Young Stroke Survivors Face Increased Long-Term Death Risk

Damian McNamara

May 29, 2019

MILAN — New findings add to growing evidence of long-term mortality hazards among young stroke survivors.

The results show the risk of death remained elevated up to 15 years later following a first-time ischemic stroke or intracerebral hemorrhage (ICH) among people whose first stroke occurred at ages 18 to 49.

Both men and women who survived at least 30 days after an ischemic stroke had a 5.1 times higher risk of death during an average 9.3 years of follow-up compared with the general population. Short-term survivors of an ICH had an even greater mortality risk — 8.4 times higher than the general population.

"Approximately 10% to 15% of all strokes occur in young adults, 18 up to 50 years old," said Jamie Verhoeven, Bsc, a medical student at the Donders Institute for Brain, Cognition, and Behaviour, and Radboud University Medical Centre in the Netherlands. "We also know the incidence is on the rise, making this subgroup even more important at the moment."

Verhoeven presented the findings here at the 5th European Stroke Organisation Conference (ESOC) 2019. The study was concurrently published online May 23 in JAMA.

Even though previous researchers have evaluated stroke outcomes in young adults, mortality data in this group "are very limited," she said. Small study populations, use of only hospital-based cohorts or long inclusion periods — "some even spanning decades" — are among the limitations of earlier studies.

Verhoeven, with lead author Merel Sanne Ekker, MD, and colleagues assessed data for 15,257 stroke survivors to determine all-cause mortality over time. Patients were included if they experienced a first ischemic stroke or ICH between 1998 and 2010, with a follow-up through 2016 to assess mortality rates.

The researchers identified patients using ICD-9 and ICD-10 codes in the national Hospital Discharge Registry, deaths using the national Cause of Death Registry, and identified age- and sex-matched controls using the Dutch Population Register.

The study population was 53% women and mean age was 42 years. A total of 55% experienced an index ischemic stroke, 20% had an ICH, and 25% experienced a stroke not otherwise specified.

At end of follow-up, 3540 cumulative deaths had occurred, including 1776 deaths within 30 days after stroke and 1764 deaths (23.2%) over a median follow-up of 9.3 years (interquartile range, 5.9 to 13.1 years).

The 15-year mortality in 30-day survivors was 17.% (95% confidence interval [CI], 16.2% - 17.9%). The standardized mortality rate compared with the general population was 5.1 (95% CI, 4.7 - 5.4) for ischemic stroke (observed mortality rate 12.0/1000 person-years [95% CI, 11.2 - 12.9/1000 person-years]; expected rate, 2.4/1000 person-years; excess rate, 9.6/1000 person-years)

The standardized mortality rate for ICH was 8.4 (95% CI, 7.4 - 9.3; observed rate, 18.7/1000 person-years [95% CI, 16.7 - 21.0/1000 person-years] vs expected rate of 2.2/1000 person-years; excess rate, 16.4/1000 person-years).

Sex Differences

Even though all ischemic stroke survivors had an elevated risk of long-term death, the risk was significantly higher among men. During the study period, 22% of men in this group died (vs 14.5% of women). The difference was statistically significant (P < .01).

Among the ICH survivors, 24% of men and 18% of women died during follow-up (P < .01).

Overall, compared with women, men had a greater likelihood of death during the study period (hazard ratio, 1.4; 95% CI, 1.3 - 1.6) using a Cox Proportional Hazard Model.

The investigators also found older patients in this population of 18 to 49 year olds were at a higher risk for long-term mortality. Compared to a reference group of 18 to 24 year olds, for example, those ages 35 to 39 years had a hazard ratio of 2.3 (95% CI, 1.4 - 3.6).

"This risk increased for every year the patients were older," Verhoeven said. The hazard ratio in the 40- to 44-year-old cohort was 2.5 (95% CI, 1.6 - 4.0) and in the 45- to 49-year-old group it was 3.4 (95% CI, 2.3 - 5.3).

In terms of a bigger picture, the researchers also evaluated temporal trends in mortality through the study period. For both ischemic stroke and ICH, they found a clear decrease from 1998 to 2010 that was significant for both men and women.

More recent reductions in mortality among those with ischemic stroke in particular could be "due to better diagnosis strategies that have become available for these patients… [leading to] faster and more adequate treatment," Verhoeven said.

Important Study

"I think it's an important study [that includes] a fairly large cohort of patients," session co-moderator Joji B. Kuramatsu, MD, of the Department of Neurology at the Friedrich-Alexander-University of Erlangen-Nuremberg in Germany, told Medscape Medical News when asked to comment.  

The incidence rates, he noted, are very coherent to what is already known from the global stroke perspective (and published in various Lancet publications) and align with other findings in the Western Hemisphere.

The study was funded by grants to individual investigators from the Dutch Heart Foundation, the Netherlands Organisation for Health Research and Development, and the Netherlands ZonMw. Verhoeven and Kuramatsu have disclosed no relevant financial relationships.

5th European Stroke Organisation Conference (ESOC) 2019.
Presented May 24, 2019.

JAMA. Published online May 23, 2019. Full text

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