基于影像学的风险评分在缺血性卒中或短暂性脑缺血发作后接受抗栓治疗患者颅内出血和缺血性卒中预测中的开发：来自队列研究的个体患者数据汇总分析
Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.
作者信息
Best Jonathan G, Ambler Gareth, Wilson Duncan, Lee Keon-Joo, Lim Jae-Sung, Shiozawa Masayuki, Koga Masatoshi, Li Linxin, Lovelock Caroline, Chabriat Hugues, Hennerici Michael, Wong Yuen Kwun, Mak Henry Ka Fung, Prats-Sanchez Luis, Martínez-Domeño Alejandro, Inamura Shigeru, Yoshifuji Kazuhisa, Arsava Ethem Murat, Horstmann Solveig, Purrucker Jan, Lam Bonnie Yin Ka, Wong Adrian, Kim Young Dae, Song Tae-Jin, Lemmens Robin, Eppinger Sebastian, Gattringer Thomas, Uysal Ender, Tanriverdi Zeynep, Bornstein Natan M, Ben Assayag Einor, Hallevi Hen, Molad Jeremy, Nishihara Masashi, Tanaka Jun, Coutts Shelagh B, Polymeris Alexandros, Wagner Benjamin, Seiffge David J, Lyrer Philippe, Algra Ale, Kappelle L Jaap, Al-Shahi Salman Rustam, Jäger Hans R, Lip Gregory Y H, Fischer Urs, El-Koussy Marwan, Mas Jean-Louis, Legrand Laurence, Karayiannis Christopher, Phan Thanh, Gunkel Sarah, Christ Nicolas, Abrigo Jill, Leung Thomas, Chu Winnie, Chappell Francesca, Makin Stephen, Hayden Derek, Williams David J, Mess Werner H, Nederkoorn Paul J, Barbato Carmen, Browning Simone, Wiegertjes Kim, Tuladhar Anil M, Maaijwee Noortje, Guevarra Anne Cristine, Yatawara Chathuri, Mendyk Anne-Marie, Delmaire Christine, Köhler Sebastian, van Oostenbrugge Robert, Zhou Ying, Xu Chao, Hilal Saima, Gyanwali Bibek, Chen Christopher, Lou Min, Staals Julie, Bordet Régis, Kandiah Nagaendran, de Leeuw Frank-Erik, Simister Robert, Hendrikse Jeroen, Kelly Peter J, Wardlaw Joanna, Soo Yannie, Fluri Felix, Srikanth Velandai, Calvet David, Jung Simon, Kwa Vincent I H, Engelter Stefan T, Peters Nils, Smith Eric E, Hara Hideo, Yakushiji Yusuke, Orken Dilek Necioglu, Fazekas Franz, Thijs Vincent, Heo Ji Hoe, Mok Vincent, Veltkamp Roland, Ay Hakan, Imaizumi Toshio, Gomez-Anson Beatriz, Lau Kui Kai, Jouvent Eric, Rothwell Peter M, Toyoda Kazunori, Bae Hee-Joon, Marti-Fabregas Joan, Werring David J
机构信息
UCL Stroke Research Centre, Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, London, UK.
Department of Statistical Science, University College London, Gower Street, London, UK.
出版信息
Lancet Neurol. 2021 Apr;20(4):294-303. doi: 10.1016/S1474-4422(21)00024-7. Epub 2021 Mar 17.
BACKGROUND
Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk.
METHODS
We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602.
FINDINGS
The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models.
INTERPRETATION
The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted.
FUNDING
British Heart Foundation and Stroke Association.
背景
对于缺血性卒中或短暂性脑缺血发作后接受抗栓治疗的患者，平衡复发性缺血性卒中和颅内出血的风险至关重要。然而，现有的预测模型性能不足，尤其是在评估颅内出血风险方面。我们旨在开发新的风险评分，纳入临床变量和脑微出血，脑微出血是颅内出血和缺血性卒中风险的一种磁共振成像生物标志物。
方法
我们对来自国际脑微出血协作网络（MICON）的个体患者数据进行了汇总分析，该网络包括来自18个国家的38项基于医院的前瞻性队列研究。所有研究均招募有既往缺血性卒中或短暂性脑缺血发作的参与者，获取基线磁共振成像以量化脑微出血，并对参与者进行缺血性卒中和颅内出血的随访。排除未服用抗栓药物的参与者。我们开发了Cox回归模型来预测颅内出血和缺血性卒中的5年风险，根据生物学相关性选择候选预测因素，并使用向后剔除法简化模型。我们得出整数风险评分以供临床使用。我们在内部验证中评估模型性能，并使用自抽样法对乐观偏差进行校正。该研究已在PROSPERO注册，注册号为CRD42016036602。
结果
纳入的研究在2001年8月28日至2018年2月4日期间招募参与者。15766名参与者接受了颅内出血随访，15784名参与者接受了缺血性卒中随访。在中位随访2年期间，报告了184例颅内出血和1048例缺血性卒中。我们开发的风险模型包括脑微出血负担和简单的临床变量。颅内出血模型经乐观偏差校正后的c指数为0.73（95%CI 0.69 - 0.77），校准斜率为
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