pressure: a prospective cohort study. Stroke 2005; 36:234. 60. Wolf PA, D'Agostino RB, Kannel WB, et al. Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA 1988; 259:1025. 61. 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. 62. Wannamethee SG, Shaper AG, Whincup PH, Walker M. Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995; 274:155. 63. 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. 64. 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. 65. 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. 66. English C, MacDonald-Wicks L, Patterson A, et al. The role of diet in secondary stroke prevention. Lancet Neurol 2021; 20:150. 67. 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. 68. Indave BI, Sordo L, Bravo MJ, et al. Risk of stroke in prescription and other amphetamine- type stimulants use: A systematic review. Drug Alcohol Rev 2018; 37:56. 69. Sordo L, Indave BI, Barrio G, et al. Cocaine use and risk of stroke: a systematic review. Drug Alcohol Depend 2014; 142:1. 70. Guo Y, Yue XJ, Li HH, et al. Overweight and Obesity in Young Adulthood and the Risk of Stroke: a Meta-analysis. J Stroke Cerebrovasc Dis 2016; 25:2995. 71. Bang OY, Ovbiagele B, Kim JS. Nontraditional Risk Factors for Ischemic Stroke: An Update. Stroke 2015; 46:3571. 72. 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 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 24/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate ischemic stroke. Stroke 2000; 31:1069. 73. 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. 74. Morris B, Partap S, Yeom K, et al. Cerebrovascular disease in childhood cancer survivors: A Children's Oncology Group Report. Neurology 2009; 73:1906. 75. Lam WW, Leung SF, So NM, et al. Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer 2001; 92:2357. 76. 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. 77. Kasner SE. Treatment of "other" causes of stroke. In: Stroke: Pathophsyiology, Diagnosis, an d Management, 4th ed, Mohr JP, Choi DW, Grotta JC, et al (Eds), Churchill Livingstone, Philad elphia 2004. p.1059. Topic 1120 Version 65.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 25/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate GRAPHICS Known cardiovascular disease and similar risk Patients with the following are at high risk for a second (or first) cardiovascular disease event: Coronary heart disease Myocardial infarction Angina Coronary revascularization Cerebrovascular disease Stroke Transient ischemic attack Peripheral arterial disease Multiple risk factors that confer a 10-year risk of CVD >20% 2 Chronic kidney disease with estimated GFR <45 mL/min per 1.73 m * CVD: cardiovascular disease; GFR: glomerular filtration rate. Statin doses may require adjustment in patients with chronic kidney disease. Graphic 91576 Version 3.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 26/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Antithrombotic therapy according to cause of acute ischemic stroke This algorithm is intended to provide basic guidance regarding the immediate use of antithrombotic therapy with an acute ischemic stroke. For further details, including scoring of the NIHSS and suggested dosing regim antithrombotic agents, refer to the relevant UpToDate topic reviews. https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 27/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate HTN: hypertension; SBP: systolic blood pressure; DBP: diastolic blood pressure; ICA: internal carotid artery; C endarterectomy; OA: oral anticoagulation; CAS: carotid artery stenting; DAPT: dual antiplatelet therapy (eg, a clopidogrel, or aspirin and ticagrelor); NIHSS: National Institutes of Health Stroke Scale; CT: computed tomog magnetic resonance imaging. Brain and neurovascular imaging, cardiac evaluation, and (for select patients) other laboratory tests. Indications for long-term oral anticoagulation include atrial fibrillation, ventricular thrombus, mechanical h treatment of venous thromboembolism. "Large" infarcts are defined as those that involve more than one-third of the middle cerebral artery territor one-half of the posterior cerebral artery territory based upon neuroimaging with CT or MRI. Though less relia infarct size can also be defined clinically (eg, NIHSS score >15). Long-term aspirin therapy is alternative (though less effective) if OA contraindicated or refused. Direct oral anticoagulant agents have a more rapid anticoagulant effect than warfarin, a factor that may inf choice of agent and timing of OA initiation. Some experts prefer DAPT, based upon observational evidence. Long-term single-agent antiplatelet therapy for secondary stroke prevention with aspirin, clopidogrel, or as release dipyridamole. Graphic 131701 Version 2.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 28/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Immediate antithrombotic treatment of transient ischemic attack (TIA) This algorithm is intended to provide basic guidance regarding the use of immediate use of antithrombotic therapy for patients with a TIA. For further details, including suggested dosing regimens of antiplatelet and anticoagulant agents, refer to the relevant UpToDate topic reviews. 2 ABCD : age, blood pressure, clinical features, duration of symptoms, and diabetes; DAPT: dual antiplatelet therapy (eg, aspirin and clopidogrel, or aspirin and ticagrelor); BP: blood pressure; SBP: systolic blood pressure; DBP: diastolic blood pressure. Indications for long-term oral anticoagulation include embolism prevention for patients with atrial fibrillation, ventricular thrombus, mechanical heart valve, and treatment of venous thromboembolism. Graphic 131692 Version 1.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 29/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Immediate antithrombotic treatment of acute ischemic stroke This algorithm is intended to provide basic guidance regarding the immediated use of antithrombotic therapy for patients with an acute ischemic stroke. For further details, including scoring of the NIHSS and suggested dosing regimens of antithrombotic agents, refer to the relevant UpToDate topic reviews. OA: oral anticoagulants; IVT: intravenous thrombolysis; MT: mechanical thrombectomy; NIHSS: National Institutes of Health Stroke Scale; DAPT: dual antiplatelet therapy (eg, aspirin and clopidogrel, or aspirin and ticagrelor). Refer to text and associated algorithm for details. Brain and large vessel imaging, cardiac evaluation, and (for select patients) other laboratory tests. https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 30/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate For severe systemic or symptomatic intracranial bleeding, withhold all anticoagulant and antiplatelet therapy for one to two weeks or until the patient is stable. Graphic 131697 Version 2.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 31/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Stroke mortality related to blood pressure and age Stroke mortality rate, pictured on a log scale with 95% CI, in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the start of that decade. Stroke mortality increases with both higher pressures and older ages. For diastolic pressure, each age-specific regression line ignores the left-hand point (ie, at slightly less than 75 mmHg) for which the risk lies significantly above the fitted regression line (as indicated by the broken line below 75 mmHg). CI: confidence interval. Data from Prospective Studies Collaboration, Lancet 2002; 360:1903. Graphic 66793 Version 5.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 32/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Coronary heart disease mortality related to blood pressure and age Coronary heart disease (CHD) mortality rate, pictured on a log scale with 95% confidence intervals (CI), in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the start of that decade. CHD mortality increases with both higher pressures and older ages. For diastolic pressure, each age- specific regression line ignores the left-hand point (ie, at slightly less than 75 mmHg) for which the risk lies significantly above the fitted regression line (as indicated by the broken line below 75 mmHg). IHD: ischemic heart disease. Reproduced from: Lewington S, Clarke R, Qizilbash N, et al. Age-speci c 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. Illustration used with the permission of Elsevier. All rights reserved. Graphic 75106 Version 9.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 33/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Goal blood pressure according to baseline risk for cardiovascular disease and method of measuring blood pressure Routine/conventional office blood pressure Unattended AOBPM, (manual measurement daytime ABPM, or home with stethoscope or blood pressure oscillometric device)* Higher-risk population 125 to 130/<80 120 to 125/<80 Known ASCVD Heart failure Diabetes mellitus Chronic kidney disease Age 65 years Calculated 10-year risk of ASCVD event 10% Lower-risk 130 to 139/<90 125 to 135/<90 None of the above risk factors All target ranges presented above are in mmHg. On average, blood pressure readings are 5 to 10 mmHg lower with digital, unattended, or out-of- office methods of measurement (ie, AOBPM, daytime ABPM, home blood pressure) than with routine/standard methods of office measurement (ie, manual auscultatory or oscillometric measurement), presumably due to the "white coat effect." However, it is critical to realize that this average difference in blood pressures according to the methodology of measurement applies to the population and not the individual. Some patients do not experience a white coat effect, and, therefore, there is some uncertainty in setting goals that are specific to the method of measurement. When treating to these goals, a patient may (inadvertently) attain a blood pressure below the given target. Provided the patient does not develop symptoms, side effects, or adverse events as a result of the treatment regimen, then reducing or withdrawing antihypertensive medications is unnecessary. Less aggressive goals than those presented in the table may be appropriate for specific groups of patients, including those with postural hypotension, the frail older adult patient, and those with side effects to multiple antihypertensive medications. AOBPM: automated oscillometric blood pressure monitoring; ABPM: ambulatory blood pressure monitoring; ASCVD: atherosclerotic cardiovascular disease; ACC/AHA: American College of Cardiology/American Heart Association. https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 34/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Office blood pressure must be performed adequately in order to use such measurements to manage patients. Critical to an adequate office assessment of blood pressure are proper patient positioning (eg, seated in a chair, feet flat on the floor, arm supported, remove clothing covering the location of cuff placement) and proper technique (eg, calibrated device, proper-sized cuff). The average of multiple measurements should be used for management. Refer to UpToDate topics on measurement of blood pressure. Office readings should not be used to manage blood pressure unless it is performed adequately. Home blood pressure, like office blood pressure, must be performed adequately in order for the measurements to be used to manage patients. First, the accuracy of the home blood pressure device must be verified in the clinician's office. Second, the clinician should verify that the cuff and bladder that the patient will use are the appropriate size. Third, patients should measure their pressure after several minutes of rest and while seated in a chair (back supported and feet flat on the floor) with their arm supported (eg, resting on a table). Fourth, the blood pressure should be measured at different times per day and over multiple days. The average value of these multiple measurements is used for management. Home blood pressure readings should not be used to manage blood pressure unless it is performed adequately and in conjunction with office blood pressure or ambulatory blood pressure. The level of evidence supporting the lower goal in higher-risk individuals is stronger for some risk groups (eg, patients with known coronary heart disease, patients with a calculated 10-year risk 15%, chronic kidney disease) than for other risk groups (eg, patients with diabetes, patients with a prior stroke). Refer to UpToDate topics on goal blood pressure for a discussion of the evidence. Prior history of coronary heart disease (acute coronary syndrome or stable angina), prior stroke or transient ischemic attack, prior history of peripheral artery disease. In older adults with severe frailty, dementia, and/or a limited life expectancy, or in patients who are nonambulatory or institutionalized (eg, reside in a skilled nursing facility), we individualize goals and share decision-making with the patient, relatives, and caretakers, rather than targeting one of the blood pressure goals in the table. The 2013 ACC/AHA cardiovascular risk assessment calculator should be used to estimate 10-year cardiovascular disease risk. In the large subgroup of patients who have an initial (pretreatment) blood pressure 140/ 90 mmHg, but who do not have any of the other listed cardiovascular risk factors, some experts would set a more aggressive blood pressure goal of <130/<80 mmHg rather than those presented in the table. This more aggressive goal would likely reduce the chance of developing severe hypertension and ultimately lower the relative risk of cardiovascular events in these lower-risk patients over the long term. However, the absolute benefit of more aggressive blood pressure lowering in these patients is comparatively small, and a lower goal would require more intensive pharmacologic therapy and corresponding side effects. Graphic 117101 Version 3.0 https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 35/36 7/6/23, 12:51 PM Overview of secondary prevention of ischemic stroke - UpToDate Contributor Disclosures Natalia S Rost, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Alexis Simpkins, MD, PhD, MSCR, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke/print 36/36