Angiopoietin-like protein 4 (ANGPTL4) is a hepatokine implicated in fat metabolism regulation. Its genetic inactivation has been associated with improved glucose homeostasis, while elevated plasma ANGPTL4 levels are observed in diabetic and obese individuals. However, the potential link between ANGPTL4 and diabetes- or obesity-related complications remains uncertain. This study aimed to explore whether plasma ANGPTL4 levels could serve as predictors of cancer mortality, cardiovascular mortality, and all-cause mortality in a community-based cohort.

Material and methods:
A community-based cohort study was conducted, where fasting plasma ANGPTL4 concentrations were measured at baseline, and vital status was ascertained through linkage with the National Health Insurance Research Database in Taiwan.

During a 10.46-year follow-up period, 29 (2.49%) of the 1163 participants died. Subjects within the highest tertile of plasma ANGPTL4 levels exhibited the lowest survival rate. In unadjusted models, plasma ANGPTL4 significantly predicted all-cause mortality, cancer mortality, and cardiovascular or cancer-related mortality. Upon adjustment for confounders including age, sex, smoking, BMI, hypertension, DM, and renal function, each standard deviation increase in plasma ANGPTL4 was associated with HRs of 1.35 (95% CI 1.01-1.80, p<0.05) for all-cause mortality, 1.41 (95% CI 0.94-2.10, p=0.094) for cancer mortality, and 1.40 (95% CI 1.02-1.94, p<0.05) for cardiovascular or cancer-related mortality. Additionally, plasma ANGPTL4 contributed more significantly to predicting cardiovascular or cancer-related mortality and all-cause mortality compared to other predictors, such as sex, smoking, BMI, history of hypertension, history of diabetes, and eGFR.

Plasma ANGPTL4 emerges as a promising biomarker capable of predicting 10-year mortality and enhancing risk prediction beyond established risk factors.

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