August 3, 2007 — A report from the ongoing Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study shows that individuals with symptoms consistent with stroke, but no previous stroke diagnosis, show reductions in quality-of-life parameters, including physical functioning and, to a lesser extent, mental functioning, compared with those without such symptoms.

"What we're trying to say is what we've been calling silent strokes really might not be all that silent," lead author George Howard, DrPH, from the School of Public Health at the University of Alabama, Birmingham, told Medscape.

Their findings are published online in the August 2 Stroke ASAP issue, in advance of print publication in the September issue of Stroke.

Whispering Stroke

Strokes that are evident on brain imaging but do not produce symptoms are known as "silent" strokes. However, some of these so-called silent strokes may be accompanied by mild symptoms or deficits, Dr. Howard noted.

The authors propose instead the term "whispering" stroke, which Dr. Howard credits to coauthor James F. Meschia, MD, of Mayo Clinic in Jacksonville, Florida. The authors write, "that is, they could have clinically consistent symptoms that fail to result in a diagnosis of stroke or transient ischemic attack (TIA) either through the symptoms being insufficiently pronounced or persistent to raise concerns in the participant; or if clinical care was sought, the symptoms were not sufficiently defined to result in a diagnosis of stroke."

"Nevertheless, these symptoms could still be associated with potential subclinical deficits detected by systematic testing, and these subclinical deficits could be associated with a substantial population-level public health burden," they add.

This is the third in a series of reports from the REGARDS cohort looking at the occurrence of stroke symptoms in the absence of a diagnosis of stroke or TIA. The first of these, by Howard and colleagues and published in the October 9, 2006, issue of Archives of Internal Medicine, showed that, when screened actively, almost 18% of participants reported at least 1 stroke symptom without ever having had a stroke diagnosed, and those with more stroke risk factors were more likely to report stroke symptoms.

A second REGARDS study, by Wadley and colleagues and in press for publication in Stroke, showed that subjects with these stroke symptoms were twice as likely to show cognitive impairment as those without symptoms despite having no stroke diagnosis.

This third paper from the REGARDS group looks at quality of life in these subjects with stroke symptoms in the absence of recognized stroke. A large national cohort study, REGARDS includes black and white individuals older than 45 years. The researchers compared the average physical and mental functioning of 3404 subjects who had reported symptoms of stroke but had not had a clinical stroke diagnosed with those of individuals who had no symptoms of TIA or stroke (n = 16,090), who had a history of stroke (n = 1491), or who had a history of TIA (n = 818).

They assessed quality of life using the Physical and Mental Component Summary scores of the Short Form 12 (PCS-12 and MCS-12).

Ischemic Attacks, Not Transient?

The researchers report that, compared with those subjects without symptoms or a diagnosis of stroke, those with stroke symptoms but no diagnosed stroke had mean PCS-12 scores that were 5.5 points lower, a reduction similar to that seen in the group that had already had a TIA, where average PCS-12 scores were 6.0 points lower. This reduction constituted more than half of the effect of an actual clinical stroke, where patients with stroke had a PCS-12 score that averaged 8.4 points lower than those without any symptoms.

Differences in average MCS-12 scores were smaller but still significant; those with stroke symptoms but no diagnosed stroke had mean MCS-12 scores that were 2.7 points lower than those of individuals without symptoms. This difference was larger than that seen between symptom-free subjects and those with a history of TIA but no current symptoms, and those with a history of stroke but no current symptoms.

The differences were not fully explained by differences in demographic and vascular risk factors, health behaviors, physiological measures, and indices of socioeconomic status, they write.

Subjects who had reported symptoms of weakness or numbness had larger current decrements in physical functioning scores, and those who had reported an inability to express themselves or understand language had larger current deficits in mental functioning, they note.

When these findings are considered along with those in the 2 previous REGARDS reports, Dr. Howard said, "what's developing is a picture that suggests, at least in my opinion, that these symptoms were small strokes that were either blown off by the participant or blown off by the doctor, and are really more important than people are giving them credit for."

The REGARDS group will be following this cohort to see whether those with stroke symptoms are at higher risk for clinical stroke, he said. "But if I were a betting man, I would bet that, just like people who have already had a TIA are at extraordinary risk for subsequent stroke, these people are going to be at extraordinary risk for subsequent stroke because frankly, I think what they are is undiagnosed TIAs."

It could be argued further that these TIAs are not transient at all. "If your cognitive functioning is impaired and your quality of life is impaired, some people would argue that that is symptomatic," he said.

This study was supported by a cooperative agreement from the National Institute of Neurological Disorders and Stroke. The authors have disclosed no relevant financial relationships.

Stroke. Published online August 2, 2007.

Clinical Context

Study Highlights

• The study cohort was drawn from the REGARDS project. Black and white adults in the United States older than 45 years were eligible for study participation, and researchers focused on recruitment from the American "stroke belt" in the south.
• A history was completed via telephone interview, and a physical examination was completed, along with laboratory assessment and electrocardiography, in the study subjects' home. Participants completed the PCS-12 and MCS-12, and any history of cerebrovascular disease was measured by patient self-report. The Questionnaire for Verifying Stroke-Free Status was used to assess stroke symptoms.
• Subjects were divided into those reporting a history of stroke; a history of TIA; stroke symptoms without a history of stroke or TIA; and no history of stroke, TIA, or stroke symptoms. The main study outcome was mental and physical well-being among subjects with and without a history of stroke or TIA. This result was adjusted for demographic, socioeconomic, and fitness variables as well as cardiovascular risk factors.
• The study cohort comprised 21,959 participants. Slightly more than half of subjects were women, and slightly more than 40% were black. The mean age of participants was 66 years.
• The numbers of participants reporting no stroke or TIA and no symptoms, symptoms without prior stroke or TIA, a history of TIA, and a history of stroke were 16,090, 3404, 818, and 1491, respectively.
• Compared with subjects reporting no symptoms and no history of stroke or TIA, participants with symptoms and no history of stroke or TIA had a mean reduction in the PCS-12 score of 5.5. This decrement was similar to that associated with a history of TIA (-6.0) but lower than that associated with stroke (-8.5). The adjusted result demonstrated a significant difference between subjects with and without stroke symptoms in physical functioning.
• Mental health functioning was not as negatively affected by stroke symptoms as physical functioning, but there was still a significant adjusted decline in MCS-12 scores among subjects with vs without stroke symptoms. The slight reduction in mental health functioning among participants with stroke symptoms but no history of stroke or TIA was similar to the reduction associated with TIA and stroke.
• Among individual symptoms, unilateral numbness and weakness had a particularly negative effect on physical functioning. Meanwhile, the inability to understand others and the inability to express oneself were the factors most likely to reduce MCS-12 scores.

Pearls for Practice

• Silent strokes detectable only on brain imaging are common in older adults and increase the risk for cognitive decline and subsequent clinically pronounced stroke.
• The current study shows that stroke symptoms of stroke in the absence of known stroke or TIA reduce physical functioning and, to a lesser extent, mental health functioning.

CME Test