Importance: Arterial ischemic stroke (AIS) incidence has decreased overall in recent decades yet has increased in young adults. The potential associations with atherosclerotic risk factors (ARFs) remain unknown.
Objective: To assess the ages at which ARFs may be risk factors associated with AIS.
Design, setting, and participants: A nested case-control study was conducted within Kaiser Permanente Northern California (KPNC) from January 1, 2000, through December 31, 2014. Data were analyzed from 2019 to 2022. Cases were identified using diagnostic codes and radiology reports. A total of 2 to 3 controls per case, matched on age and enrollment dates, were randomly identified and confirmed as stroke-free by medical record review. Only ARFs documented prior to stroke diagnosis (or the same date in controls) were considered to ensure the same period of observation. Comparisons were stratified by decade of life. Cases and controls were selected from the KPNC population (4.7 million children and 7.5 million young adults). Medical record review was conducted of all children (aged 29 days to 19 years) and a sample of young adults (aged 20-49 years) with International Classification of Diseases, Ninth Revision code or radiology text string search suggestive of AIS. Stroke-free controls were randomly selected.
Exposures: Hypertension, hyperlipidemia, diabetes, obesity, and smoking history.
Main outcomes and measures: Odds of AIS. In all analyses, cases and controls were compared using logistic regression.
Results: A total of 141 pediatric cases (69 [48.9%] aged 29 days to 9 years; 72 [51.1%] aged 10-19 years) and 364 pediatric controls (168 [46.2%] aged 0-9 years; 196 [53.8%] aged 10-19 years) and 455 young adult cases (71 [15.6%] aged 20-29 years; 144 [31.6%] aged 30-39 years; and 240 [52.7%] aged 40-49 years) and 1018 young adult controls (121 [11.9%] aged 20-29 years; 298 [29.3%] aged 30-39 years; and 599 [58.8%] aged 40-49 years) were identified. The percent of the cases that were male or female did not differ from the percent in the control group. The odds ratio (OR) of having any ARFs on AIS was 1.87 (95% CI, 0.72-4.88) for age range 0 to 9 years; OR, 1.00 (95% CI, 0.51-1.99) for age range 10 to 19 years; OR, 2.3 (95% CI, 1.17- 4.51) for age range 20 to 29 years; OR, 3.57 (95% CI, 2.34-5.45) for age range 30 to 39 years; and OR, 4.91 (95% CI, 3.52-6.86) for age range 40 to 49 years. The risk associated with multiple ARFs was OR, 5.29 (95% CI, 0.47-59.4) for age range 0 to 9 years; OR, 2.75 (95% CI, 0.77-9.87) for age range 10 to 19 years; OR, 7.33 (95% CI, 1.92-27.9) for age range 20 to 29 years; OR, 9.86 (95% CI, 4.96-19.6) for age range 30 to 39 years; and OR, 9.35 (95% CI, 6.31-13.8) for age range 40 to 49 years. The ARF findings by both definitions were significant in all young adult groups. Atherosclerosis was the presumed etiology in 0% of cases in the age group 0 to 9 years, 1.4% in the age group 10 to 19 years, 8.5% in the age group 20 to 29 years, 21.5% in the age group 30 to 39 years, and 42.5% in the age group 40 to 49 years.
Conclusions and relevance: Although atherosclerosis may not be a common cause of AIS in children or in early young adulthood, findings of this study suggest that ARFs associated with stroke in older adults are present in childhood and increase with age. Efforts to reduce these risk factors should begin as early as possible.