Plasma soluble TREM-1 and risk of cardiovascular disease in the population. Results from the Paris Prospective Study III and the CoLaus|PsyCoLaus.

AIMS: We examined the predictive value of soluble levels of triggering receptor expressed on myeloid cells 1 (sTREM-1) for incident cardiovascular disease (CVD). METHODS: The main analysis was conducted in an observational prospective cohort. Adjudicated CVD events included coronary heart disease, stroke, heart failure and peripheral artery disease. sTREM-1 measures were centralized using a protocol optimized for Meso Scale Discovery technology. RESULTS: Among 9097 CVD-free participants (39% females, mean age 59.6±6.3 years), median sTREM-1 concentration was 193.41 pg/mL (IQR= 158.13 to 241.54) at baseline (2008 to 2012). Over 10.1 years of median follow-up (IQR= 9.2 to 12.0), 444 participants experienced 479 CVD events. Higher sTREM-1 concentrations were associated with higher risk of CVD in multivariable Cox proportional hazard model (HR 200-290 vs. <200pg/ml= 4.25;95% CI:3.20 to 5.63 and HR >290 vs. <200pg/ml=10.40;95% CI:7.72 to 14.02). Results were consistent across CVD subtypes. Adding sTREM-1 to SCORE2-SCORE2 OP improved the Harell-C index (C-index 0.79 vs. 0.71; bootstrapped C index difference: 0.084; 95% CI: 0.083 to 0.085) overall including among individuals at low to moderate 10-year risk of CHD or stroke, and reclassification: categorical NRI: 0.34; 95% CI: 0.28 to 0.40. Findings were similar with other recommended risk scores. CONCLUSIONS: In this prospective study, higher circulating sTREM-1 levels were independently associated with incident CVD. Addition of sTREM-1 to established risk scores was associated with improvements in discrimination and reclassification metrics, supporting its potential relevance as a candidate biomarker for further evaluation in primary prevention.