High Plasma Levels of Sestrin2 Are Associated with Cardiovascular Events in Patients Undergoing Coronary Angiography

Atherosclerotic diseases, like coronary artery disease (CAD), are recognized to be associated with oxidative stress and inflammation. Sestrin2 is a stress-inducible protein that has anti-oxidant and anti-inflammatory properties. We previously reported that plasma sestrin2 levels were high in patients with CAD. However, no study has shown their prognostic value in patients with CAD. We investigated the association between plasma sestrin2 levels and major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, unstable angina, coronary revascularization, heart failure, or stroke) in 320 patients undergoing coronary angiography, of whom 191 had CAD. During a mean follow-up of 7.0 ± 4.2 years, 58 patients had MACE. Plasma sestrin2 levels were higher in patients with CAD than without CAD (median 16.4 versus 14.2 ng/mL, P < 0.05). Notably, patients with MACE had higher sestrin2 levels (19.5 versus 14.9 ng/mL) and more often had sestrin2 > 15.0 ng/mL (79% versus 49%) than those without MACE (P < 0.001). Kaplan-Meier analysis showed lower event-free survival in patients with sestrin2 > 15.0 ng/mL than in those with ≤ 15.0 ng/mL (P < 0.001). In multivariate Cox hazards analysis, sestrin2 level (> 15.0 ng/mL) was a significant predictor of MACE (hazard ratio: 2.44; 95%CI: 1.28-4.67), independent of CAD and atherosclerotic risk factors. Moreover, among 191 patients with CAD, sestrin2 level was also a significant predictor of MACE (hazard ratio: 2.51; 95%CI: 1.28-4.82), independent of the severity of CAD and coronary revascularization. Thus, high plasma levels of sestrin2 at baseline angiography were found to be associated with an increased risk of cardiovascular events in patients with CAD and patients undergoing coronary angiography.