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.