Nontraditional Risk Factors More Likely to Cause Stroke in Young Adults, Study Finds

Nontraditional risk factors for stroke may contribute to more cerebrovascular events among young adults (aged 18 to 34 years) than traditional risk factors, according to findings of a new retrospective case control study.¹

Stroke was associated with nontraditional risk factors, eg, migraine, kidney failure, autoimmune disease, and thrombophilia, in approximately 31% of young men in the study and 43% of young women compared with traditional risk factors, eg, hypertension, hyperlipidemia, type 2 diabetes, which accounted for stroke in 25% among the men and 33% in the women.

Michelle Leppert, MD
CU School of Medicine

The researchers, led by Michelle Leppert, MD, assistant professor of neurology and the University of Colorado School of Medicine, in Aurora, CO, also found that nontraditional risk factors contribute less to stroke risk with age, while the contribution of traditional risk factors peaks among individuals aged 35 to 44 years.¹

The findings were published online on March 26, 2024, in Circulation: Cardiovascular Quality and Outcomes.

The incidence of stroke among adults younger than age 45 years has increased steadily over the past 2 decades in high income countries, the authors wrote, while the incidence in those older than 45 years has decreased. Leppert and colleagues cite research findings that have kept clinical focus and intervention and prevention efforts trained on the contribution of traditional risk factors. More recent data, however, show an increased incidence of stroke even among young adults without these risk factors. Moreover, even though women have fewer traditional risk factors, strokes are more common among women than men who are aged 45 years or younger.¹

"The younger they are at the time of stroke, the more likely their stroke is due to a nontraditional risk factor," Leppert said in a news release.²

For the case control study, researchers used the state of Colorado’s All Payer Claims Database, extracting data from 2012 to 2019. They identified index stroke events in young adults (aged 18 to 55 years) that resulted in inpatient admission and matched those individuals in a 1:3 ratio to controls without stroke by sex, age, and insurance type. All the traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date.¹ Leppert and team defined traditional risk factors as “a well-established risk factor for stroke that is routinely considered during the stroke workup for older adults,” including hypertension, diabetes, hyperlipidemia, sleep apnea, cardiovascular disease, alcohol, substance use disorder, and obesity.¹ Nontraditional risk factors were defined as those that are rarely cited as a cause of stroke in older adults and included migraines, malignancy, HIV, hepatitis, thrombophilia, autoimmune disease, vasculitis, sickle cell disease, heart valve disease, renal failure, and hormonal risk factors in women.

FINDINGS¹

Total stroke cases numbered 2618 (52% women; 73.3% ischemic strokes) and were matched with 7827 controls. The researchers reported that all traditional risk factors were more prevalent among cases than controls. Overall, Leppert and colleagues found that traditional risk factors were more common among stroke cases. Among adults aged 18 to 34 years, however, more strokes were associated with nontraditional (31.4% men, 42.7% women) than traditional risk factors (25.3% men, 33.3% women). Nontraditional risk factors became less prevalent with age and after age 44 years were no longer significant, according to the findings. Hypertension was the most important traditional risk factor among both men (44.3%) and women (41.6%) and the contribution to risk increased with age.

The finding that migraine was the most important nontraditional risk factor, although contribution declined with age, was unexpected, said Leppert in the news release. “There have been many studies demonstrating the association between migraines and strokes, but to our knowledge, this study may be the first to demonstrate just how much stroke risk may be attributable to migraines.”

More results are highlighted below.

Leppert et al said that each additional traditional and nontraditional risk factor was associated with increased risk of stroke across age groups and sex.

“Contrary to our hypothesis, nontraditional risk factors were equally important to the development of strokes in young men and women…In adults aged 18 to 34 years, more strokes were associated with nontraditional than traditional risk factors," the authors wrote. "These findings underscore the importance of also considering nontraditional risk factors in the etiologies of strokes, among young adults.

"Further research is warranted to better understand how migraines contribute to the risk of strokes among young adults and to inform primary and secondary prevention measures in those with migraines," they concluded.

References:

1. Leppert MH, Poisson SH, Scarbro S, et al. Association of traditional and nontraditional risk factors in the development of strokes among young adults by sex and age group: a retrospective case-control study. Circ Cardiovasc Qual Outcomes. 2024;17:e010307. doi:10.1161/CIRCOUTCOMES.123.010307
2. Young adults with migraine, other nontraditional risk factors may have higher stroke risk. News release. American Heart Association. March 26, 2024. Accessed April 4, 2024. https://newsroom.heart.org/news/young-adults-with-migraine-other-nontraditional-risk-factors-may-have-higher-stroke-risk