Elevated FURIN levels in predicting mortality and cardiovascular events in patients with acute myocardial infarction.

OBJECTIVES: Proprotein convertase subtilisin/kexin (PCSK) family member 3 (FURIN) has been suggested to be involved in the development of atherosclerosis. The aim of this study was to investigate the prognostic implication of FURIN in patients after acute myocardial infarction (AMI). METHODS: This prospective study analyzed data from a total of 1312 consecutive patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction from August 2013 to June 2016. FURIN levels were analyzed in plasma obtained from AMI patients. RESULTS: The study included 1312 AMI patients. The patient population was predominantly male (63%) with a median age of 66 years (IQR: 19 years), and 59% were STEMI patients. During a follow-up of 2 years, 117 patients died, and 377 patients reached the combined endpoints of major adverse cardiac events (MACE). Patients with elevated FURIN levels had increased risk of MACE, all-cause mortality, recurrent MI and hospitalization for HF (log-rank test, p < 0.0001). After adjusting for clinical risk factors and established markers, the association of FURIN concentrations with the risk of MACE and its individual components and cardiovascular death was statistically significant in the higher tertile of FURIN concentrations. After the addition of FURIN to the models, FURIN showed additive prognostic significance for 2-year clinical outcomes. Variable importance plots of the models showed that FURIN was of high importance to predict both occurrence of MACE and all-cause mortality. CONCLUSIONS: We found that FURIN was associated with all-cause mortality and recurrent cardiovascular events in AMI patients independent of conventional risk factors and established markers.

Prognostic Utility of Soluble TREM-1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be critical for inflammatory signal amplification and involved in the development of atherosclerosis. TREM-1 is significantly increased in patients with myocardial infarction. The aim of this study was to investigate the association between soluble TREM-1 (sTREM-1) and mortality and cardiovascular events in patients with acute myocardial infarction. METHODS AND RESULTS: We included 838 consecutive patients with acute myocardial infarction from October 7, 2012 to December 5, 2014. Blood samples were collected from patients with acute myocardial infarction immediately after diagnosis. During follow-up, 88 patients died, and 180 patients reached the combined end points of major adverse cardiovascular event (MACE). Patients with high sTREM-1 (higher than the median) had increased risk of all-cause mortality and MACE compared with those with low sTREM-1 (log-rank test, P<0.001). After adjustment for confounding risk factors by Cox regression analysis, high sTREM-1 remained an independent predictor of all-cause mortality (hazard ratio, 1.978; 95% confidence interval, 1.462-2.675; P<0.001) and MACE (hazard ratio, 2.413; 95% confidence interval, 2.022-2.879; P<0.001). After the addition of sTREM-1 to the reference model, the C-statistic for all-cause mortality increased from 0.86 to 0.89, and the difference was 0.023 (95% confidence interval, 0.0009-0.0477), and the C-statistic for MACE increased from 0.71 to 0.80, and the difference was 0.087 (95% confidence interval, 0.053-0.122). sTREM-1 levels were consistently positively associated with risks of all-cause mortality and MACE in various subpopulations, and there was no significant interaction among prespecified subgroups. CONCLUSIONS: sTREM-1 was significantly associated with all-cause mortality and MACE, independent of established conventional risk factors in patients with acute myocardial infarction.