Background <p>Plaque destabilization and rupture are the primary triggers of acute coronary syndrome (ACS). Soluble growth stimulation expressed gene 2 (sST2) has been implicated in cardiovascular disease. We aimed to investigate the association between circulating sST2 levels and features of coronary plaque destabilization assessed by optical coherence tomography (OCT) in patients with unstable angina (UA).</p> Methods <p>This study enrolled 122 patients admitted with UA and 107 age- and sex-matched healthy controls. All UA patients underwent standard coronary angiography and OCT imaging to identify features indicative of plaque destabilization. Plasma sST2 levels were measured in all participants using an immunofluorescence assay. Associations between sST2 levels, clinical characteristics, and factors predicting OCT-defined plaque destabilization were analyzed.</p> Results <p>sST2 levels were significantly higher in UA patients compared to healthy controls (<i>p</i> &lt; 0.001). Among UA patients, sST2 levels were significantly elevated in those with OCT-defined plaque destabilization features compared to those without (<i>p</i> &lt; 0.001). In multivariable logistic regression analysis, elevated sST2 levels emerged as an independent factor associated with the presence of OCT-defined plaque destabilization (<i>p</i> = 0.013).</p> Conclusions <p>Circulating sST2 levels are elevated in UA patients and independently associated with features of coronary plaque destabilization identified by OCT. These findings suggest sST2 may be a novel biomarker reflecting plaque destabilization in patients with UA, potentially aiding in risk stratification.</p>