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Not-so-silent Stroke: Time to Make Some Noise

Disclosure: Dr. Elkind receives compensation for providing consultative services for Biotelemetry/Cardionet, BMS-Pfizer Partnership, Boehringer-Ingelheim, and Sanofi-Regeneron Partnership; receives compensation for serving as an expert witness in litigation for BMS-Sanofi (Plavix), Merck/Organon (Nuvaring), and Hi-Tech Pharmaceuticals (dimethylamylamine); receives royalties from UpToDate for chapters related to stroke; and serves on the National, Founders Affiliate, and New York City chapter boards of the American Heart Association/American Stroke Association.
Pub Date: Thursday, Dec. 15, 2016
Authors: Mitchell S. V. Elkind, MD, MS, FAAN, FAHA
Affiliation: Professor of Neurology and Epidemiology, Columbia University

Citation

Smith EE, Saposnik G, Biessels GJ, Doubal FN, Fornage M, Gorelick PB, Greenberg SM, Higashida RT, Kasner SE, Seshadri S; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Functional Genomics and Translational Biology; and Council on Hypertension. Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association [published online ahead of print December 15, 2016]. Stroke. doi: 10.1161/STR.0000000000000116.

Article Text

So-called “silent stroke” has been recognized as an entity since C. Miller Fisher reported in 1965, based on autopsy studies, that small infarcts occurred in the deep structures of the brains of patients without known symptoms.1  Research over the past several decades, however, has revealed that while such patients may not have reported clinical symptoms, these infarcts are usually not truly “silent,” since patients with these lesions frequently have evidence of cognitive, gait, or other functional impairment. Epidemiological studies have shown, moreover, that these patients are also at increased risk of future clinical stroke and dementia. Population-based studies using magnetic resonance imaging have also shown what Dr. Fisher, using detailed pathological study of post-mortem brains, could not: that these “silent” lesions are quite common in life. “Silent” infarcts, therefore, potentially pose an opportunity for intervention to prevent significant clinical complications, both for individuals and at the population level. Whether therapy focused specifically on patients with silent cerebrovascular disease can reduce the risk of adverse clinical outcomes is an attractive, if unproven, strategy, as detailed in a new scientific statement from the American Heart Association/American Stroke Association.2

Silent infarcts are not silent: Because silent brain infarcts are associated with several adverse neurological and cognitive outcomes, the terms “covert” or “subclinical” cerebrovascular disease may better represent the fact that these lesions have important clinical consequences.3  These consequences include impaired mobility, physical decline, depression, and cognitive dysfunction. In population-based studies, silent brain infarcts markedly increase risk of clinical infarction, by as much as 2-4 times in some studies.4,5  This increased risk, moreover, is independent of other risk factors for stroke, suggesting that silent infarcts provide an indicator of propensity for stroke not captured by existing risk factors. Observational studies have found lower levels of cognition among participants with evidence of silent brain infarction, and they appear to be associated with cognitive decline.6 Silent infarcts increase risk of mild cognitive impairment, and they double the likelihood of frank dementia, including Alzheimer disease as well as vascular dementia.7,8 Cerebral amyloid angiopathy (CAA), a small vessel vasculopathy due to deposition of a variant form of beta-amyloid in cerebral blood vessels, is often found in the brains of individuals with Alzheimer disease.9,10,11 Silent infarcts are associated with parkinsonism, as well, further illustrating the relationship between vascular and neurodegenerative disease of the brain.12 

Silent infarcts are common: The prevalence of silent infarcts ranges from approximately 10-30% in population-based studies.13 The differences across studies depend on several factors, including the methods of detection and the age, sex, and race-ethnicity of the individuals studied. MRI scanning is more sensitive for detection of silent infarcts than CT. Even high-resolution MRI, however, does not detect many “microinfarcts” visible at autopsy, though these subtle lesions may have clinical consequences when present in large numbers. The older the population, the higher the prevalence; silent infarcts are also 30-40% more prevalent in women than men. The prevalence of silent strokes, like clinical stroke, is also higher in certain minority groups. Among Japanese with a mean age of 59 years, the prevalence was 10%,14  while among those enrolled in the Cardiovascular Health Study (mean age 75, oversampled for African-Americans), the prevalence was 28%.15,16 Incidence studies provide further evidence of the burden of subclinical disease. Serial MRI scans in prospective cohorts indicate that up to 3% of elderly participants will develop new lesions annually.17,18,19

Silent infarcts are a measure of the increased burden of cerebrovascular disease: The recognition that silent infarcts are associated with clinical consequences and that they are common leads to the conclusion that the burden of cerebrovascular disease is even greater than previously thought. Since silent infarcts are about five times as prevalent as clinically apparent strokes, found in about 3% of the population, the inclusion of these lesions within the rubric of cerebrovascular disease indicates that approximately 15-20% of the population has vascular disease of the brain. As stroke has declined to the fifth leading cause of mortality in the US over the past decade, partly due to the efforts of the AHA/ASA, it is increasingly important to remain mindful of the fact that it is still the leading cause of long-term disability. Subclinical infarcts, while not fatal, contribute to this disability, and are thus responsible for an even greater burden of disability, including dementia, than previously realized.

Can silent infarcts be prevented?: Recognition of the significance of silent stroke raises the obvious question whether treatments can be applied to reduce their incidence, or whether therapeutic strategies known to reduce stroke risk should be applied in patients with silent stroke. Should patients with incidentally discovered silent infarcts be treated with antihypertensive agents or antiplatelets? Should the finding of silent infarcts be included in vascular risk prediction scores used by clinicians to determine when to start statins or other medications? At present, as this scientific statement makes clear,2 there are no well-conducted trials on which to base such recommendations. While it is probably reasonable to treat patients with subclinical disease aggressively to prevent the development of clinical disease, at present such decisions must be made on an individual basis, extrapolating cautiously from the available data. It is hoped, however, that future observational studies and trials will provide more definitive answers to these questions.

References

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  2. Smith EE, Saposnik G, Biessels GJ, Doubal FN, Fornage M, Gorelick PB, Greenberg SM, Higashida RT, Kasner SE, Seshadri S; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Functional Genomics and Translational Biology; and Council on Hypertension. Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association [published online ahead of print December 15, 2016]. Stroke. doi: 10.1161/STR.0000000000000116.
  3. Longstreth WT, Jr., Dulberg C, Manolio TA, Lewis MR, Beauchamp NJ, Jr., O'Leary D, Carr J, Furberg CD. Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke. 2002;33:2376-2382.
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-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --