EDITORIAL

Editorials represent the opinions

of the authors and JAMA and
not those of the American Medical Association.

Stroke in Young Adults

Implications of the Long-term Prognosis
Graeme J. Hankey, MD, FRCP, FRCP Edin, FRACP

TROKE IS NO LONGER CONSIDERED A DISEASE OF OLD

age. The mean age of stroke is declining and is now

69 years; the proportion of all strokes among persons younger than 55 years is increasing and is 19%;
and the incidence rates of stroke among 20- to 54-yearolds are increasing in the United States and United Kingdom and are 48 (95% CI, 42-53) per 100 000 population
among whites and 128 (95% CI, 106-149) per 100 000 population among blacks.1,2 Likely contributing factors are increasing diabetes; obesity; and recreational tobacco, drug,
and alcohol use,3,4 as well as enhanced detection among
younger people. The looming epidemic of stroke in young
adults has prompted the American Academy of Neurology
to set up a task force on stroke in young adults4 and the World
Stroke Organization to embark on a World Stroke Campaign that addresses the prevailing misconception that stroke
only happens later in life.5
But what do neurologists and other physicians know about
the outcome of young adults with stroke? In this issue of
JAMA, Rutten-Jacobs and colleagues6 report the long-term
mortality outcomes for 959 patients aged 18 through 50 years
admitted consecutively to a single academic medical center in the Netherlands between 1980 and 2010, diagnosed
with first-ever transient ischemic attack (TIA) or ischemic
or hemorrhagic stroke by means of standardized criteria, and
followed up, at a rate of 97%, over a mean of 11.1 years until 2012.
Among the 916 patients (95.5%) who survived more than
30 days after the index TIA, ischemic stroke, or intracerebral hemorrhage, mortality ranged from 1.2% to 2.9% at 1
year, 2.5% to 6.1% at 5 years, 9.2% to 12.4% at 10 years,
and 13.7% to 26.8% at 20 years.6 These rates were at least 3
times greater than the mortality rates of other, stroke-free,
adults of the same age, sex, and calendar year at risk in the
general population of the Netherlands, irrespective of the
pathologic type of stroke or the etiologic subtype of ischemic stroke. The relative excess of deaths among adults aged
18 through 50 years with stroke, compared with the general population, was greatest among the youngest individuals with stroke, but the absolute excess of deaths was highSee also p 1136.

est among older individuals with stroke. The excess mortality

relative to background mortality also persisted throughout
follow-up. However, the mortality risk was highest in the
first year after the index stroke and declined thereafter. Nevertheless, for individuals with TIA and ischemic stroke, as
opposed to hemorrhagic stroke, the annual mortality rate
began to increase again after a nadir at about 5 to 6 years
following the index event.6 This U-shaped pattern of annual mortality rates after TIA and ischemic stroke has been
described previously for both mortality and recurrent stroke
in the Dutch TIA trial cohort7 and for recurrent stroke in
the NASCET (North American Symptomatic Carotid Endarterectomy Trial) cohort,8 validating the observation and
raising the likelihood that many of the early deaths were attributable to, or associated with, early recurrent strokes.
Throughout follow-up, the causes of death were predominantly cardiovascular (cardiac, 26%; stroke, 19%; other vascular, 6%), as observed in other long-term follow-up studies of young adults with stroke,9-15 and indeed stroke at all
ages.16
These data suggest that patients with ischemic cerebral
events remain at increased risk of recurrent vascular events
and death for at least the next 10 to 20 years, and probably
throughout their life. Presumably this is because the cardiovascular disease or lesion underlying the index ischemic brain event (eg, valvular heart disease, atrial fibrillation, atherosclerosis) in some individuals remains active,
having not been diagnosed accurately and managed successfully. Another possibility is that lifestyle behaviors and
other risk factors that caused the cardiovascular lesion (eg,
smoking, alcohol and drug abuse, physical inactivity, hypertension) have not been eliminated or controlled.
Indeed, the strongest predictors of death among the young
adults with stroke were increasing age, cardiogenic sources
of cerebral embolism, and rare or coexisting causes of the
index ischemic stroke.6 Increasing age12,15 and cardiac diseases10 have also been reported as significant independent
predictors of long-term mortality in other cohorts of young
adults with stroke, as have male sex,12 large artery atherosclerosis causing the index event,9,12,15 coronary atheroscleAuthor Affiliations: School of Medicine and Pharmacology, University of Western Australia; and Department of Neurology, Royal Perth Hospital, Western Australia.
Corresponding Author: Graeme J. Hankey, MD, FRCP, FRCP Edin, FRACP, Department of Neurology, Royal Perth Hospital, 197 Wellington St, Perth, Western
Australia, 6001 (graeme.hankey@uwa.edu.au).

2013 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a Ondokuz Mayis niversitesi User on 11/11/2014

JAMA, March 20, 2013Vol 309, No. 11 1171

EDITORIAL

rosis,14 heart failure,15 traditional atherosclerotic risk factors,12 type 1 diabetes,13,15 heavy alcohol consumption,14,15
and malignancy.14,15 Moreover, an increasing number of traditional risk factors for stroke correlate with increasing noncerebrovascular events and mortality after stroke in young
adults.17
The validity of the results reported by Rutten-Jacobs et
al is supported by the rigorous study design and methods.
Although the results may be susceptible to hospitalreferral selection bias and random error (particularly for estimates of mortality after intracerebral hemorrhage, for which
there were few cases and deaths), the findings are generally consistent with those from other similar studies9-15 and
for the first time provide estimates of death rates among survivors of young adult stroke compared with the nationwide age- and sex-matched risk of dying.
The implications of these results for clinicians are that
adults younger than 50 years with stroke, particularly those
with cardioembolic ischemic stroke and other traditional risk
factors, need to be recognized as being at substantially higher
risk of death over the next 10 to 20 years than their fellow
community residents of the same age and sex who have not
had a stroke. To minimize the higher-than-expected mortality, the underlying cause of the stroke (eg, atherosclerosis, atrial fibrillation, valvular heart disease) and cause of
the symptomatic cardiovascular disease (eg, hypertension,
smoking, alcohol abuse) need to be diagnosed accurately
at presentation, treated appropriately, and, if possible, eliminated. If elimination of the cause is not possible, long-term
follow-up and control of the disease and its risk factors need
to be maintained vigilantly. Coexisting causes and risk factors also need to be either sought and eliminated or controlled over the long term. A recurrent stroke, particularly
of the same pathologic and etiologic type as the index stroke,
represents failed secondary prevention and is a further signal that the cause or causes of the index stroke have not been
diagnosed and managed successfully.
The implications for researchers of the results reported
by Rutten-Jacobs et al are that efforts to reduce the burden
of stroke among young adults should extend beyond acute
treatment and early secondary prevention into the long term.
Hence, studies evaluating the effectiveness, safety, and cost
of interventions to prevent recurrent cardiovascular events
and death among adults younger than 50 years with stroke
should acknowledge the continuing augmented risk of death

1172

JAMA, March 20, 2013Vol 309, No. 11

throughout subsequent decades and continue the intervention and follow-up in the long term, when substantial yields
are likely to be realized. The study by Rutten-Jacobs et al
indicates that secondary prevention after stroke in young
adults is a long-term, and probably lifelong, endeavor.
Conflict of Interest Disclosures: The author has completed and submitted the ICMJE
Form for Disclosure of Potential Conflicts of Interest and reported receiving honoraria from Bayer Pharmaceuticals for lectures at sponsored scientific symposia on
new oral anticoagulants for stroke prevention in atrial fibrillation.
REFERENCES
1. Rothwell PM, Coull AJ, Giles MF, et al; Oxford Vascular Study. Change in stroke
incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from
1981 to 2004 (Oxford Vascular Study). Lancet. 2004;363(9425):1925-1933.
2. Kissela BM, Khoury JC, Alwell K, et al. Age at stroke: temporal trends in stroke
incidence in a large, biracial population. Neurology. 2012;79(17):1781-1787.
3. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity
among US adults, 1999-2008. JAMA. 2010;303(3):235-241.
4. Sultan S, Elkind MS. Stroke in young adults: on the rise? Neurology. 2012;
79(17):1752-1753.
5. World Stroke Day 2013. World Stroke Organization website. http://www
.worldstrokecampaign.org/2012/About/Pages/WorldStrokeDay2013.aspx. Accessed
February 14, 2013.
6. Rutten-Jacobs LCA, Arntz RM, Maaijwee NAM, et al. Long-term mortality after stroke among adults aged 18 to 50 years. JAMA. 2013;309(11):1136-1144.
7. van Wijk I, Kappelle LJ, van Gijn J, et al; LiLAC Study Group. Long-term survival and vascular event risk after transient ischemic attack or minor ischemic stroke:
a cohort study. Lancet. 2005;365(9477):2098-2104.
8. Barnett HJ, Taylor DW, Eliasziw M, et al; North American Symptomatic Carotid Endarterectomy Trial Collaborators. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998;
339(20):1415-1425.
9. Kappelle LJ, Adams HP Jr, Heffner ML, Torner JC, Gomez F, Biller J. Prognosis
of young adults with ischemic stroke: a long-term follow-up study assessing recurrent vascular events and functional outcome in the Iowa Registry of Stroke in
Young Adults. Stroke. 1994;25(7):1360-1365.
10. Marini C, Totaro R, Carolei A; National Research Council Study Group on Stroke
in the Young. Long-term prognosis of cerebral ischemia in young adults. Stroke.
1999;30(11):2320-2325.
11. Marini C, Totaro R, De Santis F, Ciancarelli I, Baldassarre M, Carolei A. Stroke
in young adults in the community-based LAquila registry: incidence and prognosis.
Stroke. 2001;32(1):52-56.
12. Varona JF, Bermejo F, Guerra JM, Molina JA. Long-term prognosis of ischemic stroke in young adults: study of 272 cases. J Neurol. 2004;251(12):15071514.
13. Naess H, Nyland HI, Thomassen L, Aarseth J, Myhr KM. Long-term outcome
of cerebral infarction in young adults. Acta Neurol Scand. 2004;110(2):107112.
14. Waje-Andreassen U, Naess H, Thomassen L, Eide GE, Vedeler CA. Longterm mortality among young ischemic stroke patients in western Norway. Acta
Neurol Scand. 2007;116(3):150-156.
15. Putaala J, Curtze S, Hiltunen S, Tolppanen H, Kaste M, Tatlisumak T. Causes
of death and predictors of 5-year mortality in young adults after first-ever ischemic stroke: the Helsinki Young Stroke Registry. Stroke. 2009;40(8):2698-2703.
16. 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.
17. Putaala J, Haapaniemi E, Kaste M, Tatlisumak T. How does number of risk
factors affect prognosis in young patients with ischemic stroke? Stroke. 2012;
43(2):356-361.

2013 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a Ondokuz Mayis niversitesi User on 11/11/2014