TRAIL or TRAIL-R2 as a predictive biomarker for mortality or cardiovascular events: A systematic review and meta-analysis

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TRAIL-receptor-2 (TRAIL-R2) are associated with atherosclerosis. This meta-analysis aimed to investigate the potential association between TRAIL/TRAIL-R2 with mortality or cardiovascular (CV) events. PubMed, Embase, and the Cochrane Library were searched for reports published up to May 2021. Reports were included when the association between TRAIL or TRAIL-R2 and mortality or cardiovascular events was reported. Considering the heterogeneity between studies, we used the random-effects model for all analyses. Ultimately, the meta-analysis included 18 studies (16,295 patients). The average follow-up ranged from 0.25 to 10 years. Decreased TRAIL levels were negatively associated with all-cause mortality (rank variable, HR, 95% CI: 2.93, 1.94-4.42; I²=0.0%, P_{heterogeneity}=0.835). Increased TRAIL-R2 levels were positively associated with all-cause mortality (continuous variable, HR, 95% CI: 1.43, 1.23-1.65; I²=0.0%, P_{heterogeneity}=0.548; rank variable, HR, 95% CI: 7.08, 2.70-18.56; I²=46.5%, P_{heterogeneity}=0.154), CV mortality (continuous variable, HR, 95% CI: 1.33, 1.14-1.57; I²=0.0%, P_{heterogeneity}=0.435), myocardial infarction (continuous variable, HR, 95% CI: 1.23, 1.02-1.49; rank variable, HR, 95% CI: 1.49, 1.26-1.76; I²=0.7%, P_{heterogeneity}=0.402), and new-onset heart failure (rank variable, HR, 95% CI: 3.23, 1.32-7.87; I²=83.0%, P_{heterogeneity}=0.003).In conclusion, decreased TRAIL was negatively associated with all-cause mortality and increasedTRAIL-R2 was positively associated with all-cause mortality, CV mortality, myocardial infarction, and heart failure.