Transient Ischemic Attack: Short-Term and Long-Term Risk Factor for Stroke

Abstract & Commentary

By Dana Leifer, MD, Associate Professor of Neurology, Weill Medical College of Cornell University. Dr. Leifer reports no consultant, stockholder, speaker’s bureau, research, or other financial relationship related to this field of study.

Synopsis: Patients who have had a transient ischemic attack have not only a high short-term chance of ischemic stroke but also a long-term risk of vascular events over 10 years or more.

Source: van Wijk I, et al. Long-Term Survival and Vascular Event Risk After Transient Ischaemic Attack or Minor Ischaemic Stroke: A Cohort Study. Lancet. 2005;365: 2098-2104.

Although the symptoms of transient ischemic attack (TIA) are often minor and fleeting, several studies have demonstrated that TIAs should be taken seriously and evaluated quickly because of the short-term risk of potentially devastating ischemic stroke. Johnston and colleagues reported that, in a cohort of 1707 TIA patients, 5.3% had a stroke within 48 hours and an additional 5.3% had a stroke between 2 and 90 days after the presenting TIA (JAMA. 2000;284:2901-2906). Moreover, Rothwell and colleagues demonstrated in a study incorporating results from 2 population-based studies and 2 randomized clinical trials that 15% to 26% of stroke patients had a preceding TIA. Of the patients who had a TIA, 17% occurred on the day of the stroke, 9% on the day before the stroke, and an additional 19% between 2 and 7 days before the stroke (Neurology. 2005;64:817-820).

In addition, multiple studies have indicated that 35% to 67% of ischemic episodes producing only transient signs and symptoms are actually associated with evidence of acute infarction, when MRI studies with diffusion-weighted imaging (DWI) is performed. A recent report by Ay and colleagues studied a group of 87 patients with transient ischemic symptoms, of whom 36 had DWI-positive infarcts. They suggest that transient symptoms (less than 24 hours in duration) with a DWI-positive infarct may represent a particularly unstable problem, with an 8.3% risk of stroke during the admission for the transient symptoms (Ann Neurol. 2005;57:679-686). In contrast, none of their patients with TIA and normal DWI had a stroke before discharge from the hospital. Only 1.3% of a control group of patients with clinical stroke syndromes, who had symptoms lasting longer than 24 hours, had a second stroke while hospitalized.

Taken together, these studies strongly suggest that rapid evaluation and treatment of patients with transient ischemic symptoms is appropriate in an attempt to reduce the short-term risk of stroke. Furthermore, a MRI to screen for DWI-positive lesions may be useful to identify high-risk patients.

A recent paper by van Wijk and colleagues (Lancet. 2005;365:2098-2104) provides additional information about the natural history of TIA and minor ischemic stroke over the long-term. They followed 2447 patients with TIA or minor ischemic stroke who had been enrolled in the Dutch TIA trial (DTT). This trial compared 30 mg of aspirin daily to 283 mg for up to 4 years. After the end of the DTT, patients resumed standard medical care. van Wijk et al now report that the 10-year risk of vascular events was 35.8% for TIA patients and 47.8% for patients with minor stroke. They do not report whether any of the TIA patients had DWI-positive infarcts on MRI.

van Wijk et al do report the time course of events for stroke and TIA patients combined, but not for TIA patients alone. The annual risks of stroke and other vascular events declined from 4.6% and 2.4%, respectively, in the first year, to approximately 1.0% and 2.5%, respectively, in the third year. The rates then gradually rose to about 2% and 5%, respectively.

The results suggest that the relative risk of recurrent stroke and other vascular events changes over time. The risk of stroke is greatest at first, then declines, and then after the first 3 years increases slowly. The risk of over vascular events also declines over the first 3 years, and then gradually increases and becomes greater than the risk of stroke.

van Wijk et al do not provide a definitive explanation for these results, but they do propose several plausible hypotheses. They suggest that the decreased risk in the first 3 years could reflect antiplatelet therapy and better control of risk factors during the trial, and increased risk after 3 years could reflect changes in management and in closeness of follow-up after the end of the Dutch TIA trial (DTT). Stabilization of plaque that caused the initial ischemic event could also explain the drop in stroke rate over time, whereas the increased rate of other ischemic events could reflect progression of underlying atherosclerosis.

In any case, ongoing efforts to manage vascular risk factors such as hypertension, diabetes, and hypercholesterolemia appear to be important for years after a TIA or minor stroke. Each of these risk factors was found to be associated with a significantly increased risk of major vascular events in general, and hypertension and diabetes were also associated with a significantly increased risk of stroke in particular.

In conclusion, there is now evidence not only that prompt evaluation of patients with transient ischemic syndromes is needed to attempt to reduce the incidence of stroke acutely, but also that ongoing follow-up is important and should focus on risk factor management to reduce the chance of ischemic events of all types in the long run.