Association Between Liver Fibrosis, Plasma Volume Status, and Cardiovascular Mortality: The Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases

AIMS: Increasing evidence shows an interrelationship between liver injury and cardiovascular disease. This study aimed to investigate the interrelationship between subclinical congestion, liver fibrosis, and cardiovascular disease mortality. METHODS AND RESULTS: This retrospective cohort study, using data from the Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases, included 8689 participants (mean age 69.7 years, 49.1% women) who were recruited during health checkups. Liver fibrosis and systemic congestion were assessed by the fibrosis-4 (FIB-4) index and plasma volume status (PVS), respectively. PVS was modestly but significantly associated with the FIB-4 index at baseline. During a median follow-up of 9.3 years, 387 (4.5%) cardiovascular deaths occurred. The incidence rates of cardiovascular mortality were 3.95, 5.15, and 14.5 per 1000 person-years in the low (<1.3), indeterminate (1.3-2.67), and high FIB-4 index (>2.67) groups, respectively. In the multivariable Cox proportional hazard regression analysis, compared with the low FIB-4 index group, the high FIB-4 index group showed significantly increased hazard ratios (HRs) for mortality due to cardiovascular (HR 2.34; 95% confidence interval [CI] 1.78-3.06), cardiac (HR 2.43; 95% CI 1.75-3.39), and cerebrovascular (HR 2.18; 95% CI 1.37-3.48) diseases, even after adjusting for PVS. Moreover, the incidence of heart failure-related mortality, but not ischaemic heart disease-related mortality, was increased in the indeterminate FIB-4 index group. CONCLUSIONS: Systemic congestion may partially contribute to the progression of liver fibrosis, and advanced liver fibrosis increases cardiovascular mortality rates, independent of congestion, and heart failure-related mortality was more prominent than ischaemic heart disease-related mortality.