2006;47:1108 1116. 794. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291:565 575. 795. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lower- ing with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567 1577. 796. Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40:1365 1372. 797. Marcovina SM, Koschinsky ML. Evaluation of lipoprotein(a) as a pro- thrombotic factor: progress from bench to bedside. Curr Opin Lipidol. 2003;14:361 366. 798. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation. 2000;102:1082 1085. 799. Foody JM, Milberg JA, Pearce GL, Sprecher DL. Lipoprotein(a) associ- ated with coronary artery disease in older women: age and gender analy- sis. Atherosclerosis. 2000;153:445 451. 800. Hancock MA, Boffa MB, Marcovina SM, Nesheim ME, Koschinsky ML. Inhibition of plasminogen activation by lipoprotein(a): critical domains in apolipoprotein(a) and mechanism of inhibition on fibrin and degraded fibrin surfaces. J Biol Chem. 2003;278:23260 23269. 801. Ariyo AA, Thach C, Tracy R; Cardiovascular Health Study Investigators. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. N Engl J Med. 2003;349:2108 2115. 802. Milionis HJ, Filippatos TD, Loukas T, Bairaktari ET, Tselepis AD, Elisaf MS. Serum lipoprotein(a) levels and apolipoprotein(a) isoform size and risk for first-ever acute ischaemic nonembolic stroke in elderly individu- als. Atherosclerosis. 2006;187:170 176. 803. Ohira T, Schreiner PJ, Morrisett JD, Chambless LE, Rosamond WD, Folsom AR. Lipoprotein(a) and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2006;37:1407 1412. 804. Ridker PM, Stampfer MJ, Hennekens CH. Plasma concentration of lipoprotein(a) and the risk of future stroke. JAMA. 1995;273:1269 1273. 805. Virani SS, Brautbar A, Davis BC, Nambi V, Hoogeveen RC, Sharrett AR, Coresh J, Mosley TH, Morrisett JD, Catellier DJ, Folsom AR, Boerwinkle E, Ballantyne CM. Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2012;125:241 249. 806. Klein JH, Hegele RA, Hackam DG, Koschinsky ML, Huff MW, Spence JD. Lipoprotein(a) is associated differentially with carotid ste- nosis, occlusion, and total plaque area. Arterioscler Thromb Vasc Biol. 2008;28:1851 1856. 807. Willeit J, Kiechl S, Santer P, Oberhollenzer F, Egger G, Jarosch E, Mair A. Lipoprotein(a) and asymptomatic carotid artery disease: evidence of a prominent role in the evolution of advanced carotid plaques: the Bruneck Study. Stroke. 1995;26:1582 1587. 808. Cerrato P, Imperiale D, Fornengo P, Bruno G, Cassader M, Maffeis P, Cavallo Perin P, Pagano G, Bergamasco B. Higher lipoprotein (a) lev- els in atherothrombotic than lacunar ischemic cerebrovascular disease. Neurology. 2002;58:653 655. 809. Smolders B, Lemmens R, Thijs V. Lipoprotein (a) and stroke: a meta- analysis of observational studies. Stroke. 2007;38:1959 1966. 810. Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, Pennells L, Kaptoge S, Caslake M, Thompson A, Butterworth AS, Sarwar N, Wormser D, Saleheen D, Ballantyne CM, Psaty BM, Sundstrom J, Ridker PM, Nagel D, Gillum RF, Ford I, Ducimetiere P, Kiechl S, Koenig W, Dullaart RP, Assmann G, D Agostino RB Sr, Dagenais GR, Cooper JA, Kromhout D, Onat A, Tipping RW, Gomez- de-la-Camara A, Rosengren A, Sutherland SE, Gallacher J, Fowkes FG, Casiglia E, Hofman A, Salomaa V, Barrett-Connor E, Clarke R, Brunner E, Jukema JW, Simons LA, Sandhu M, Wareham NJ, Khaw KT, Kauhanen J, Salonen JT, Howard WJ, Nordestgaard BG, Wood AM, Thompson SG, Boekholdt SM, Sattar N, Packard C, Gudnason V, Danesh J. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307:2499 2506. 811. Kenet G, Lutkhoff LK, Albisetti M, Bernard T, Bonduel M, Brandao L, Chabrier S, ChanA, deVeber G, Fiedler B, Fullerton HJ, Goldenberg NA, Grabowski E, Gunther G, Heller C, Holzhauer S, Iorio A, Journeycake J, Junker R, Kirkham FJ, Kurnik K, Lynch JK, Male C, Manco-Johnson M, Mesters R, Monagle P, van Ommen CH, Raffini L, Rostasy K, Simioni P, Strater RD,Young G, Nowak-Gottl U. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation. 2010;121:1838 1847. 812. Goldenberg NA, Bernard TJ, Hillhouse J, Armstrong-Wells J, Galinkin J, Knapp-Clevenger R, Jacobson L, Marcovina S, Manco-Johnson MJ. Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children. Haematologica. 2013;98:802 807. 813. Nordestgaard BG, Chapman MJ, Ray K, Boren J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgozoglu L, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844 2853. 814. Anticardiolipin antibodies are an independent risk factor for first isch- emic stroke: the Antiphospholipid Antibodies in Stroke Study (APASS) Group. Neurology. 1993;43:2069 2073. 815. Dragoni F, Chiarotti F, Rosano G, Simioni P, Tormene D, Mazzucconi MG, Cafolla A, Avvisati G. Thrombophilic screening in young patients (<40 years) with idiopathic ischemic stroke: a controlled study. Thromb Res. 2011;127:85 90. 816. Erkan D, Harrison MJ, Levy R, Peterson M, Petri M, Sammaritano L, Unalp-Arida A, Vilela V, Yazici Y, Lockshin MD. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum. 2007;56:2382 2391. Meschia et al Guidelines for the Primary Prevention of Stroke 3829 817. Frances C, Papo T, Wechsler B, Laporte JL, Biousse V, Piette JC. Sneddon syndrome with or without antiphospholipid antibod- ies: a comparative study in 46 patients. Medicine (Baltimore). 1999;78:209 219. 818. Ginsburg KS, Liang MH, Newcomer L, Goldhaber SZ, Schur PH, Hennekens CH, Stampfer MJ. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992;117:997 1002. 819. Brey RL, Abbott RD, Curb JD, Sharp DS, Ross GW, Stallworth CL, Kittner SJ. Beta(2)-glycoprotein 1-dependent anticardiolipin antibod- ies and risk of ischemic stroke and myocardial infarction: the Honolulu Heart Program. Stroke. 2001;32:1701 1706. 820. JanardhanV, Wolf PA, Kase CS, Massaro JM, D Agostino RB, Franzblau C, Wilson PW. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study. Stroke. 2004;35:736 741. 821. Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphos- pholipid syndrome. Blood. 2003;102:2717 2723. 822. Heinzlef O, Abuaf N, Cohen A, Amarenco P; French Study of Aortic Plaques in Stroke Group. Recurrent stroke and vascular events in elderly patients with anticardiolipin antibodies: a prospective study. J Neurol. 2001;248:373 379. 823. PengoV, RuffattiA, Legnani C, Testa S, Fierro T, Marongiu F, De Micheli V, Gresele P, Tonello M, Ghirarduzzi A, Bison E, Denas G, Banzato A, Padayattil Jose S, Iliceto S. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011;118:4714 4718. 824. Ruffatti A, Del Ross T, Ciprian M, Bertero MT, Sciascia S, Scarpato S, Montecucco C, Rossi S, Caramaschi P, Biasi D, Doria A, Rampudda M, Monica N, Fischetti F, Picillo U, Brucato A, Salvan E, Vittorio P, Meroni P, Tincani A; Antiphospholipid Syndrome Study Group of Italian Society of Rheumatology. Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study. Ann Rheum Dis. 2011;70:1083 1086. 825. Petri M. Management of thrombosis in antiphospholipid antibody syn- drome. Rheum Dis Clin North Am. 2001;27:633 642, viii. 826. Chan M, Becker RC, Shah SH, Levine SR. Coagulopathy and stroke. In: Goldstein LB, ed. A Primer on Stroke Prevention and Treatment: an Overview Based on AHA/ASA Guidelines. Oxford, UK: Wiley- Blackwell; 2009:152 169. 827. Pezzini A, Del Zotto E, Magoni M, Costa A, Archetti S, Grassi M, Akkawi NM, Albertini A, Assanelli D, Vignolo LA, Padovani A. Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke. 2003;34:28 33. 828. Bank I, Libourel EJ, Middeldorp S, Van Pampus EC, Koopman MM, Hamulyak K, Prins MH, Van Der Meer J, Buller HR. Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study. Arch Intern Med. 2004;164:1932 1937. 829. Barnes C, Deveber G. Prothrombotic abnormalities in childhood isch- aemic stroke. Thromb Res. 2006;118:67 74. 830. Dalen JE. Should patients with venous thromboembolism be screened for thrombophilia? Am J Med. 2008;121:458 463. 831. Hamedani AG, Cole JW, Mitchell BD, Kittner SJ. Meta-analysis of fac- tor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke. 2010;41:1599 1603. 832. Wasay M, Bakshi R, Bobustuc G, Kojan S, Sheikh Z, Dai A, Cheema Z. Cerebral venous thrombosis: analysis of a multicenter cohort from the United States. J Stroke Cerebrovasc Dis. 2008;17:49 54. 833. Wu O, Robertson L, Twaddle S, Lowe GD, Clark P, Greaves M, Walker ID, Langhorne P, Brenkel I, Regan L, Greer I. Screening for throm- bophilia in high-risk situations: systematic review and cost-effective- ness analysis: the Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess. 2006;10:1 110. 834. Wells PS, Louzada ML, Taljaard M, Anderson DR, Kahn SR, Langlois NJ, Rutberg J, Kovacs MJ, Rodger MA. A pilot study to assess the feasibility of a multicenter cluster randomized trial for the manage- ment of asymptomatic persons with a thrombophilia. J Genet Couns. 2009;18:475 482. 835. Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:2045 2051. 836. Kamel H, Iadecola C. Brain-immune interactions and ischemic stroke: clinical implications. Arch Neurol. 2012;69:576 581. 837. Oei HH, van der Meer IM, Hofman A, Koudstaal PJ, Stijnen T, Breteler MM, Witteman JC. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation. 2005;111:570 575. 838. Vittos O, Toana B, Vittos A, Moldoveanu E. Lipoprotein-associated phospholipase A2 (Lp-PLA2): a review of its role and significance as a cardiovascular biomarker. Biomarkers. 2012;17:289 302. 839. Nambi V, Hoogeveen RC, Chambless L, Hu Y, Bang H, Coresh J, Ni H, Boerwinkle E, Mosley T, Sharrett R, Folsom AR, Ballantyne CM. Lipoprotein-associated phospholipase A2 and high-sensitivity C-reactive protein improve the stratification of ischemic stroke risk in the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2009;40:376 381. 840. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and theAmerican HeartAssociation. Circulation. 2003;107:499 511. 841. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in appar- ently healthy men. N Engl J Med. 1997;336:973 979. 842. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98:731 733. 843. Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, D Agostino RB, Franzblau C, Wilson PW. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke. 2001;32:2575 2579. 844. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375:132 140. 845. Kjaergaard AD, Bojesen SE, Johansen JS, Nordestgaard BG. Elevated plasma YKL-40 levels and ischemic stroke in the general population. Ann Neurol. 2010;68:672 680. 846. Fischer LM, Schlienger RG, Matter C, Jick H, Meier CR. Effect of rheu- matoid arthritis or systemic lupus erythematosus on the risk of first-time acute myocardial infarction. Am J Cardiol. 2004;93:198 200. 847. Gabriel SE. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med. 2008;121(suppl 1):S9 S14. 848. Sodergren A, Stegmayr B, Lundberg V, Ohman ML, Wallberg-Jonsson S. Increased incidence of and impaired prognosis after acute myocardial infarction among patients with seropositive rheumatoid arthritis. Ann Rheum Dis. 2007;66:263 266. 849. Turesson C, Jarenros A, Jacobsson L. Increased incidence of cardiovas- cular disease in patients with rheumatoid arthritis: results from a com- munity based study. Ann Rheum Dis. 2004;63:952 955. 850. Wolfe F, Freundlich B, Straus WL. Increase in cardiovascular and cere- brovascular disease prevalence in rheumatoid arthritis. J Rheumatol. 2003;30:36 40. 851. Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011;7:399 408. 852. Lindhardsen J, Ahlehoff O, Gislason GH, Madsen OR, Olesen JB, Svendsen JH, Torp-Pedersen C, Hansen PR. Risk of atrial fibrillation and stroke in rheumatoid arthritis: Danish nationwide cohort study. BMJ. 2012;344:e1257. 853. Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Cote R, Grover SA, Fortin PR, Clarke AE, Senecal JL. Traditional Framingham risk factors fail to fully account for acceler- ated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001;44:2331 2337. 854. Manzi S, Selzer F, Sutton-Tyrrell K, Fitzgerald SG, Rairie JE, Tracy RP, Kuller LH. Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum. 1999;42:51 60. 855. Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, Sammaritano L, Devereux RB, Schwartz JE, Levine DM, Salmon JE. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med. 2006;144:249 256. 856. Salmon JE, Roman MJ. Subclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Am J Med. 2008;121(suppl 1):S3 S8. 857. Pearson TA. Heightened risk of cardiovascular disease in patients with rheumatoid arthritis: introduction. Am J Med. 2008;121:S1 S2. 858. Grau AJ, Urbanek C, Palm F. Common infections and the risk of stroke. Nat Rev Neurol. 2010;6:681 694. 859. Elkind MS, Ramakrishnan P, Moon YP, Boden-Albala B, Liu KM, Spitalnik SL, Rundek T, Sacco RL, Paik MC. Infectious burden and risk of stroke: the Northern Manhattan Study. Arch Neurol. 2010;67:33 38. 860. Elkind MS, Luna JM, Moon YP, Boden-Albala B, Liu KM, Spitalnik S, Rundek T, Sacco RL, Paik MC. Infectious burden and carotid plaque thickness: the Northern Manhattan Study. Stroke. 2010;41:e117-e122. 861. Cercek B, Shah PK, Noc M, Zahger D, Zeymer U, Matetzky S, Maurer G, Mahrer P; AZACS Investigators. Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet. 2003;361:809 813. 862. Zahn R, Schneider S, Frilling B, Seidl K, Tebbe U, Weber M, Gottwik M, Altmann E, Seidel F, Rox J, Hoffler U, Neuhaus KL, Senges J; Working Group of Leading Hospital Cardiologists. Antibiotic therapy after acute myocardial infarction: a prospective randomized study. Circulation. 2003;107:1253 1259. 863. Elkind MS, Carty CL, O Meara ES, Lumley T, Lefkowitz D, Kronmal RA, Longstreth WT Jr. Hospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study. Stroke. 2011;42:1851 1856. 864. Mamas MA, Fraser D, Neyses L. Cardiovascular manifestations associ- ated with influenza virus infection. Int J Cardiol. 2008;130:304 309. 865. Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis. 2009;9:601 610. 866. Madjid M, Curkendall S, Blumentals WA. The influence of oseltami- vir treatment on the risk of stroke after influenza infection. Cardiology. 2009;113:98 107. 867. Grau AJ, Fischer B, Barth C, Ling P, Lichy C, Buggle F. Influenza vaccination is associated with a reduced risk of stroke. Stroke. 2005;36:1501 1506. 868. Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M. Influenza vaccination and reduction in hospitalizations for cardiac dis- ease and stroke among the elderly. N Engl J Med. 2003;348:1322 1332. 869. Wang CS, Wang ST, Lai CT, Lin LJ, Chou P. Impact of influenza vacci- nation on major cause-specific mortality. Vaccine. 2007;25:1196 1203. 870. Johnstone J, Loeb M, Teo KK, Gao P, Dyal L, Liu L,AvezumA, Cardona- Munoz E, Sleight P, Fagard R, Yusuf S; Ongoing Telmisartan Alone and in Combination With Ramipril Global EndPoint Trial (ONTARGET); Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) Investigators. Influenza vaccination and major adverse vascular events in high-risk patients. Circulation. 2012;126:278 286. 871. Davis MM, Taubert K, Benin AL, Brown DW, Mensah GA, Baddour LM, Dunbar S, Krumholz HM; American Heart Association; American College of Cardiology. Influenza vaccination as secondary preven- tion for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology. Circulation. 2006;114:1549 1553. 872. De Berardis G, Lucisano G, D Ettorre A, Pellegrini F, Lepore V, Tognoni G, Nicolucci A. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA. 2012;307:2286 2294. 873. Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple pri- mary prevention trials of cardiovascular events using aspirin. Am J Cardiol. 2011;107:1796 1801. 874. Raju N, Sobieraj-Teague M, Hirsh J, O Donnell M, Eikelboom J. Effect of aspirin on mortality in the primary prevention of cardiovascular dis- ease. Am J Med. 2011;124:621 629. 875. Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collabora- tive meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849 1860. 876. US Preventive Services Task Force. Aspirin for the prevention of cardio- vascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150:396 404. 877. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr, Smith SC Jr, Stone NJ, Taubert KA. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update: consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases: American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002;106:388 391. 878. Hayden M, Pignone M, Phillips C, Mulrow C.Aspirin for the primary pre- vention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;136:161 172. 879. Collaborative overview of randomised trials of antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by prolonged anti- platelet therapy in various categories of patients: Antiplatelet Trialists Collaboration. BMJ. 1994;308:81 106. 880. Hart RG, Halperin JL, McBride R, Benavente O, Man-Son-Hing M, Kronmal RA. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses. Arch Neurol. 2000;57:326 332. 881. Robinson JG, Rahilly-Tierney C, Lawler E, Gaziano JM. Benefits associ- ated with achieving optimal risk factor levels for the primary prevention of cardiovascular disease in older men. J Clin Lipidol. 2012;6:58 65. 882. Soejima H, Ogawa H, Morimoto T, Nakayama M, Okada S, Uemura S, Kanauchi M, Doi N, Sakuma M, Jinnouchi H, Sugiyama S, Waki M, SaitoY; JPAD Trial Investigators. Aspirin reduces cerebrovascular events in type 2 diabetic patients with poorly controlled blood pressure: sub- analysis from the JPAD trial. Circ J. 2012;76:1526 1532. 883. Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R; Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptom- atic peripheral arterial disease. BMJ. 2008;337:a1840. 884. De Berardis G, Sacco M, Strippoli GF, Pellegrini F, Graziano G, Tognoni G, Nicolucci A. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ. 2009;339:b4531. 885. Calvin AD, Aggarwal NR, Murad MH, Shi Q, Elamin MB, Geske JB, Fernandez-Balsells MM, Albuquerque FN, Lampropulos JF, Erwin PJ, Smith SA, Montori VM. Aspirin for the primary prevention of cardiovas- cular events: a systematic review and meta-analysis comparing patients with and without diabetes. Diabetes Care. 2009;32:2300 2306. 886. Zhang C, Sun A, Zhang P, Wu C, Zhang S, Fu M, Wang K, Zou Y, Ge J. Aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract. 2010;87:211 218. 887. Stavrakis S, Stoner JA, Azar M, Wayangankar S, Thadani U. Low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Am J Med Sci. 2011;341:1 9. 888. Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010;121:2694 2701. 889. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352:1293 1304. 890. Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, Ganiats TG, Gomes AS, Gornik HL, Gracia C, Gulati M, Haan CK, Judelson DR, Keenan N, Kelepouris E, Michos ED, Newby LK, Oparil S, Ouyang P, Oz MC, Petitti D, Pinn VW, Redberg RF, Scott R, Sherif K, Smith SC Jr, Sopko G, Steinhorn RH, Stone NJ, Taubert KA, Todd BA, Urbina E, Wenger NK; Expert Panel/Writing Group; American Heart Association; American Academy of Family Physicians; American College of Obstetricians and Gynecologists; American College of Cardiology Foundation; Society of Thoracic Surgeons; American Medical Women's Association; Centers for Disease Control and Prevention; Office of Research on Women's Health; Association of Black Cardiologists; American College of Physicians; World Heart Federation; National Heart, Lung, and Blood Institute; American College of Nurse Practitioners. Evidence-based guidelines for cardiovascular disease pre- vention in women: 2007 update. Circulation. 2007;115:1481 1501. Meschia et al Guidelines for the Primary Prevention of Stroke 3831 891. Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD; Aspirin for Asymptomatic Atherosclerosis Trialists. Aspirin for preven- tion of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303:841 848. 892. Uchiyama S, Demaerschalk BM, Goto S, Shinohara Y, Gotoh F, Stone WM, Money SR, Kwon SU. Stroke prevention by cilostazol in patients with atherothrombosis: meta-analysis of placebo-controlled randomized trials. J Stroke Cerebrovasc Dis. 2009;18:482 490. 893. Jardine MJ, Ninomiya T, Perkovic V, Cass A, Turnbull F, Gallagher MP, Zoungas S, Lambers Heerspink HJ, Chalmers J, Zanchetti A. Aspirin is beneficial in hypertensive patients with chronic kidney disease: a post-hoc subgroup analysis of a randomized controlled trial. J Am Coll Cardiol. 2010;56:956 965. 894. Centers for Disease Control and Prevention. Emergency department vis- its within the past 12 months among adults aged 18 and over, by selected characteristics: United States, selected years 1997 2011. http://www. cdc.gov/nchs/data/hus/2011/094.pdf. Accessed March 14, 2013. 895. Hsia RY, Kellermann AL, Shen YC. Factors associated with clo- sures of emergency departments in the United States. JAMA. 2011;305:1978 1985. 896. Babcock Irvin C, Wyer PC, Gerson LW. Preventive care in the emer- gency department, part II: clinical preventive services: an emergency medicine evidence-based review: Society for Academic Emergency Medicine Public Health and Education Task Force Preventive Services Work Group. Acad Emerg Med. 2000;7:1042 1054. 897. Bernstein SL, Haukoos JS. Public health, prevention, and emergency medicine: a critical juxtaposition. Acad Emerg Med. 2008;15:190 193. 898. Reeves MJ, Hogan JG, Rafferty AP. Knowledge of stroke risk factors and warning signs among Michigan adults. Neurology. 2002;59:1547 1552. 899. Marsden C, Pinell MC, Joyce SM. Emergency physicians and preventive medicine. West J Med. 1988;149:345. 900. Delgado MK, Acosta CD, Ginde AA, Wang NE, Strehlow MC, Khandwala YS, Camargo CA Jr. National survey of preventive health services in US emergency departments. Ann Emerg Med. 2011;57:104 108.e2. 901. Karras DJ, Kruus LK, Cienki JJ, Wald MM, Ufberg JW, Shayne P, Wald DA, Heilpern KL. Utility of routine testing for patients with asymptom- atic severe blood pressure elevation in the emergency department. Ann Emerg Med. 2008;51:231 239. 902. Levy P, Ye H, Compton S, Zalenski R, Byrnes T, Flack JM, Welch R. Subclinical hypertensive heart disease in black patients with elevated blood pressure in an inner-city emergency department. Ann Emerg Med. 2012;60:467 474.e1. 903. Lehrmann JF, Tanabe P, Baumann BM, Jones MK, Martinovich Z, Adams JG. Knowledge translation of the American College of Emergency Physicians clinical policy on hypertension. Acad Emerg Med. 2007;14:1090 1096. 904. Baumann BM, Cline DM, Pimenta E. Treatment of hypertension in the emergency department. J Am Soc Hypertens. 2011;5:366 377. 905. Ginde AA, Cagliero E, Nathan DM, Camargo CA Jr. Value of risk stratification to increase the predictive validity of HbA1c in screen- ing for undiagnosed diabetes in the US population. J Gen Intern Med. 2008;23:1346 1353. 906. Jelinek GA, Weiland TJ, Moore G, Tan G, Maslin M, Bowman K, Ward G, O Dea K. Screening for type 2 diabetes with random finger-prick glu- cose and bedside HbA1c in an Australian emergency department. Emerg Med Australas. 2010;22:427 434. 907. George PM, Valabhji J, Dawood M, Henry JA. Screening for type 2 diabetes in the accident and emergency department. Diabet Med. 2005;22:1766 1769. 908. Ginde AA, Delaney KE, Pallin DJ, Camargo CA Jr. Multicenter survey of emergency physician management and referral for hyperglycemia. J Emerg Med. 2010;38:264 270. 909. Centers for Disease Control and Prevention (CDC). Annual smok- ing-attributable mortality, years of potential life lost, and economic costs United States, 1995 1999. MMWR Morb Mortal Wkly Rep. 2002;51:300 303. 910. Bernstein SL, Boudreaux ED, Cydulka RK, Rhodes KV, Lettman NA, Almeida SL, McCullough LB, Mizouni S, Kellermann AL; American College of Emergency Physicians Task Force on Smoking Cessation. Tobacco control interventions in the emergency department: a joint statement of emergency medicine organizations. Ann Emerg Med. 2006;48:e417-e426. 911. Katz DA, Vander Weg MW, Holman J, Nugent A, Baker L, Johnson S, Hillis SL, Titler M. The Emergency Department Action in Smoking Cessation (EDASC) trial: impact on delivery of smoking cessation coun- seling. Acad Emerg Med. 2012;19:409 420. 912. Bernstein SL, Bijur P, Cooperman N, Jearld S, Arnsten JH, Moadel A, Gallagher EJ. A randomized trial of a multicomponent cessation strategy for emergency department smokers. Acad Emerg Med. 2011;18:575 583. 913. Matchar DB, McCrory DC, Barnett HJ, Feussner JR. Medical treatment for stroke prevention. Ann Intern Med. 1994;121:41 53. 914. McDonald AJ, Pelletier AJ, Ellinor PT, Camargo CA Jr. Increasing US emergency department visit rates and subsequent hospital admissions for atrial fibrillation from 1993 to 2004. Ann Emerg Med. 2008;51:58 65. 915. Scott PA, PancioliAM, Davis LA, Frederiksen SM, Eckman J. Prevalence of atrial fibrillation and antithrombotic prophylaxis in emergency depart- ment patients. Stroke. 2002;33:2664 2669. 916. Kelly AM, Kerr D, Hew R. Prevention of stroke in chronic and recurrent atrial fibrillation: role of the emergency department in identification of at-risk patients. Aust Health Rev. 2001;24:61 65. 917. Meeker E, Dennehy CE, Weber EJ, Kayser SR. Emergency depart- ment management of patients on warfarin therapy. Ann Emerg Med. 2011;58:192 199. 918. D Onofrio G, Degutis LC. Preventive care in the emergency department: screening and brief intervention for alcohol problems in the emergency department: a systematic review. Acad Emerg Med. 2002;9:627 638. 919. Jones LA. Systematic review of alcohol screening tools for use in the emergency department. Emerg Med J. 2011;28:182 191. 920. Wang TC, Kyriacou DN, Wolf MS. Effects of an intervention brochure on emergency department patients safe alcohol use and knowledge. J Emerg Med. 2010;39:561 568. 921. Academic ED SBIRT Research Collaborative. The impact of screening, brief intervention, and referral for treatment on emergency department patients alcohol use. Ann Emerg Med. 2007;50:699 710, 710.e1-710.e6. 922. Bernstein E, Bernstein J, Feldman J, Fernandez W, Hagan M, Mitchell P, Safi C, Woolard R, Mello M, Baird J, Lee C, Bazargan-Hejazi S, Broderick K, Laperrier KA, Kellermann A, Wald MM, Taylor RE, Walton K, Grant-Ervin M, Rollinson D, Edwards D, Chan T, Davis D, Buchanan Marshall J, Aseltine R, James A, Schilling E, Abu-Hasaballah K, Baumann BM, Boudreaux ED, Maio RF, Cunningham RM, Murrell T, Doezema D, Anglin D, Eliassen A, Martin M, Pines J, Buchanan L, Turner J, D Onofrio G, Degutis LC, Owens P. An evidence based alco- hol screening, brief intervention and referral to treatment (SBIRT) cur- riculum for emergency department (ED) providers improves skills and utilization. Subst Abus. 2007;28:79 92. 923. Vaughn LM, Nabors L, Pelley TJ, Hampton RR, Jacquez F, Mahabee- Gittens EM. Obesity screening in the pediatric emergency department. Pediatr Emerg Care. 2012;28:548 552. 924. Williams JM, Chinnis AC, Gutman D. Health promotion practices of emergency physicians. Am J Emerg Med. 2000;18:17 21. 925. Yvonne Chan YF, Nagurka R, Richardson LD, Zaets SB, Brimacombe MB, Levine SR. Effectiveness of stroke education in the emergency department waiting room. J Stroke Cerebrovasc Dis. 2010;19:209 215. 926. Bensberg M, Kennedy M. A framework for health promoting emergency departments. Health Promot Int. 2002;17:179 188. 927. Li C, Balluz LS, Okoro CA, Strine TW, Lin JM, Town M, Garvin W, Murphy W, Bartoli W, Valluru B; Centers for Disease Control and Prevention (CDC). Surveillance of certain health behaviors and con- ditions among states and selected local areas: Behavioral Risk Factor Surveillance System, United States, 2009. MMWR Surveill Summ. 2011;60:1 250. 928. Li C, Balluz LS, Ford ES, Okoro CA, Zhao G, Pierannunzi C. A com- parison of prevalence estimates for selected health indicators and chronic diseases or conditions from the Behavioral Risk Factor Surveillance System, the National Health Interview Survey, and the National Health and Nutrition Examination Survey, 2007 2008. Prev Med. 2012;54:381 387. 929. Fang J, Yang Q, Hong Y, Loustalot F. Status of cardiovascular health among adult Americans in the 50 States and the District of Columbia, 2009. J Am Heart Assoc. 2012;1:e005371. 930. Holloway RG, Benesch C, Rush SR. Stroke prevention: narrowing the evidence-practice gap. Neurology. 2000;54:1899 1906. 931. Davis DA, Thomson MA, Oxman AD, Haynes RB. Changing physician performance: a systematic review of the effect of continuing medical education strategies. JAMA. 1995;274:700 705. 932. O Brien MA, Rogers S, Jamtvedt G, Oxman AD, Odgaard-Jensen J, Kristoffersen DT, Forsetlund L, Bainbridge D, Freemantle N, Davis DA, Haynes RB, Harvey EL. Educational outreach visits: effects on profes- sional practice and health care outcomes. Cochrane Database Syst Rev. 2007:CD000409. 933. Cohen SJ, Halvorson HW, Gosselink CA. Changing physician behavior to improve disease prevention. Prev Med. 1994;23:284 291. 934. Backer EL, Geske JA, McIlvain HE, Dodendorf DM, Minier WC. Improving female preventive health care delivery through prac- tice change: an Every Woman Matters study. J Am Board Fam Pract. 2005;18:401 408. 935. Fine LJ, Cutler JA. Hypertension and the treating physician: understand- ing and reducing therapeutic inertia. Hypertension. 2006;47:319 320. 936. Wright J, Bibby J, Eastham J, Harrison S, McGeorge M, Patterson C, Price N, Russell D, Russell I, Small N, Walsh M, Young J. Multifaceted implementation of stroke prevention guidelines in primary care: cluster- randomised evaluation of clinical and cost effectiveness. Qual Saf Health Care. 2007;16:51 59. 937. Anderson RT, Camacho F, Iaconi AI, Tegeler CH, Balkrishnan R. Enhancing the effectiveness of community stroke risk screening: a ran- domized controlled trial. J Stroke Cerebrovasc Dis. 2011;20:330 335. 938. Shannon KC, Sinacore JM, Bennett SG, Joshi AM, Sherin KM, Deitrich A. Improving delivery of preventive health care with the Comprehensive Annotated Reminder Tool (CART). J Fam Pract. 2001;50:767 771. 939. Choma NN, Huang RL, Dittus RS, Burnham KE, Roumie CL. Quality improvement initiatives improve hypertension care among veterans. Circ Cardiovasc Qual Outcomes. 2009;2:392 398. 940. Shea S, DuMouchel W, Bahamonde L. A meta-analysis of 16 random- ized controlled trials to evaluate computer-based clinical reminder sys- tems for preventive care in the ambulatory setting. J Am Med Inform Assoc. 1996;3:399 409. 941. Baskerville NB, Hogg W, Lemelin J. Process evaluation of a tailored multifaceted approach to changing family physician practice patterns improving preventive care. J Fam Pract. 2001;50:W242 W249. 942. Frijling B, Hulscher ME, van Leest LA, Braspenning JC, van den Hoogen H, Drenthen AJ, Grol RP. Multifaceted support to improve preventive cardiovascular care: a nationwide, controlled trial in general practice. Br J Gen Pract. 2003;53:934 941. 943. Stone EG, Morton SC, Hulscher ME, Maglione MA, Roth EA, Grimshaw JM, Mittman BS, Rubenstein LV, Rubenstein LZ, Shekelle PG. Interventions that increase use of adult immunization and cancer screening services: a meta-analysis. Ann Intern Med. 2002;136:641 651. 944. Chaudhry B, Wang J, Wu S, Maglione M, Mojica W, Roth E, Morton SC, Shekelle PG. Systematic review: impact of health information technol- ogy on quality, efficiency, and costs of medical care. Ann Intern Med. 2006;144:742 752. 945. de Koning JS, Klazinga N, Koudstaal PJ, Prins AD, Borsboom GJ, Mackenbach JP. Quality of stroke prevention in general practice: relationship with practice organization. Int J Qual Health Care. 2005;17:59 65. 946. Houle SK, Chuck AW, McAlister FA, Tsuyuki RT. Effect of a phar- macist-managed hypertension program on health system costs: an evaluation of the Study of Cardiovascular Risk Intervention by Pharmacists-Hypertension (SCRIP-HTN). Pharmacotherapy. 2012;32:527 537. 947. Heisler M, Hofer TP, Schmittdiel JA, Selby JV, Klamerus ML, Bosworth HB, Bermann M, Kerr EA. Improving blood pressure control through a clinical pharmacist outreach program in patients with diabetes mellitus in 2 high-performing health systems: the adherence and intensification of medications cluster randomized, controlled pragmatic trial. Circulation. 2012;125:2863 2872. 948. Harris MF, Fanaian M, Jayasinghe UW, Passey ME, McKenzie SH, Powell Davies G, Lyle DM, Laws RA, Schutze H, Wan Q. A cluster ran- domised controlled trial of vascular risk factor management in general practice. Med J Aust. 2012;197:387 393. 949. Tricco AC, Ivers NM, Grimshaw JM, Moher D, Turner L, Galipeau J, Halperin I, Vachon B, Ramsay T, Manns B, Tonelli M, Shojania K. Effectiveness of quality improvement strategies on the manage- ment of diabetes: a systematic review and meta-analysis. Lancet. 2012;379:2252 2261. 950. Bosworth HB, Olsen MK, Grubber JM, Neary AM, Orr MM, Powers BJ, Adams MB, Svetkey LP, Reed SD, Li Y, Dolor RJ, Oddone EZ. Two self-management interventions to improve hypertension control: a ran- domized trial. Ann Intern Med. 2009;151:687 695. 951. Bosworth HB, Powers BJ, Olsen MK, McCant F, Grubber J, Smith V, Gentry PW, Rose C, Van Houtven C, Wang V, Goldstein MK, Oddone EZ. Home blood pressure management and improved blood pressure control: results from a randomized controlled trial. Arch Intern Med. 2011;171:1173 1180. 952. Asch SM, McGlynn EA, Hogan MM, Hayward RA, Shekelle P, Rubenstein L, Keesey J, Adams J, Kerr EA. Comparison of quality of care for patients in the Veterans Health Administration and patients in a national sample. Ann Intern Med. 2004;141:938 945. 953. Schilling L, Chase A, Kehrli S, Liu AY, Stiefel M, Brentari R. Kaiser Permanente s performance improvement system, part 1: from bench- marking to executing on strategic priorities. Jt Comm J Qual Patient Saf. 2010;36:484 498. 954. Kupersmith J, Francis J, Kerr E, Krein S, Pogach L, Kolodner RM, Perlin JB. Advancing evidence-based care for diabetes: lessons from the Veterans Health Administration. Health Aff (Millwood). 2007;26:w156 w168. 955. Cadilhac DA, Carter R, Thrift AG, Dewey HM. Organized blood pres- sure control programs to prevent stroke in Australia: would they be cost- effective? Stroke. 2012;43:1370 1375.