Early Statin Use is Associated with Increased Risk of Infection After Stroke


      Infection after stroke is common and likely detrimental. Given the potent immunomodulatory properties of statins, we hypothesized that early statin use might increase the risk of infection in the immediate post stroke period.


      In a study cohort of 112 patients with ischemic stroke, we assessed the impact of early statin use on the risk of post stroke infection.


      After controlling for stroke severity and patient age, the odds ratio (OR) and 95% confidence interval (CI) for infection in the first 15 days after stroke among patients on a statin by day 3 after stroke was 7.21 (95% CI 1.40-37.98; P = .018). When controlling for univariate predictors of infection, the OR associated for infection associated with statin use actually increased, but was no longer significant (8.49 [95% CI 0.92-77.98]; P = .059). In addition, early statin use was associated with an increase in plasma interleukin-1 receptor antagonist (IL-1ra); IL-1ra was significantly higher in early statin users than in nonstatin users by day 7 after stroke.


      Our data suggest that early statin use appears to be associated with and increased risk of post stroke infection. This risk may, in part, be related to increases in plasma IL-1ra. If these findings are replicated in larger studies, they could have important implications for the timing of statin therapy after stroke.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Aslanyan S.
        • Weir C.J.
        • Diener H.C.
        • et al.
        Pneumonia and urinary tract infection after acute ischaemic stroke: A tertiary analysis of the gain international trial.
        Eur J Neurol. 2004; 11: 49-53
        • Hong K.S.
        • Kang D.W.
        • Koo J.S.
        • et al.
        Impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke.
        Eur J Neurol. 2008; 15: 1324-1331
        • Vermeij F.H.
        • Scholte op Reimer W.J.
        • de Man P.
        • et al.
        Stroke-associated infection is an independent risk factor for poor outcome after acute ischemic stroke: Data from the Netherlands stroke survey.
        Cerebrovasc Dis. 2009; 27: 465-471
        • Indredavik B.
        • Rohweder G.
        • Naalsund E.
        • et al.
        Medical complications in a comprehensive stroke unit and an early supported discharge service.
        Stroke. 2008; 39: 414-420
        • Walter U.
        • Knoblich R.
        • Steinhagen V.
        • et al.
        Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit.
        J Neurol. 2007; 254: 1323-1329
        • Tanzi P.
        • Cain K.
        • Kalil A.
        • et al.
        Post-stroke infection: A role for il-1ra?.
        Neurocrit Care. 2011; 14: 244-252
        • Prass K.
        • Meisel C.
        • Hoflich C.
        • et al.
        Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.
        J Exp Med. 2003; 198: 725-736
        • Hug A.
        • Dalpke A.
        • Wieczorek N.
        • et al.
        Infarct volume is a major determiner of post-stroke immune cell function and susceptibility to infection.
        Stroke. 2009; 40: 3226-3232
        • Haeusler K.G.
        • Schmidt W.U.
        • Fohring F.
        • et al.
        Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans.
        Cerebrovasc Dis. 2008; 25: 50-58
        • Adams Jr., H.P.
        • del Zoppo G.
        • Alberts M.J.
        • et al.
        Guidelines for the early management of adults with ischemic stroke: A guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
        Stroke. 2007; 38: 1655-1711
      1. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial.
        Lancet. 2002; 360: 7-22
        • Amarenco P.
        • Goldstein L.B.
        • Szarek M.
        • et al.
        Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.
        Stroke. 2007; 38: 3198-3204
        • Ovbiagele B.
        • Schwamm L.H.
        • Smith E.E.
        • et al.
        Recent nationwide trends in discharge statin treatment of hospitalized patients with stroke.
        Stroke. 2010; 41: 1508-1513
        • Marti-Fabregas J.
        • Gomis M.
        • Arboix A.
        • et al.
        Favorable outcome of ischemic stroke in patients pretreated with statins.
        Stroke. 2004; 35: 1117-1121
        • Sims J.R.
        • Gharai L.R.
        • Schaefer P.W.
        • et al.
        ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes.
        Neurology. 2009; 72: 2104-2110
        • Greenwood J.
        • Steinman L.
        • Zamvil S.S.
        Statin therapy and autoimmune disease: From protein prenylation to immunomodulation.
        Nat Rev Immunol. 2006; 6: 358-370
        • Montaner J.
        • Chacon P.
        • Krupinski J.
        • et al.
        Simvastatin in the acute phase of ischemic stroke: A safety and efficacy pilot trial.
        Eur J Neurol. 2008; 15: 82-90
        • Methe H.
        • Kim J.O.
        • Kofler S.
        • et al.
        Statins decrease toll-like receptor 4 expression and downstream signaling in human CD14+ monocytes.
        Arterioscler Thromb Vasc Biol. 2005; 25: 1439-1445
        • Bessler H.
        • Salman H.
        • Bergman M.
        • et al.
        In vitro effect of statins on cytokine production and mitogen response of human peripheral blood mononuclear cells.
        Clin Immunol. 2005; 117: 73-77
        • Ascer E.
        • Bertolami M.C.
        • Venturinelli M.L.
        • et al.
        Atorvastatin reduces proinflammatory markers in hypercholesterolemic patients.
        Atherosclerosis. 2004; 177: 161-166
        • Ferro D.
        • Parrotto S.
        • Basili S.
        • et al.
        Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia.
        J Am Coll Cardiol. 2000; 36: 427-431
        • Kishimoto T.
        IL-6: From its discovery to clinical applications.
        Int Immunol. 2010; 22: 347-352
        • Chamorro A.
        • Amaro S.
        • Vargas M.
        • et al.
        Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke.
        J Neurol Neurosurg Psychiatry. 2006; 77: 1279-1281
        • de Bont N.
        • Netea M.G.
        • Rovers C.
        • et al.
        LPS-induced release of IL-1 beta, IL-1ra, IL-6, and TNF-alpha in whole blood from patients with familial hypercholesterolemia: No effect of cholesterol-lowering treatment.
        J Interferon Cytokine Res. 2006; 26: 101-107
        • Fuentes B.
        • Martinez-Sanchez P.
        • Diez-Tejedor E.
        Lipid-lowering drugs in ischemic stroke prevention and their influence on acute stroke outcome.
        Cerebrovasc Dis. 2009; 27: 126-133
        • Cubeddu L.X.
        • Seamon M.J.
        Statin withdrawal: Clinical implications and molecular mechanisms.
        Pharmacotherapy. 2006; 26: 1288-1296
        • Endres M.
        • Laufs U.
        Discontinuation of statin treatment in stroke patients.
        Stroke. 2006; 37: 2640-2643
        • Blanco M.
        • Nombela F.
        • Castellanos M.
        • et al.
        Statin treatment withdrawal in ischemic stroke: A controlled randomized study.
        Neurology. 2007; 69: 904-910
        • Janda S.
        • Young A.
        • Fitzgerald J.M.
        • et al.
        The effect of statins on mortality from severe infections and sepsis: A systematic review and meta-analysis.
        J Crit Care. 2010; 25: 656.e7-656.e22
        • Kruger P.S.
        • Harward M.L.
        • Jones M.A.
        • et al.
        Continuation of statin therapy in patients with presumed infection: A randomized controlled trial.
        Am J Respir Crit Care Med. 2011; 183: 774-781
        • Collins R.
        • Armitage J.
        • Parish S.
        • et al.
        Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions.
        Lancet. 2004; 363: 757-767
        • Amarenco P.
        • Bogousslavsky J.
        • Callahan 3rd, A.
        • et al.
        High-dose atorvastatin after stroke or transient ischemic attack.
        N Engl J Med. 2006; 355: 549-559