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Overview of secondary prevention of ischemic stroke

Karen L Furie, MD, MPH
Natalia S Rost, MD, MPH
Section Editor
Scott E Kasner, MD
Deputy Editor
John F Dashe, MD, PhD


The management of treatable risk factors and common mechanisms of brain ischemia is important for reducing the risk of ischemic stroke. This topic will review the risk factors for stroke, with a focus on secondary prevention in patients who have a history of transient ischemic attack or ischemic stroke, or are considered to have a high risk of ischemic stroke due to the presence of coronary heart disease or diabetes.

Risk factors for hemorrhagic stroke are reviewed elsewhere. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Risk factors' and "Aneurysmal subarachnoid hemorrhage: Epidemiology, risk factors, and pathogenesis", section on 'Risk factors'.)

The role of primary prevention for cardiovascular disease, including stroke, is discussed separately. (See "Overview of primary prevention of coronary heart disease and stroke".)


The major modifiable risk factors for stroke are the following [1-4]:


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Literature review current through: Nov 2017. | This topic last updated: Nov 22, 2017.
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  1. Harmsen P, Lappas G, Rosengren A, Wilhelmsen L. Long-term risk factors for stroke: twenty-eight years of follow-up of 7457 middle-aged men in Göteborg, Sweden. Stroke 2006; 37:1663.
  2. Hankey GJ. Potential new risk factors for ischemic stroke: what is their potential? Stroke 2006; 37:2181.
  3. Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin 2008; 26:871.
  4. O'Donnell MJ, Chin SL, Rangarajan S, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet 2016; 388:761.
  5. Jerrard-Dunne P, Cloud G, Hassan A, Markus HS. Evaluating the genetic component of ischemic stroke subtypes: a family history study. Stroke 2003; 34:1364.
  6. Jood K, Ladenvall C, Rosengren A, et al. Family history in ischemic stroke before 70 years of age: the Sahlgrenska Academy Study on Ischemic Stroke. Stroke 2005; 36:1383.
  7. Meschia JF, Worrall BB, Rich SS. Genetic susceptibility to ischemic stroke. Nat Rev Neurol 2011; 7:369.
  8. Howard VJ. Reasons underlying racial differences in stroke incidence and mortality. Stroke 2013; 44:S126.
  9. Persky RW, Turtzo LC, McCullough LD. Stroke in women: disparities and outcomes. Curr Cardiol Rep 2010; 12:6.
  10. Bushnell C, McCullough LD, Awad IA, et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:1545.
  11. Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke 1991; 22:312.
  12. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903.
  13. Rapsomaniki E, Timmis A, George J, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people. Lancet 2014; 383:1899.
  14. Vermeer SE, Longstreth WT Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol 2007; 6:611.
  15. Prabhakaran S, Wright CB, Yoshita M, et al. Prevalence and determinants of subclinical brain infarction: the Northern Manhattan Study. Neurology 2008; 70:425.
  16. Das RR, Seshadri S, Beiser AS, et al. Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study. Stroke 2008; 39:2929.
  17. Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet 2010; 375:895.
  18. Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet 2010; 375:938.
  19. Ockene IS, Miller NH. Cigarette smoking, cardiovascular disease, and stroke: a statement for healthcare professionals from the American Heart Association. American Heart Association Task Force on Risk Reduction. Circulation 1997; 96:3243.
  20. Kawachi I, Colditz GA, Stampfer MJ, et al. Smoking cessation and decreased risk of stroke in women. JAMA 1993; 269:232.
  21. Kurth T, Kase CS, Berger K, et al. Smoking and risk of hemorrhagic stroke in women. Stroke 2003; 34:2792.
  22. Wilson PW, Hoeg JM, D'Agostino RB, et al. Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis. N Engl J Med 1997; 337:516.
  23. Li C, Engström G, Hedblad B, et al. Risk factors for stroke in subjects with normal blood pressure: a prospective cohort study. Stroke 2005; 36:234.
  24. Wolf PA, D'Agostino RB, Kannel WB, et al. Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA 1988; 259:1025.
  25. Peters SA, Huxley RR, Woodward M. Smoking as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke 2013; 44:2821.
  26. Wannamethee SG, Shaper AG, Whincup PH, Walker M. Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995; 274:155.
  27. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:2160.
  28. Arvanitakis Z, Schneider JA, Wilson RS, et al. Diabetes is related to cerebral infarction but not to AD pathology in older persons. Neurology 2006; 67:1960.
  29. Janghorbani M, Hu FB, Willett WC, et al. Prospective study of type 1 and type 2 diabetes and risk of stroke subtypes: the Nurses' Health Study. Diabetes Care 2007; 30:1730.
  30. Emerging Risk Factors Collaboration, Sarwar N, Gao P, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375:2215.
  31. Luitse MJ, Biessels GJ, Rutten GE, Kappelle LJ. Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol 2012; 11:261.
  32. Peters SA, Huxley RR, Woodward M. Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes. Lancet 2014; 383:1973.
  33. Vermeer SE, Sandee W, Algra A, et al. Impaired glucose tolerance increases stroke risk in nondiabetic patients with transient ischemic attack or minor ischemic stroke. Stroke 2006; 37:1413.
  34. Vitelli LL, Shahar E, Heiss G, et al. Glycosylated hemoglobin level and carotid intimal-medial thickening in nondiabetic individuals. The Atherosclerosis Risk in Communities Study. Diabetes Care 1997; 20:1454.
  35. Jørgensen L, Jenssen T, Joakimsen O, et al. Glycated hemoglobin level is strongly related to the prevalence of carotid artery plaques with high echogenicity in nondiabetic individuals: the Tromsø study. Circulation 2004; 110:466.
  36. Yaghi S, Elkind MS. Lipids and Cerebrovascular Disease: Research and Practice. Stroke 2015; 46:3322.
  37. Amarenco P. Lipid lowering and recurrent stroke: another stroke paradox? Eur Heart J 2005; 26:1818.
  38. Leppälä JM, Virtamo J, Fogelholm R, et al. Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants. Stroke 1999; 30:2535.
  39. Zhang X, Patel A, Horibe H, et al. Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. Int J Epidemiol 2003; 32:563.
  40. Kurth T, Everett BM, Buring JE, et al. Lipid levels and the risk of ischemic stroke in women. Neurology 2007; 68:556.
  41. Horenstein RB, Smith DE, Mosca L. Cholesterol predicts stroke mortality in the Women's Pooling Project. Stroke 2002; 33:1863.
  42. Shahar E, Chambless LE, Rosamond WD, et al. Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2003; 34:623.
  43. Bots ML, Elwood PC, Nikitin Y, et al. Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe. J Epidemiol Community Health 2002; 56 Suppl 1:i19.
  44. Tirschwell DL, Smith NL, Heckbert SR, et al. Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups. Neurology 2004; 63:1868.
  45. Corvol JC, Bouzamondo A, Sirol M, et al. Differential effects of lipid-lowering therapies on stroke prevention: a meta-analysis of randomized trials. Arch Intern Med 2003; 163:669.
  46. Lindenstrøm E, Boysen G, Nyboe J. Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study. BMJ 1994; 309:11.
  47. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008; 300:2142.
  48. Bansal S, Buring JE, Rifai N, et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 2007; 298:309.
  49. Håheim LL, Holme I, Hjermann I, Leren P. Risk factors of stroke incidence and mortality. A 12-year follow-up of the Oslo Study. Stroke 1993; 24:1484.
  50. Bowman TS, Sesso HD, Ma J, et al. Cholesterol and the risk of ischemic stroke. Stroke 2003; 34:2930.
  51. Chomistek AK, Manson JE, Stefanick ML, et al. Relationship of sedentary behavior and physical activity to incident cardiovascular disease: results from the Women's Health Initiative. J Am Coll Cardiol 2013; 61:2346.
  52. Gillum RF, Mussolino ME, Ingram DD. Physical activity and stroke incidence in women and men. The NHANES I Epidemiologic Follow-up Study. Am J Epidemiol 1996; 143:860.
  53. Billinger SA, Arena R, Bernhardt J, et al. Physical activity and exercise recommendations for stroke survivors: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:2532.
  54. Bang OY, Ovbiagele B, Kim JS. Nontraditional Risk Factors for Ischemic Stroke: An Update. Stroke 2015; 46:3571.
  55. Mauriello A, Sangiorgi G, Palmieri G, et al. Hyperfibrinogenemia is associated with specific histocytological composition and complications of atherosclerotic carotid plaques in patients affected by transient ischemic attacks. Circulation 2000; 101:744.
  56. Sabeti S, Exner M, Mlekusch W, et al. Prognostic impact of fibrinogen in carotid atherosclerosis: nonspecific indicator of inflammation or independent predictor of disease progression? Stroke 2005; 36:1400.
  57. Eikelboom JW, Hankey GJ, Anand SS, et al. Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000; 31:1069.
  58. Iso H, Moriyama Y, Sato S, et al. Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese. Circulation 2004; 109:2766.
  59. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375:132.
  60. Di Napoli M, Schwaninger M, Cappelli R, et al. Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members. Stroke 2005; 36:1316.
  61. Grau AJ, Boddy AW, Dukovic DA, et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004; 35:1147.
  62. Elkind MS, Sciacca RR, Boden-Albala B, et al. Relative elevation in baseline leukocyte count predicts first cerebral infarction. Neurology 2005; 64:2121.
  63. Gorelick PB. Lipoprotein-associated phospholipase A2 and risk of stroke. Am J Cardiol 2008; 101:34F.
  64. Nambi V, Hoogeveen RC, Chambless L, et al. 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.
  65. Katan M, Moon YP, Paik MC, et al. Lipoprotein-associated phospholipase A2 is associated with atherosclerotic stroke risk: the Northern Manhattan Study. PLoS One 2014; 9:e83393.
  66. Koren-Morag N, Goldbourt U, Tanne D. Relation between the metabolic syndrome and ischemic stroke or transient ischemic attack: a prospective cohort study in patients with atherosclerotic cardiovascular disease. Stroke 2005; 36:1366.
  67. Kurl S, Laukkanen JA, Niskanen L, et al. Metabolic syndrome and the risk of stroke in middle-aged men. Stroke 2006; 37:806.
  68. Chen HJ, Bai CH, Yeh WT, et al. Influence of metabolic syndrome and general obesity on the risk of ischemic stroke. Stroke 2006; 37:1060.
  69. Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome vs Framingham Risk Score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch Intern Med 2005; 165:2644.
  70. Ninomiya T, Kubo M, Doi Y, et al. Impact of metabolic syndrome on the development of cardiovascular disease in a general Japanese population: the Hisayama study. Stroke 2007; 38:2063.
  71. Boden-Albala B, Sacco RL, Lee HS, et al. Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study. Stroke 2008; 39:30.
  72. Wang J, Ruotsalainen S, Moilanen L, et al. The metabolic syndrome predicts incident stroke: a 14-year follow-up study in elderly people in Finland. Stroke 2008; 39:1078.
  73. Rodriguez-Colon SM, Mo J, Duan Y, et al. Metabolic syndrome clusters and the risk of incident stroke: the atherosclerosis risk in communities (ARIC) study. Stroke 2009; 40:200.
  74. Hanchaiphiboolkul S, Suwanwela NC, Poungvarin N, et al. Risk of metabolic syndrome for stroke is not greater than the sum of its components: Thai Epidemiologic Stroke (TES) study. J Stroke Cerebrovasc Dis 2013; 22:e264.
  75. Morris B, Partap S, Yeom K, et al. Cerebrovascular disease in childhood cancer survivors: A Children's Oncology Group Report. Neurology 2009; 73:1906.
  76. Lam WW, Leung SF, So NM, et al. Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer 2001; 92:2357.
  77. Plummer C, Henderson RD, O'Sullivan JD, Read SJ. Ischemic stroke and transient ischemic attack after head and neck radiotherapy: a review. Stroke 2011; 42:2410.
  78. Kasner SE. Treatment of "other" causes of stroke. In: Stroke: Pathophsyiology, Diagnosis, and Management, 4th ed, Mohr JP, Choi DW, Grotta JC, et al (Eds), Churchill Livingstone, Philadelphia 2004. p.1059.
  79. Hackam DG, Spence JD. Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study. Stroke 2007; 38:1881.
  80. De Schryver EL, Algra A, Kappelle LJ, et al. Vitamin K antagonists versus antiplatelet therapy after transient ischaemic attack or minor ischaemic stroke of presumed arterial origin. Cochrane Database Syst Rev 2012; :CD001342.
  81. Bucher HC, Griffith LE, Guyatt GH. Effect of HMGcoA reductase inhibitors on stroke. A meta-analysis of randomized, controlled trials. Ann Intern Med 1998; 128:89.
  82. Donnan GA, Davis SM. Stroke and cholesterol: weakness of risk versus strength of therapy. Stroke 2004; 35:1526.
  83. Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998; 279:1643.
  84. Amarenco P, Labreuche J, Lavallée P, Touboul PJ. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 2004; 35:2902.
  85. Hegland O, Dickstein K, Larsen JP. Effect of simvastatin in preventing progression of carotid artery stenosis. Am J Cardiol 2001; 87:643.
  86. de Sauvage Nolting PR, de Groot E, Zwinderman AH, et al. Regression of carotid and femoral artery intima-media thickness in familial hypercholesterolemia: treatment with simvastatin. Arch Intern Med 2003; 163:1837.
  87. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129:S1.
  88. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009; 8:453.
  89. Naci H, Brugts JJ, Fleurence R, Ades AE. Comparative effects of statins on major cerebrovascular events: a multiple-treatments meta-analysis of placebo-controlled and active-comparator trials. QJM 2013; 106:299.
  90. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355:549.
  91. 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.
  92. Plehn JF, Davis BR, Sacks FM, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators. Circulation 1999; 99:216.
  93. Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361:1149.
  94. Fonville S, Zandbergen AA, Koudstaal PJ, den Hertog HM. Prediabetes in patients with stroke or transient ischemic attack: prevalence, risk and clinical management. Cerebrovasc Dis 2014; 37:393.
  95. Kernan WN, Inzucchi SE, Viscoli CM, et al. Impaired insulin sensitivity among nondiabetic patients with a recent TIA or ischemic stroke. Neurology 2003; 60:1447.
  96. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med 2016; 374:1321.
  97. Zhang Y, Tuomilehto J, Jousilahti P, et al. Lifestyle factors on the risks of ischemic and hemorrhagic stroke. Arch Intern Med 2011; 171:1811.
  98. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129:S76.