Abstract
Interleukin (IL-33) and the ST2 receptor are implicated in the pathogenesis of atherosclerosis. Soluble ST2 (sST2), which negatively regulates IL-33 signaling, is an established biomarker in coronary artery disease and heart failure. Here we aimed to investigate the association of sST2 with carotid atherosclerotic plaque morphology, symptom presentation, and the prognostic value of sST2 in patients undergoing carotid endarterectomy. A total of 170 consecutive patients with high-grade asymptomatic or symptomatic carotid artery stenosis undergoing carotid endarterectomy were included in the study. The patients were followed up for 10 years, and the primary endpoint was defined as a composite of adverse cardiovascular events and cardiovascular mortality, with all-cause mortality as the secondary endpoint. The baseline sST2 showed no association with carotid plaque morphology assessed using carotid duplex ultrasound (B 0.051, 95% CI -0.145-0.248, p = 0.609), nor with modified histological AHA classification based on morphological description following surgery (B -0.032, 95% CI -0.194-0.130, p = 0.698). Furthermore, sST2 was not associated with baseline clinical symptoms (B -0.105, 95% CI -0.432-0.214, p = 0.517). On the other hand, sST2 was an independent predictor for long-term adverse cardiovascular events after adjustment for age, sex, and coronary artery disease (HR 1.4, 95% CI 1.0-2.4, p = 0.048), but not for all-cause mortality (HR 1.2, 95% CI 0.8-1.7, p = 0.301). Patients with high baseline sST2 levels had a significantly higher adverse cardiovascular event rate as compared to patients with lower sST2 (log-rank p < 0.001). Although IL-33 and ST2 play a role in the pathogenesis of atherosclerosis, sST2 is not associated with carotid plaque morphology. However, sST2 is an excellent prognostic marker for long-term adverse cardiovascular outcomes in patients with high-grade carotid artery stenosis.