Supplementary Material for: Risk factors for Stroke in the Young (18-45 Years); Case-control analysis of INTERSTROKE data from 32 countries

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 is 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 haemorrhage, 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% 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/Apo A1 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 (WHR) [OR 1·69 (95% CI 1·04-2·75)] were the most important risk factors for ischemic stroke in these young cases. For ICH, 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 Fraction (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, dyslipidaemia 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.

背景：目前尚不明确传统血管危险因素是否是45岁以下脑卒中患者多数发病的诱因。本研究旨在探讨45岁以下人群常见危险因素与脑卒中的关联。

方法：INTERSTROKE研究是一项于2007年至2015年间在32个国家开展的病例对照研究。纳入首次脑卒中（stroke）症状发作后5天内就诊的患者作为病例组；对照组与病例组年龄、性别相匹配，且无脑卒中病史。病例组与对照组接受相同的评估流程。本研究计算了比值比（Odds Ratio, OR）及人群归因危险度（Population-Attributable Risk, PAR），以明确45岁及以下患者各类危险因素与总脑卒中、缺血性脑卒中（ischemic stroke）及颅内出血（intracranial haemorrhage）的关联。

研究结果：本分析共纳入1582对病例对照。该队列的平均年龄为38.5岁（标准差SD 6.32）。总体而言，71%的脑卒中为缺血性脑卒中。针对该年轻病例组，缺血性脑卒中的重要危险因素包括心脏病因[OR 8.42（95%置信区间CI 3.01-23.5）]、过量饮酒[OR 5.44（95%CI 1.81-16.4）]、高血压[OR 5.41（95%CI 3.40-8.58）]、载脂蛋白B/载脂蛋白A1比值[ApoB/ApoA1比值，OR 2.74（95%CI 1.69-4.46）]、社会心理压力[OR 2.33（95%CI 1.01-5.41）]、吸烟[OR 1.85（95%CI 1.17-2.94）]及腰围臀围比（Waist-to-Hip Ratio, WHR）升高[OR 1.69（95%CI 1.04-2.75）]。针对颅内出血（ICH），仅高血压[OR 9.08（95%CI 5.46-15.1）]与过量饮酒[OR 4.06（95%CI 1.27-13.0）]为显著危险因素。关联强度及人群归因分值（Population Attributable Fraction, PAF）随年龄增长而升高：<35岁人群的PAF为23.3%，35-45岁人群的PAF为50.7%。

解读：高血压、吸烟、过量饮酒、中心性肥胖、心脏病因、血脂异常及社会心理压力等传统危险因素，是45岁以下人群脑卒中的重要致病因素。高血压是所有年龄组、各地区及两种脑卒中亚型中最显著的危险因素。应在成年早期识别并干预此类危险因素，以预防年轻人群发生脑卒中。