Saturday, February 7, 2015

Stroke in Young Adults: Risk Factors and Prognosis



Stroke is often considered an older person's disease, but an estimated 10% of stroke patients are younger than 50. Recent reports show an apparent increasing trend in ischemic stroke among young adults, a figure that is particularly concerning when compared to the overall decrease in stroke incidence and mortality. Although certain rare risk factors have been suggested as possible causes, reports show that traditional risk factors for stroke actually may be overlooked in this population. (published site)
While the absolute numbers are small — with an average of 2,868 deaths per year attributed to stroke in young adults between 1989 and 2009 — the lifetime impact of stroke on young adults carries substantial costs to the individual's family and to society, according to Sharon Poisson, MD, assistant professor in the department of neurology at the University of Colorado.
“We recently completed a study looking at mortality from different kinds of stroke over a 20-year period, and while mortality from ischemic stroke dropped by more than 50% over that time period in older adults, it actually rose a little in young adults. It isn't clear whether there truly is a rise in mortality among young adults or if it has remained the same,” Dr. Poisson says. “Either way, there is a big difference between what is happening in older adults and what is happening with mortality from ischemic stroke in younger adults.”
In the study, Poisson's team found that stroke mortality in young adults remains rare —  in the range of .93 per 100,000 population for intracranial hemorrhagic stroke to .70 per 100,000 for ischemic stroke. However, while hemorrhagic stroke in young adults declined during that period, ischemic stroke increased by 11% from .60 to .67 per 100,000 person years.1
A 2014 Finnish study of 970 young adult stroke patients showed that after a mean follow-up period of 10.2 years, the observed mortality for young adult stroke patients was sevenfold higher than the expected mortality in the general population.2 After adjusting for demographics, risk factors, and stroke characteristics, having a recurrent stroke more than doubled the cumulative mortality rate and raised the hazard of death in such patients to approximately 17 times higher than in those with only a single episode of stroke.3

Risk Factors

Until recently, stroke in young adults had been thought to be associated with rare risk factors, including arterial dissection, reversible cerebral vasoconstriction syndrome, inflammatory arteritis, cardiomyopathy, and several hypercoagulable factors.
But according to Steven Kittner, MD, professor of neurology at University of Maryland, the evidence actually undermines the role of hypercoagulable conditions in the vast majority of early onset strokes, as is the case for prothrombin mutation and Factor V Leiden. The one exception is for those with a cerebral venous thrombosis.
“I think there is a misunderstanding among physicians that hypercoagulable states are very important to screen for in every early onset stroke case as a mark of quality and thoroughness,” Kittner said. “I think we should be much more selective because in over 25 years of seeing a large number of early onset strokes, I can count on the fingers of one hand the patients who had arterial ischemic stroke that was due to a hypercoagulable condition.”
A review in Nature Reviews Neurology found that although the role of rare risk factors in the pathophysiology of young stroke seems overestimated, the role of traditional vascular risk factors may have been underestimated. And the rising incidence of stroke in young adults coincides with an increasing prevalence of traditional vascular risk factors in this age group, although they note that causality has yet to be proven.4
Researchers noted that primary risk factors associated with the highest five-year risk of recurrent stroke included the traditional vascular risk factors, including being older than 40, having a history of transient ischemic attack or type 1 diabetes, and taking anti-hypertensive medication. In addition, the studies reviewed showed that mortality risk also increased with the number of traditional cardiovascular risk factors.5
As for genetic risk factors, the Genetics of Early Onset (GEOS) stroke meta-analysis looked at G20210A mutations in 397 first-ever ischemic strokes in a European population. It also included a meta-analysis of 17 case-control studies involving another 2,305 cases. The analysis failed to show statistical significance for an association of the prothrombin G20210A mutation with ischemic stroke in young adults of European ancestry, and there was no association with cryptogenic stroke or those with cardiovascular risk factors as stratified individually or when analyzed in aggregate.4

Prognosis

Aside from mortality, long-term prognosis for early onset stroke appears to be somewhat more severe than previously thought. Although there is a lot of anecdotal evidence that young adults do better after a stroke than older stroke patients, compared with the general population of the same age, young adult stroke patients experience higher death rate, higher risk of cardiovascular events, and significant limitations in quality of life.
The Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study of long-term functional outcome after stroke among adults 18 to 50 years found that by two functional measures —the modified Rankin Scale (mRS) and the Instrumental Activities of Daily Living (iADL) scale — many patients continued to have poor functional outcomes an average of nine years after stroke.5
“We showed that even after 10 years, about 1 of 8 patients (12.9%) with an ischemic or intracranial hemorrhagic stroke at young age was not able to function independently. In patients with transient ischemic stroke, this was 1 of 15 (6.5%) survivors,” the authors wrote.
Poisson said functional outcomes, however, may not be enough to measure the full impact of stroke in young adults. “What is missed is can they live a normal life? Can they keep their jobs, raise their kids? Can they support their families?” she said. “Those are significant to young adults in the situations they are in, and stroke absolutely affects that over their lifetime.”

Prevention

In terms of addressing the trend and taking stroke prevention measures aimed at young adults, the key may lie in changing the mindset that stroke is a disease of older people.
“One of the big questions that comes up is, ‘Are we missing atherosclerotic risk factors in young adults?'” Poisson said. “We need to recognize that stroke is not just a disease of older adults. It happens across the entire age spectrum, and it is really important to be aware of that so we can think about prevention, recognize stroke when it happens, and treat it urgently to minimize future disability.” 
Kittner agreed, noting that there has been a lot of under-recognition by emergency medical providers because early onset stroke is rare, and it is often not appreciated that otherwise healthy young people can have a stroke.
“The other take-home message,” Kittner said, “is that traditional risk factors should be managed aggressively, and I think the role of the obesity epidemic on future vascular disease and the increasing risk of vascular disease in younger adults is a disturbing trend and should reinforce health efforts to reduce the obesity epidemic.”
Kittner also emphasized that every young adult stroke patient should have a toxicology screen because you can't tell who is abusing drugs from the patient's demographic profile.
“It is very prevalent, and if you don't [do] a toxicology screen on admission, you may miss an important modifiable factor for the cause of the stroke,” Kittner said.
Michael O'Leary is a freelance medical writer based in the greater Seattle area. This article was medically reviewed by Pat F. Bass III, MD, MS, MPH.

References

  1. Poisson SN, Glidden D, Johnston SC, Fullerton HJ. Deaths from stroke in US young adults, 1989-2009. Neurology. 2014;83(23):2110-5.
  2. Aarnio K, Haapaniemi E, Melkas S, Kaste M, Tatlisumak T, Putaala J. Long-term mortality after first-ever and recurrent stroke in young adults. Stroke. 2014;45(9):2670-6.
  3. Maaijwee NA, Rutten-jacobs LC, Schaapsmeerders P, Van dijk EJ, De leeuw FE. Ischaemic stroke in young adults: risk factors and long-term consequences. Nat Rev Neurol.2014;10(6):315-25.
  4. Jiang B, Ryan KA, Hamedani A, et al. Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis. Stroke. 2014;45(4):961-7.
  5. Synhaeve NE, Arntz RM, Maaijwee NA, et al. Poor long-term functional outcome after stroke among adults aged 18 to 50 years: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study. Stroke. 2014;45(4):1157-60.

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