Background: It is not clear whether conventional vascular risk factors are responsible for most strokes in patients younger than 45 years of age. Our objective was to evaluate the association of common risk factors with stroke in individuals under 45 years. Methods: INTERSTROKE was a case-control study carried out in 32 countries between 2007 and 2015. Patients presenting within 5 days of symptom onset of a first stroke were enrolled as cases. Controls were age and sex matched to cases and had no history of stroke. Cases and controls underwent similar evaluations. Odds ratios (ORs) and population attributable risks (PARs) were calculated to determine the association of various risk factors with all stroke, ischemic stroke, and intracranial hemorrhage, for patients 45 years of age or younger. Findings: 1,582 case-control pairs were included in this analysis. The mean age of this cohort was 38.5 years (SD 6.32). Overall, 71% strokes were ischemic. Cardiac causes {OR: 8.42 (95% confidence interval [CI]: 3.01–23.5)}; binge drinking of alcohol (OR: 5.44 [95% CI: 1.81–16.4]); hypertension (OR: 5.41 [95% CI: 3.40–8.58]); ApoB/ApoA1 ratio (OR: 2.74 [95% CI: 1.69–4.46]); psychosocial stress (OR: 2.33 [95% CI: 1.01–5.41]); smoking (OR: 1.85 [95% CI: 1.17–2.94]); and increased waist-to-hip ratio (OR: 1.69 [95% CI: 1.04–2.75]) were the most important risk factors for ischemic stroke in these young cases. For intracerebral hemorrhage, only hypertension (OR: 9.08 [95% CI: 5.46–15.1]) and binge drinking (OR: 4.06 [95% CI: 1.27–13.0]) were significant risk factors. The strength of association and population attributable risk (PAR) for hypertension increased with age (PAR 23.3% in those <35 years of age, 50.7% in 35–45 years of age). Interpretation: Conventional risk factors such as hypertension, smoking, binge drinking of alcohol, central obesity, cardiac causes, dyslipidemia, and psychosocial stress are important risk factors for stroke in those younger than 45 years of age. Hypertension is the most significant risk factor in all age groups and across all regions and both stroke subtypes. These risk factors should be identified and modified in early adulthood to prevent strokes in young individuals.

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