Plasma levels of sTREM2 in chronic heart failure: predictors and prognostic relevance

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on myeloid cells, including macrophages and microglia, and is involved in modulating inflammation and lipid metabolism. Elevated plasma levels of soluble TREM2 (sTREM2) have been associated with heart failure (HF) and neurodegenerative diseases, such as Alzheimer's disease (AD). This post hoc analysis explored the association of plasma sTREM2 with cognition and mortality in the Cognition.Matters-HF cohort of 148 patients with chronic HF. Plasma sTREM2 levels were measured using a bead-based immunoassay, and the cohort was split into high and low sTREM2 groups based on a median concentration of 16.6 ng/mL. Higher sTREM2 levels were associated with worse cognitive performance, particularly in working memory (<i>T</i> = -2.67, <i>P</i> = 0.009) and visual/verbal memory (<i>T</i> = -2.16, <i>P</i> = 0.032), but not with cardiac function. In univariate Cox regression, a higher plasma sTREM2 concentration was linked to increased mortality (HR = 1.28, 95% CI 1.05-1.57, <i>P</i> = 0.015), although this association did not remain significant after adjusting for age and heart failure severity (adjusted HR = 0.95, 95% CI 0.70-1.28, <i>P</i> = 0.720). These findings suggest that plasma sTREM2 reflects cognitive impairment more than cardiac dysfunction in HF, highlighting its potential as a biomarker for neuroinflammation in patients with HF.<b>NEW & NOTEWORTHY</b> This study establishes a significant association between elevated plasma sTREM2 levels and cognitive impairment in chronic patients with heart failure (HF), particularly in working memory and attention. Although higher sTREM2 levels correlated with worse survival in unadjusted analyses, they did not emerge as independent predictors of mortality once adjustments had been made for age and heart failure severity. These findings suggest that plasma sTREM2 may serve as a valuable biomarker for detecting HF-related mild cognitive impairment.