Background: Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), whether NAFLD predicts future CVD events, especially CVD mortality, remains uncertain. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACEs) in a large population-based study. Methods: We identified 3011,588 subjects in the Korean National Health Insurance System cohort without a history of CVD who underwent health examinations from 2009 to 2011. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. A Cox proportional hazards regression analysis was performed to assess association between the FLI and the primary endpoint. Results: During the median follow-up period of 6 years, there were 46,010 cases of MACEs (7148 cases of cardiovascular death, 16,574 of non-fatal MI, and 22,288 of ischemic stroke). There was a linear association between higher FLI values and higher incidence of the primary endpoint. In the multivariable models adjusted for factors, such as body weight and cholesterol levels, the hazard ratio for the primary endpoint comparing the highest vs. lowest quartiles of the FLI was 1.99 (95% confidence interval [CIs], 1.91-2.07). The corresponding hazard ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9-2.06), 2.16 (2.01-2.31), and 2.01 (1.90-2.13), respectively (p < 0.001). The results were similar when we performed stratified analyses by age, sex, use of dyslipidemia medication, obesity, diabetes, and hypertension.

Background: Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), whether NAFLD predicts future CVD events, especially CVD mortality, remains uncertain. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACEs) in a large population-based study. Methods: We identified 3,011,588 subjects in the Korean National Health Insurance System cohort without a history of CVD who underwent health examinations from 2009 to 2011. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. A Cox proportional hazards regression analysis was performed to assess association between the FLI and the primary endpoint. Results: During the median follow-up period of 6 years, there were 46,010 cases of MACEs (7,148 cases of cardiovascular death, 16,574 of non-fatal MI, and 22,288 of ischemic stroke). There was a linear association between higher FLI values and higher incidence of the primary endpoint. In the multivariable models adjusted for factors, such as body weight and cholesterol levels, the hazard ratio for the primary endpoint comparing the highest vs. lowest quartiles of the FLI was 1.99 (95% confidence interval [CIs], 1.91–2.07). The corresponding hazard ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9-2.06), 2.16 (2.01-2.31), and 2.01 (1.90-2.13), respectively (p<0.001). The results were similar when we performed stratified analyses by age, sex, use of dyslipidemia medication, obesity, diabetes, and hypertension. Conclusions: Our findings indicate that the FLI, which is a surrogate marker of NAFLD, has prognostic value for detecting individuals at higher risk for cardiovascular events.

KEYWORDS 2 cardiovascular disease, mortality, non-alcoholic fatty liver disease, fatty liver index 3 Abstract Background Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), it remains uncertain whether NAFLD predicts future CVD events, especially CVD mortality. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACE) in a large population-based study.Methods We identified 3,011,588 subjects without a history of CVD who underwent health examinations from 2009 to 2011 in the Korean National Health Insurance System cohort. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. Cox proportional hazards regression analysis was performed to assess the independent association between FLI and the primary endpoint.Results During the median follow-up of 6 years, there were 46,010 cases of MACE (7,148 cases of cardiovascular death, 16,574 non-fatal MI, and 22,228 ischemic stroke). There was a linear association between higher FLI values and higher incidence of the primary endpoint. In the multivariable models adjusted for factors including body weight and cholesterol levels, the hazard ratio (95% CIs) for the primary endpoint comparing the highest vs. lowest quartiles of FLI was 1.99(1.91-2.07). The corresponding odds ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9-2.06), 2.16 (2.01-2.31), and 2.01 (1.90-2.13), respectively. The results were similar when we stratified analysis by age, sex, dyslipidemia medication, obesity, diabetes, and hypertension.Conclusions Our findings indicate that FLI, a surrogate marker of NAFLD, has prognostic value for