Stroke and TIA: Epidemiology, Risk Factors, and the Need for Early Intervention

Supplements and Featured Publications, Secondary Prevention of Noncardioembolic Ischemic Stroke, Volume 14, Issue 7 Suppl

The risk of recurrent stroke in patients who have suffered a prior stroke or transient ischemic attack (TIA) is significant. It is imperative that individuals who report symptoms of a cerebrovascular event receive immediate medical attention— preferably at a hospital—to help determine its origin and impact. Many researchers recommend that any evaluation include neuroimaging studies to target those patients who would benefit most from secondary prevention, such as antithrombotic therapy.

This article defines the 2 main types of stroke and their respective subtypes and discusses the debate over how to define stroke versus TIA. Additionally, the article talks about the incidence of stroke, related morbidity and mortality rates, and several risk factors that predispose an individual to stroke and recurrent stroke. Several systems have been established to help determine the likelihood of stroke for patients with concurrent risk factors. Measures for secondary prevention can be initiated to address many of these risk factors.

The importance of early intervention cannot be underestimated. Rapid treatment following a stroke or TIA can minimize cerebrovascular damage and prevent recurrence; addressing modifiable risk factors can reduce the risk of subsequent cardiovascular and cerebrovascular events. Facilitating the initiation of effective secondary preventive therapy must become a priority in managed care.

(Am J Manag Care. 2008;14:S204-S211)

Every 40 to 45 seconds someone in the United States suffers a stroke.1,2 One quarter of initial stroke survivors suffer a second stroke within 5 years.2 Long before experiencing a stroke, many people have cerebrovascular risk factors that have not been adequately addressed, such as transient ischemic attacks (TIAs). TIAs are frequently followed by stroke.2,3 Sometimes TIAs remain unidentified because patients did not seek medical attention. TIAs may also be misdiagnosed or go untreated because baseline function returned prior to a medical evaluation.4 Any diagnosed stroke or TIA deserves rapid evaluation and long-term therapy to help prevent further cerebrovascular events.3

Defining Stroke and TIA

Stroke is a neurologic event related to diseases of the cerebral circulation. Symptoms of stroke include sudden severe headache, focal muscular weakness or numbness, impaired vision, dizziness, confusion, or difficulty speaking or understanding speech. Visual loss and weakness or numbness are frequently relegated to one side of the body.

TIAs are briefer episodes of neurologic deficit that occur as a result of focal cerebral or retinal ischemia.5,6 TIAs were once regarded as benign7 but are now recognized as warning signs of underlying cerebrovascular disease with the potential to cause permanent brain injury.3 Most TIAs resolve within 1 hour.3,6,7 Only 2% to 15% of TIAs that fail to resolve within 1 hour will do so within 24 hours.7

Strokes and TIAs previously were diagnosed on the basis of clinical impression alone, and traditional definitions held that TIA should be diagnosed when symptoms persisted for fewer than 24 hours, whereas a completed stroke should be diagnosed when symptoms persisted beyond 24 hours.3,6,7 It was also thought that TIAs left no permanent deficits.7,8

The advent of sophisticated neuroimaging technologies has blurred the line between stroke and TIA.7 Computed tomography (CT) studies from the 1980s to the 1990s found that 15% to 20% of TIA patients had cerebral infarction in areas relevant to symptoms.7 Recently, diffusion-weighted magnetic resonance imaging (DWI) has demonstrated lesions suggestive of permanent ischemic injury in some TIA patients.7 This has led some researchers to propose that the definition of TIA be modified to specify that the condition leaves no evidence of acute infarction on neuroimaging studies.3,5-7 According to this definition, imaging studies that show relevant infarction would indicate stroke, regardless of the duration of symptoms.7

Some researchers recommend that all TIA patients undergo brain imaging urgently—as soon as possible after the onset of symptoms—to identify causes and target secondary prevention efforts.7,9 CT scanning and DWI can demonstrate regions of injury and help to distinguish between hemorrhage, ischemic infarction, and other etiologies, such as tumor.3,5,7,10 DWI can also help differentiate an infarction from penumbra (the region surrounding the ischemic core that is hypoperfused but not yet infarcted).3 In patients who have experienced TIA or a mild-to-moderate ischemic stroke, imaging modalities such as ultrasonography, CT angiography, and magnetic resonance angiography can detect internal carotid artery stenosis,5,9 a condition that may benefit from early treatment with carotid endarterectomy.9

Based on the traditional definition of TIA, some clinicians might delay intervention for 24 hours after symptoms first appear to see whether they subside. Waiting could be problematic in cases where the cause of suspected TIA requires immediate treatment. Also, within this 24-hour window, the patient could experience a completed stroke following TIA.3,4,7 Hospital observation enables immediate intervention if the patient should experience a subsequent stroke.9 Damage in the penumbra of acute ischemic stroke may be reversible, and rapid treatment can prevent it from becoming incorporated into the infarct.10 Prompt thrombolysis can improve outcomes10,11 with an acceptable level of risk for intracranial hemorrhage (ICH), provided proper care is exercised in patient selection.10

TIAs require immediate evaluation, and treatment should be initiated promptly to prevent subsequent stroke.5 Most patients who report TIA-like symptoms should be sent to the emergency department.5 In patients who do not seek medical attention or who are not referred for imaging studies, TIAs serve as unheeded warnings of possible cerebrovascular disease.

Stroke Types and Subtypes

ICH—the presence of blood within the main cellular mass of the brain—accounts for ~10% of all strokes.1 The incidence of ICH due to the use of oral anticoagulants has increased as these therapies have become more prevalent.18,19 In elderly individuals, the deposition of amyloid protein into blood vessel walls may cause hemorrhage. In most cases of ICH, however, chronic hypertension leads to the degeneration of smaller brain arteries and microaneurysms; bleeding originates from tears at the bifurcation between the vessels. The patient’s symptoms may change in relation to additional bleeding and expansion of the affected area; note that rupture of a cerebral artery can cause immediate death.

Subarachnoid hemorrhage (SAH) is the second hemorrhagic subtype and accounts for 3% of all strokes.1 SAH is most prevalent among middle-aged women and has a high mortality rate.15 SAH usually results from the rupture of a cerebral aneurysm at a vessel bifurcation.20 Vasospasm of brain arteries is a common complication of SAH and can lead to a subsequent ischemic brain injury.20

Ischemic Subtypes

An estimated 780,000 strokes occur each year in the United States, of which 180,000 are recurrent.1 In adults ≥20 years old, the prevalence of stroke is ~2.3 million men and ~3.4 million women.1 The incidence of TIA is estimated at 200,000 to 500,000 per year.5 However, 15% of stroke patients report experiencing TIA previously, suggesting that the incidence is actually much higher.1,4 It is likely that the incidence of TIA is underestimated because up to half of individuals who suffer TIAs do not seek medical attention.1,5


The incidence and prevalence of stroke in the United States can vary according to demographic factors, such as age, sex, ethnicity, geographic area, and education.1,27-29 The Southeast has been called the “stroke belt,” because all the states in this region, except Florida, have a rate of 55 to 65 stroke deaths per 100,000 persons ().1

Most strokes occur in individuals >65 years of age27; in the <40 years of age demographic, stroke prevalence is only 0.5%.1 In the 60- to 79-year age group, prevalence rises to more than 6%.1 In persons &#8805;80 years of age, 12.4% of women and 14.8% of men have suffered a stroke.1 The male-to-female incidence ratio is more than 1.0 for people aged 55 to 84 years, but it decreases to 0.76 in individuals &#8805;85 years of age.1 Women have 60,000 more strokes each year than men, which may be partly attributable to their longer life span,1 and this disparity between the sexes is growing. In the period between the 1988-1994 and 1999-2004 NHANES (National Health and Nutrition Examination Survey) surveys, the stroke rate tripled in women aged 35 to 54 years but remained the same in men of the same age group.28

Ethnic and racial minorities have an increased risk of stroke, and African Americans have almost twice as many first strokes as whites.1 Cumulative stroke incidence in Mexican Americans is 168 per 10,000 persons, compared with 136 per 10,000 in non-Hispanic whites.1

Morbidity and Mortality

Of the 55 million annual deaths worldwide, 10% are due to stroke.27 In the United States, 150,000 deaths from stroke occur each year&#8212;1 every 3 to 4 minutes.1 For 8% to 17% of ischemic stroke patients and 37% to 38% of hemorrhagic stroke patients, death occurs within 30 days of the incident.1,10 African Americans of both sexes and women die at much higher rates than white men.1 TIA patients also have a high mortality risk, and up to 25% will die within 1 year of a TIA.1 Although stroke mortality fell 24% from 1994 to 2004,1 stroke remains the third leading cause of death, just after heart disease and cancer.1,2,27

In addition to the burden of mortality, stroke is a leading cause of disability in the United States.1,2 It severely restricts functionality, contributes to high costs, and reduces a patient&#8217;s quality of life. More than 20% of stroke survivors will require institutional care within 3 months of the event.27 Direct medical costs related to stroke and indirect costs of lost productivity are expected to reach $65.5 billion in 2008.1

Risk Factors

Risk factors for recurrent stroke are the same as those for a first stroke, with one important addition: a previous stroke or TIA.1-4,8 Stroke survivors have a yearly 5% to 10% risk of having a second stroke.2 The rate of stroke recurrence within 5 years has ranged from 29% to 42%. This rate might be underestimated because some studies exclude recurrences soon after the index event,12 when the risk of a second event is greatest.17 About 15% of strokes are preceded by TIA.1,4 Patients have a 10.5% risk of suffering a stroke within 90 days of TIA. The 5-year risk of stroke for following TIA is 30%.2 Almost half of strokes that occur subsequent to TIA do so within 48 hours, which is an important reason why TIA should be considered a medical emergency requiring immediate evaluation.3,4,6-8 Imaging is useful in targeting which patients are most likely to benefit from preventive therapy.8 It has been shown that TIA patients with lesions on DWI have an even higher 90-day risk of subsequent stroke (10.8%), and those who have lesion and vessel occlusion have the highest risk, at 32.6%.8

Other factors are known to increase the risk of recurrent stoke in patients who have suffered previous stroke or TIA. An analysis of data from more than 18,000 patients in the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) trial found that high baseline leukocyte counts increased a patient&#8217;s risk of recurrent ischemic stroke, MI, or vascular death.33 Subsequent leukocyte counts significantly over baseline were associated with recurrent ischemic events within 1 week.33 In a study of 1707 patients with TIA, the significant independent risk factors for experiencing a stroke within 90 days included an age >60 years, diabetes, an episode of TIA lasting more than 10 minutes, and TIA symptoms of weakness, speech difficulty, and gait disturbance.4 Numbness, visual changes, and dizziness or vertigo were associated with lower stroke risk.4

Table 1

Table 2

Johnston and colleagues established and validated a scoring system (ABCD2) used to predict the risk of stroke at 2 days subsequent to TIA.9 The scoring system was also validated for time points at 7 and 90 days after presentation.9 The ABCD2 score evaluates 5 risk factors (Age, Blood pressure, Clinical features, Duration, Diabetes), and a score of 7 indicates highest risk ().9 ABCD2 helps identify those TIA patients who would benefit most from urgent intervention.9 Diener found slightly different predictors after index stroke and proposed a stroke recurrence prediction model based on a subgroup analysis of stroke patients in the CAPRIE trial.17 As with ABCD2, points are allotted for individual risk factors. Scores from 3 to 6 constitute high risk and scores from 7 to 10 indicate very high risk ().17

Many patients who suffer cerebrovascular events have systemic atherosclerosis.3 As a result, TIA or an initial stroke can also increase a patient&#8217;s risk for cardiovascular events,3,17 which are the cause of death in ~40% of stroke patients.3 In the first 10 years after ischemic stroke, more patients die from cardiovascular events than from initial or recurrent stroke.34 Following TIA, the patient has a 25% risk of MI or vascular death within the first 90 days.3 However, about 75% of the secondary events subsequent to a stroke are strokes.12 This suggests different cardiovascular and cerebrovascular pathogenetic mechanisms that favor recurrence of the same type of vascular event.35

Ischemic stroke is related to modifiable risk factors that have multiplied and compounded over years of life. Because patients who have experienced ischemic cerebrovascular events such as ischemic stroke or TIA are at high risk of suffering a second ischemic stroke, secondary stroke prevention to reduce modifiable risk factors is of paramount importance.

Need for Early Intervention

The American Heart Association/American Stroke Association has designed a program called Get With The Guidelines (GWTG)-Stroke to improve quality of care after TIA or stroke.1 GWTGStroke tracked the performance of 778 participating hospitals involving 141,449 patients admitted with ischemic stroke or TIA in 2006. The GWTGStroke observed the following regarding 7 key performance indicators1:

&#8226; 63% of patients who arrived at the hospital less than 2 hours after symptom onset received intravenous tPA

&#8226; 83% received deep vein thrombosis prophylaxis by the second day of hospitalization

&#8226; 98% received anticoagulation for atrial fibrillation at discharge

&#8226; 82% received cholesterol-lowering therapy at discharge if their low-density lipoprotein level was >100 mg/dL or if they were on therapy at admission

GWTG-Stroke concluded that the quality of hospital care, including secondary preventive care, was generally good for patients admitted for stroke symptoms. Challenges remain in ensuring continuity of care posthospitalization3 and especially in getting prompt care to all patients who experience cerebrovascular events. Stroke patients should receive immediate emergency evaluation, including neuroimaging and appropriate urgent therapy to halt neuronal damage, and long-term therapy to prevent future vascular events. TIAs are also medical emergencies, and patients who have one should seek medical attention as soon as possible. Primary care providers, in turn, should conduct full evaluations and send patients to the emergency department if they present within a few days of a suspected TIA or refer them to a neurologist if they present later.


2. Kelly BM, Pangilinan PH Jr, Rodriguez GM. The stroke rehabilitation paradigm. Phys Med Rehabil Clin N Am. 2007;18(4):631-650.

4. Johnston SC, Gress DR, Browner WS, Sidney S. Shortterm prognosis after emergency department diagnosis of TIA. JAMA. 2000;284(22):2901-2906.

6. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/ American Stroke Association Council on Stroke: cosponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37(2):577-617.

8. Coutts SB, Simon JE, Eliasziw M, et al. Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging. Ann Neurol. 2005;57(6):848-854.

10. Van der Worp HB, van Gijn J. Acute ischemic stroke. N Engl J Med. 2007;357(6):572-579.

12. Jamieson DG, Parekh A, Ezekowitz MD. Review of antiplatelet therapy in secondary prevention of cerebrovascular events: a need for direct comparisons between antiplatelet agents. J Cardiovasc Pharmacol Ther. 2005;10(3):153-161.

14. Liu Y, Mituska S, Hashizume K, Hosaka T, Nukui H. The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism. Acta Neurochir (Wien). 1997;139(8):770-779.

16. Kolominski-Rabas PL,Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001;32(12):2735-2740.

18. Fang MC, Stafford RS, Ruskin JN, Singer DE. National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. Arch Intern Med. 2004;164(1):55-60.

20. Suarez JI,Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354(4):387-396.

22. Jackson C, Sudlow D. Are lacunar strokes really different? A systematic review of differences in risk factor profiles between lacunar and nonlacunar infarcts. Stroke. 2005;36(4):891-901.

Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35-41.

25. Amarenco P, Cohen A,Tzourio C, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med. 1994;331(22):1474-1479.

27. Brass LM. Strategies for primary and secondary stroke prevention. Clin Cardiol. 2006;29(10 suppl):II21-II27.

29. Everson SA, Lynch JW, Kaplan GA, Lakka TA, Sivenius J, Salonen JT. Stress-induced blood pressure reactivity and incident stroke in middle-aged men. Stroke.

30. Sacco RL, Gan R, Boden-Albala B, et al. Leisure-time physical activity and ischemic stroke risk. The Northern Manhattan Stroke Study. Stroke. 1998;29(2):380-387.

32. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559.

34. Hardie K, Hankey GJ, Jamrozik K, Broadhurst RJ, Anderson C. Ten-year survival after first-ever stroke in the Perth Community Stroke Study. Stroke. 2003;34(8):1842-1846.

36. Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001;56(8):1015-1020.

38. Rothwell PM, Giles MF, Chandratheva A, et al; Early use of Existing Preventive Strategies for Stroke (EXPRESS) study. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective populationbased sequential comparison. Lancet. 2007;370(9596):1432-1442.