Jonathan Golledge1, Paula Clancy, Jane Maguire, Lisa Lincz, Simon Koblar, Mark McEvoy, John Attia, Chris Levi, Jonathan Sturm, Osvaldo P Almeida, Bu B Yeap, Leon Flicker, Paul E Norman, Graeme J Hankey. 1. From the Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Australia (J.G., P.C.); Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Australia (J.G.); Faculty of Health and Medicine, School of Nursing and Midwifery (J.M.) and Faculty of Health, School of Health Sciences (C.L., J.S.), The University of Newcastle, Newcastle, Australia; The Hunter Medical Research Institute, Newcastle, New South Wales, Australia (J.M., L.L., M.M., J.A.); Hunter Haematology Research Group, Calvary Mater Newcastle, Waratah, New South Wales, Australia (L.L.); Stroke Research Programme, University of Adelaide, The Queen Elizabeth Hospital campus, Adelaide, Australia (S.K.); The Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, New South Wales, Australia (M.M., J.A.); Department of Neurosciences, Central Coast Health District, Gosford, New South Wales, Australia (J.S.); School of Psychiatry and Clinical Neurosciences (O.P.A.), School of Medicine and Pharmacology (B.B.Y.), Western Australian Centre for Health and Ageing, Centre for Medical Research (L.F.), School of Surgery (P.E.N.), and School of Medicine and Pharmacology (G.J.H.), University of Western Australia, Perth, Western Australia, Australia; and Department of Endocrinology and Diabetes, Fremantle Hospital, Fremantle, Australia (B.B.Y.).
Abstract
BACKGROUND AND PURPOSE: Studies in rodent models suggest that upregulating angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to assess the association of plasma Angpt1 with stroke occurrence and outcome. METHODS: Plasma Angpt1 was measured in 336 patients who had experienced a recent stroke and 321 healthy controls with no stroke history. Patients with stroke (n=285) were reassessed at 3 months and plasma Angpt1 concentration on admission compared between those with severe and minor disability as assessed by the modified Rankin scale. In a separate cohort of 4032 community-acquired older men prospectively followed for a minimum of 6 years, the association of plasma Angpt1 with stroke incidence was examined. RESULTS: Median plasma Angpt1 was 3-fold lower in patients who had experienced a recent stroke (6.42, interquartile range, 4.26-9.53 compared with 17.36; interquartile range, 14.01-22.46 ng/mL; P<0.001) and remained associated with stroke after adjustment for other risk factors. Plasma Angpt1 concentrations on admission were lower in patients who had severe disability or died at 3 months (median, 5.52; interquartile range, 3.81-8.75 ng/mL for modified Rankin scale 3-6; n=91) compared with those with minor disability (median, 7.04; interquartile range, 4.75-9.92 ng/mL for modified Rankin scale 0-2; n=194), P=0.012, and remained negatively associated with severe disability or death after adjusting for other risk factors. Plasma Angpt1 was not predictive of stroke incidence in community-dwelling older men. CONCLUSIONS: Plasma Angpt1 concentrations are low after ischemic stroke particularly in patients with poor stroke outcomes at 3 months. Interventions effective at upregulating Angpt1 could potentially improve stroke outcomes.
BACKGROUND AND PURPOSE: Studies in rodent models suggest that upregulating angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to assess the association of plasma Angpt1 with stroke occurrence and outcome. METHODS: Plasma Angpt1 was measured in 336 patients who had experienced a recent stroke and 321 healthy controls with no stroke history. Patients with stroke (n=285) were reassessed at 3 months and plasma Angpt1 concentration on admission compared between those with severe and minor disability as assessed by the modified Rankin scale. In a separate cohort of 4032 community-acquired older men prospectively followed for a minimum of 6 years, the association of plasma Angpt1 with stroke incidence was examined. RESULTS: Median plasma Angpt1 was 3-fold lower in patients who had experienced a recent stroke (6.42, interquartile range, 4.26-9.53 compared with 17.36; interquartile range, 14.01-22.46 ng/mL; P<0.001) and remained associated with stroke after adjustment for other risk factors. Plasma Angpt1 concentrations on admission were lower in patients who had severe disability or died at 3 months (median, 5.52; interquartile range, 3.81-8.75 ng/mL for modified Rankin scale 3-6; n=91) compared with those with minor disability (median, 7.04; interquartile range, 4.75-9.92 ng/mL for modified Rankin scale 0-2; n=194), P=0.012, and remained negatively associated with severe disability or death after adjusting for other risk factors. Plasma Angpt1 was not predictive of stroke incidence in community-dwelling older men. CONCLUSIONS: Plasma Angpt1 concentrations are low after ischemic stroke particularly in patients with poor stroke outcomes at 3 months. Interventions effective at upregulating Angpt1 could potentially improve stroke outcomes.
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