Definition of TIA and Ischemic Stroke Subtypes

The distinction between TIA and ischemic stroke has become less important in recent years because many of the preventive approaches are applicable to both groups. They share pathogenetic mechanisms; prognosis may vary, depending on their severity and cause; and definitions are dependent on the timing and degree of the diagnostic evaluation. By conventional clinical definitions, if the neurological symptoms continue for > 24 hours, a person has been diagnosed with stroke; otherwise, a focal neurological deficit lasting < 24 hours has been defined as a TIA. With the more widespread use of modern brain imaging, many patients with symptoms lasting < 24 hours are found to have an infarction. The most recent definition of stroke for clinical trials has required either symptoms lasting > 24 hours or imaging of an acute clinically relevant brain lesion in patients with rapidly vanishing symptoms. The proposed new definition of TIA is a “brief episode of neurological dysfunction caused by a focal disturbance of brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of infarction.” TIAs are an important determinant of stroke, with 90-day risks of stroke reported as high as 10.5% and the greatest stroke risk apparent in the first week.

Ischemic stroke is classified into various categories according to the presumed mechanism of the focal brain injury and the type and localization of the vascular lesion. The classic categories have been defined as large-artery atherosclerotic infarction, which may be extracranial or intracranial; embolism from a cardiac source; small-vessel disease; other determined cause such as dissection, hypercoagulable states, or sickle cell disease; and infarcts of undetermined cause. The certainty of the classification of the ischemic stroke mechanism is far from ideal and reflects the inadequacy or timing of the diagnostic workup in some cases to visualize the occluded artery or to localize the source of the embolism. Recommendations for the timing and type of diagnostic workup for TIA and stroke patients are beyond the scope of this guideline statement.

Risk Factor Control for All Patients With TIA or Ischemic Stroke

Hypertension
It is estimated that ~50 000 000 Americans have hypertension. There is a continuous association between both systolic and diastolic blood pressures (BPs) and the risk of ischemic stroke. Meta-analyses of randomized controlled trials confirm an approximate 30% to 40% stroke risk reduction with BP lowering. Detailed evidence-based recommendations for the BP screening and treatment of persons with hypertension are summarized in the American Stroke Association Scientific Statement on the Primary Prevention of Ischemic Stroke and the AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update and are detailed in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7). JNC-7 stresses the importance of lifestyle modifications in the overall management of hypertension. Systolic BP reductions have been associated with weight loss; the consumption of a diet rich in fruits, vegetables, and low-fat dairy products; regular aerobic physical activity; and limited alcohol consumption.

Although a wealth of data from a variety of sources support the importance of treatment of hypertension for primary cardiovascular disease prevention in general and in stroke in particular, only limited data directly address the role of BP treatment in secondary prevention among persons with stroke or TIA. There is a general lack of definitive data to help guide the immediate management of elevated BP in the setting of acute ischemic stroke; a cautious approach has been recommended, and the optimal time to initiate therapy remains uncertain.

A systematic review focused on the relationship between BP reduction and the secondary prevention of stroke and other vascular events. The analysis included 7 published, nonconfounded, randomized controlled trials with a combined sample size of 15 527 participants with ischemic stroke, TIA, or ICH randomized from 3 weeks to 14 months after the index event and followed up for 2 to 5 years. No relevant trials tested the effects of nonpharmacological interventions. Treatment with antihypertensive drugs has been associated with significant reductions in all recurrent strokes, nonfatal recurrent stroke, MI, and all vascular events with similar, albeit nonsignificant, trends toward a reduction in fatal stroke and vascular death. These results were seen in studies that recruited patients regardless of whether they had hypertension.

Diabetes
Diabetes is estimated to affect 8% of the adult population. It is frequently encountered in stroke care, being present in 15%, 21%, and 33% of patients with ischemic stroke. Diabetes is a clear risk factor for stroke. The data supporting diabetes as a risk factor for recurrent stroke, however, are more sparse. Diabetes mellitus (DM) and age were the only significant independent predictors of recurrent stroke in a population-based study of stroke from Rochester, Minn. In another community-based stroke study, the Oxfordshire Stroke Project, diabetes was 1 of 2 factors independently associated with stroke recurrence (hazard ratio [HR] 1.85; 95% CI, 1.18 to 2.90; P<0.01), and investigators estimated that 9.1% (95% CI, 2.0 to 20.2) of the recurrent strokes were attributable to diabetes. In the evaluation of 2-year stroke recurrence in the Stroke Data Bank, patients at the lowest risk had no history of diabetes. Furthermore, diabetes has been shown to be a strong determinant for the presence of multiple lacunar infarcts in 2 different stroke cohorts.

Most of the available data on stroke prevention in patients with diabetes are on the primary rather than secondary prevention of stroke. Multifactorial approaches with intensive treatments to control hyperglycemia, hypertension, dyslipidemia, and microalbuminuria have demonstrated reductions in the risk of cardiovascular events. These intensive approaches included behavioral measures and the use of a statin, ACEI, ARB, and antiplatelet drug as appropriate. Primary stroke prevention guidelines have emphasized the more rigorous control of BP among both type 1 and type 2 diabetics with lower targets of 130/80 mm Hg. Tight control of BP in diabetics has been shown to reduce the incidence of stroke significantly. In the United Kingdom Prospective Diabetes Study (UKPDS), diabetic patients with controlled BP (mean BP, 144/82 mm Hg) had a 44% reduced relative risk (RR) of stroke compared with diabetics with poorer BP control (mean BP, 154/87 mm Hg; 95% CI, 11 to 65; P=0.013). Intensive treatment of hypertension also significantly reduced the risk of the combined end point of MI, sudden death, stroke, and peripheral vascular disease by 34% (P=0.019). Additional clinical trials have corroborated the risk reduction in stroke and/or cardiovascular events with BP control in diabetics. Although most of these studies did not reach the goal BP of 130/80 mm Hg, epidemiological analyses suggest a continual reduction in cardiovascular events to a BP of 120/80 mm Hg.

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Ralph L. Sacco, MD, MS, FAHA, FAAN, Chair; Robert Adams, MD, FAHA, Vice Chair; Greg Albers, MD; Mark J. Alberts, MD, FAHA; Oscar Benavente, MD; Karen Furie, MD, MPH, FAHA; Larry B. Goldstein, MD, FAHA, FAAN; Philip Gorelick, MD, MPH, FAHA, FAAN; Jonathan Halperin, MD, FAHA; Robert Harbaugh, MD, FACS, FAHA; S. Claiborne Johnston, MD, PhD; Irene Katzan, MD, FAHA; Margaret Kelly-Hayes, RN, EdD, FAHA; Edgar J. Kenton, MD, FAHA, FAAN; Michael Marks, MD; Lee H. Schwamm, MD, FAHA; Thomas Tomsick, MD, FAHA

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Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack