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. 2024 Apr;17(4):e010307.
doi: 10.1161/CIRCOUTCOMES.123.010307. Epub 2024 Mar 26.

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

Michelle H Leppert  1   2   3 , Sharon N Poisson  1 , Sharon Scarbro  2   4 , Krithika Suresh  5 , Lynda D Lisabeth  5 , Jukka Putaala  6 , Lee H Schwamm  7 , Stacie L Daugherty  3   8   9 , Cathy J Bradley  10 , James F Burke  11 , P Michael Ho  3   9   12
Affiliations

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

Michelle H Leppert et al. Circ Cardiovasc Qual Outcomes. 2024 Apr.

Abstract

Background: Despite women having fewer traditional risk factors (eg, hypertension, diabetes), strokes are more common in women than men aged ≤45 years. This study examined the contributions of traditional and nontraditional risk factors (eg, migraine, thrombophilia) in the development of strokes among young adults.

Methods: This retrospective case-control study used Colorado's All Payer Claims Database (2012-2019). We identified index stroke events in young adults (aged 18-55 years), matched 1:3 to stroke-free controls, by (1) sex, (2) age±2 years, (3) insurance type, and (4) prestroke period. All traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date (defined as the prestroke period). Conditional logistic regression models stratified by sex and age group first assessed the association of stroke with counts of risk factors by type and then computed their individual and aggregated population attributable risks.

Results: We included 2618 cases (52% women; 73.3% ischemic strokes) and 7827 controls. Each additional traditional and nontraditional risk factors were associated with an increased risk of stroke in all sex and age groups. In adults aged 18 to 34 years, more strokes were associated with nontraditional (population attributable risk: 31.4% men and 42.7% women) than traditional risk factors (25.3% men and 33.3% women). The contribution of nontraditional risk factors declined with age (19.4% men and 27.9% women aged 45-55 years). The contribution of traditional risk factors peaked among patients aged 35 to 44 years (32.8% men and 39.7% women). Hypertension was the most important traditional risk factor and increased in contribution with age (population attributable risk: 27.8% men and 26.7% women aged 45 to 55 years). Migraine was the most important nontraditional risk factor and decreased in contribution with age (population attributable risk: 20.1% men and 34.5% women aged 18-35 years).

Conclusions: Nontraditional risk factors were as important as traditional risk factors in the development of strokes for both young men and women and have a stronger association with the development of strokes in adults younger than 35 years of age.

Keywords: coronary disease; epidemiology; sex characteristics; stroke; young adult.

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Conflict of interest statement

Disclosures Dr Leppert was supported by the American Heart Association Career Development Award. Dr Putaala has taken part in stroke studies: TASTE (Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial), TEMPO-2 (A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion), and TWIST (Tenecteplase in Wake-Up Ischaemic Stroke Trial). Dr Schwamm reported serving on the American Heart Association/Get With The Guidelines stroke systems of care advisory group and the American Stroke Association Advisory Committee; stroke systems consultant to the Massachusetts Department of Public Health; scientific consultant regarding trial design and conduct to Genentech (late window thrombolysis, a member of steering committee TIMELESS [Tenecteplase in Stroke Patients Between 4.5 and 24 Hours; NCT03785678]); a member of a Data Safety Monitoring Board for Penumbra (MIND: Artemis in the Removal of Intracerebral Hemorrhage; NCT03342664); Diffusion Pharma (PHAST-TSC [Efficacy and Safety of Trans Sodium Crocetinate for Treatment of Suspected Stroke; NCT03763929]); a national principal investigator (PI) or a member of the National Steering Committee for Medtronic (Stroke AF [Rate of Atrial Fibrillation Through 12 Months in Patients With Recent Ischemic Stroke of Presumed Known Origin; NCT02700945]); a PI of the StrokeNet Network National Institute of Neurological Disorders and Stroke (NINDS; New England Regional Coordinating Center; U24NS107243); and a co-investigator of The Impact of Telestroke on Patterns of Care and Long-Term Outcomes, NINDS (R01NS111952). Dr Burke reports compensation from the American Heart Association for other services; he also serves as an associate editor for Circulation: Cardiovascular Quality and Outcomes. Dr Ho was supported by the National Heart, Lung, and Blood Institute, Veteran’s Affairs Health Services and Development, and the University of Colorado School of Medicine. Dr Ho has a research agreement with Bristol-Myers Squibb through the University of Colorado. Dr Ho serves as the Deputy Editor of Circulation: Cardiovascular Quality and Outcomes. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Eligibility and Inclusion Flowchart from the Colorado All Payer Claims dataset, for young adults between 18–55 years old from January 1st, 2012 until April 30th, 2019.
Figure 2:
Figure 2:
Odds ratio of the association of each additional risk factor compared to none (reference) with the development of strokes in A, Men and B, Women by age group.
Figure 3.
Figure 3.
Population attributable risk (PAR) of traditional vascular and non-traditional risk factors with top three contributing individual risk factors in A, Men and B, Women by age group. * denotes p<0.05 by age group. Dis- Disease.
Figure 4.
Figure 4.
Why do migraines lead to strokes? Categories of Etiological Contributions (ovals) and specific mechanisms leading to stroke in migraineurs. CADASIL- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, MTHFR-methylenetetrahydrofolate reductase, NSAIDs- Non-steroidal anti-inflammatory drugs.
See this image and copyright information in PMC

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