Plasma Sestrin2 levels and risk of acute ischemic stroke: A case–control study

Sestrin2, a stress-inducible protein with antioxidant properties, is upregulated in response to various stressors, including oxidative and energetic stress. This study examines the relationship between plasma Sestrin2 levels, total antioxidant capacity (TAC), total nitric oxide (NO), and the likelihood of experiencing an acute ischemic stroke (AIS) within the Qatari population. The cohort consisted of 187 AIS patients and 30 healthy controls. Plasma concentrations of Sestrin2, TAC, and nitrite/nitrate (an indirect measure of NO) were evaluated at four intervals: within 48 hours of stroke onset, and at 5 days, 30 days, and 1 year post-stroke. At stroke onset, AIS patients exhibited significantly lower plasma levels of Sestrin2 (1.434±3.57 vs. 8.383±7.39; p <0.001), TAC (1.88±0.42 vs. 2.279±0.326; p <0.001), and nitrite/nitrate (53.5±47.9 vs. 65.951±44.07; p = 0.04) compared to controls. Sestrin2 levels remained diminished at 5 and 30 days post-stroke, while NO levels increased by day 5 (p = 0.01). Multiple logistic regression analysis revealed that male sex, diabetes, high National Institutes of Health Stroke Scale (NIHSS) scores, and small vessel disease (SVD) were associated with increased odds of AIS, whereas Middle Eastern ethnicity correlated with reduced odds. Notably, higher tertiles of Sestrin2, TAC, and NO were linked to decreased odds of AIS, with adjusted odds ratios of 0.123 (p < 0.001), 0.327 (p = 0.01), and 0.063 (p = 0.01), respectively. The observed lower plasma levels of Sestrin2, TAC, and NO at stroke onset and up to 30 days post-event suggest their potential role as biomarkers in stroke occurrence and recovery, with elevated levels associated with a decreased likelihood of AIS.