Abstract

Background: Non-alcoholic fatty liver disease is increasing in decades and has been recently reported to be associated with cardiovascular disease (CVD). However, the underlying pathophysiology has not been elucidated. Thrombospondin(TSP)-2 is a cardio-protective extracellular matrix, while some clinical studies showed that high serum TSP-2 is a good predictor for adverse events in patients with heart failure. We previously found that in healthy people, serum TSP-2 was associated with insulin resistance, N-terminal pro-brain natriuretic peptide and atrial fibrillation, which suggested a potential CVD risk factor. Therefore, serum thrombospondin-2 can affect on the association between liver fibrosis and CVD. Hypotheses: Serum TSP-2 levels were associated with liver fibrosis in a general population. Methods: We performed a cross-sectional study with a health-check up in 224 participants (mean age: 69.0±7.8 years, men: 42.0%) in Uku, Japan in 2019. Serum TSP was measured by ELISA. Liver fibrosis was defined by the Fibrosis-4 (FIB-4) index ≥2.67, where FIB-4 was calculated as {(ageхaspartate aminotransferase)/(plateletх(alanine aminotransferase) 0.5 )}/10. Continuous serum TSP-2 was modeled using restricted cubic splines with 3 knots (5 th , 50 th , 95th) to allow a nonlinear association with the log odds ratio of liver fibrosis. Results: Mean FIB-4 was 1.92±0.89 and 14.3% of total had liver fibrosis. Age and sex adjusted log odds ratios (ORs) for liver fibrosis was associated with serum TSP-2 non-linearly and the risk accelerate when serum TSP-2 ≥29.5ng/mL(Figure 1). ORs(95% CI) for 29.5 and 31.0 of serum TSP-2 compared to 23.0(median) were 1.57(1.11-2.21) and 1.86(1.25-2.78), respectively. Conclusion: Serum TSP-2, which is a CVD biomarker, was strongly associated with liver fibrosis in the pathological range in a general population. This finding provides a new insight into the pathology in the link between liver fibrosis and CVD.

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