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Abstract
In a murine model of acute ischemic stroke, SIRT6 knockdown resulted in larger cerebral infarct size, worse neurological outcome, and higher mortality, indicating a possible neuro-protective role of SIRT6. In this study, we aimed at evaluating the prognostic value of serum SIRT6 levels in patients with acute ischemic stroke (AIS). Serum levels of SIRT6, collected within 72 h from symptom-onset, were measured in 317 consecutively enrolled AIS patients from the COSMOS cohort. The primary endpoint of this analysis was 90-day mortality. The independent prognostic value of SIRT6 was assessed with multivariate logistic and Cox proportional regression models. 35 patients (11%) deceased within 90-day follow-up. After adjustment for established risk factors (age, NIHSS, heart failure, atrial fibrillation, and C reactive protein), SIRT6 levels were negatively associated with mortality. The optimal cut-off for survival was 634 pg/mL. Patients with SIRT6 levels below this threshold had a higher risk of death in multivariable Cox regression. In this pilot study, SIRT6 levels were significantly associated with 90-day mortality after AIS; these results build on previous molecular and causal observations made in animal models. Should this association be confirmed, SIRT6 could be a potential prognostic predictor and therapeutic target in AIS.
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1 University of Genoa, First Clinic of Internal Medicine, Department of Internal Medicine, Genoa, Italy (GRID:grid.5606.5) (ISNI:0000 0001 2151 3065); IRCCS Ospedale Policlinico San Martino Genoa–Italian Cardiovascular Network, Genoa, Italy (GRID:grid.410345.7) (ISNI:0000 0004 1756 7871)
2 University of Zurich, Center for Molecular Cardiology, Schlieren, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650); University of Perugia, Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and Surgery, Perugia, Italy (GRID:grid.9027.c) (ISNI:0000 0004 1757 3630)
3 University Hospital and University of Zurich, Department of Neurology, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650)
4 University of Zurich, Center for Molecular Cardiology, Schlieren, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650)
5 University Hospital of Basel, Department of Endocrinology, Basel, Switzerland (GRID:grid.410567.1)
6 University of Zurich, Center for Molecular Cardiology, Schlieren, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650); University Hospital Zurich, University Heart Center, Department of Cardiology, Zurich, Switzerland (GRID:grid.412004.3) (ISNI:0000 0004 0478 9977); University Hospital Zurich, Department of Research and Education, Zurich, Switzerland (GRID:grid.412004.3) (ISNI:0000 0004 0478 9977)
7 University Hospital and University of Zurich, Department of Neurology, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650); Department of Neurology University Hospital of Basel, Basel, Switzerland (GRID:grid.410567.1)