24] and one each in Germany 25 and the United States. 31 The sample sizes in these studies ranged from 116 to 5143.…”

“…Previous studies found that NAFLD increased the risk of CAD, HF and AF independently of shared metabolic risk factors. 22,23,24,25,32,34 Furthermore, the risk of incident cardiovascular events correlates with the severity of NAFLD histology, suggesting a possible dose-response relationship. 35 The findings of the present study were in line with the previous data.…”

“…The average age of participants ranged from 56 to 79 years, with a male participation rate ranging from 43% to 79%. FIB-4 was studied as a categorical variable in ten studies 20,21,22,23,24,25,28,29,30,31 and a continuous variable in four. 21,22,24,30 However, NFS was studied as a categorical variable in seven 21,22,23,24,25,27,31 and a continuous variable in five studies.…”