P1632A possible independent contribution of liver stiffness to the development of heart failure in its early stage

Abstract Background Heart failure (HF) is a heterogeneous condition. The reduced liver blood flow and hepatic congestion associated with HF causes liver damages leading to liver sclerosis. Fibrosis 4 score (FIB-4 score), a marker of liver sclerosis, is easily calculated from age, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) level and blood platelet count (PLT). Liver stiffness is known to be associated with vascular damages, including arterial stiffness and central hemodynamics. These vascular damages also cause the new onset of HF. However, it remains to be clarified whether liver stiffness is a direct risk factor for HF or whether its association with HF is mediated by vascular damage. We conducted cross-sectional and prospective longitudinal studies to examine whether FIB-4 score is directly associated with the serum NT-pro-BNP levels or the association is mediated by arterial stiffness and/or abnormal central hemodynamics. Methods and results In 3,040 health Japanese subjects with serum NT-pro-BNP levels <125 pg/ml, the FIB-4 score was calculated, and the serum NT-pro-BNP levels, brachial-ankle pulse wave (baPWV) velocity, radial augmentation index (rAI), second peak of the radial pressure waveform (SBP2) and PP2 (SBP2 – diastolic blood pressure) were measured. These parameters were measured again after a 3-year interval in 2,135 subjects. Pearson's correlation analysis demonstrated that FIB-4 score was significantly correlated with baPWV, rAI, SBP2, PP2 and the log-transformed the serum NT-pro-BNP levels. Multivariate linear regression analysis demonstrated a significant cross-sectional association of the FIB-4 scores with the log-transformed the serum NT-pro-BNP levels (beta = 0.08, p<0.01), but not with the baPWV, rAI, SBP2 and PP2. The change of serum NT-pro BNP levels during the study period was significantly higher in subjects with increase of the FIB-4 score during the study period (8.2±22.5 pg/ml) than that in those with decrease/no change (5.4±22.3 pg/ml) (p<0.05). The change of FIB-4 score during the study period was significantly associated with the change of the serum NT-pro-BNP levels during the study period (beta = 0.09, p<0.01). Conclusion Liver stiffness may have a significant direct association with the development of HF from the early stage, without the mediation of arterial stiffness and/or abnormal central hemodynamics. Therefore, the FIB-4 score appears to serve as a direct risk factor for HF from the early stage, and its association with HF may not be mediated by vascular damages.