Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate headache and outcome in patients with acute stroke. Materials and methods Patients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the efficacy of nitric oxide in stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give OR and mean difference (MD) with 95% CI. Results In 4011 patients, headache was more common in GTN than control (360, 18.0% vs 170, 8.5%; p<0.001). Nitrate-related headache was associated with: younger age, female sex, higher diastolic blood pressure, non-total anterior circulation syndrome, milder stroke and absence of dysphasia (p<0.05). Nitrate headache was not associated with improved functional outcome (OR 0.90, 95% CI 0.73 to 1.10, p=0.30) or death (day 90) (HR 0.64, 95% CI 0.40 to 1.02, p=0.062), but reduced death or deterioration (day 7) (OR 0.45, 95% CI 0.25 to 0.82), death in hospital (OR 0.44, 95% CI 0.22 to 0.88) and improved activities of daily living (Barthel index, MD 3.7, 95% CI 0.3 to 7.1) and cognition (telephone interview cognitive screen, MD 2.0, 95% CI 0.7 to 3.3) (day 90). Non-nitrate headache was not associated with death, disability or cognition. Discussion and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90, which was not seen with non-nitrate headache. Data are available on reasonable request. Individual participant data will be shared with the Virtual International Stroke Trials Archive (VISTA) collaboration. From 1 January 2022, the chief investigator and trial steering committee will consider other requests to share individual participant data via email at: enos@nottingham.ac.uk. We will require a protocol detailing hypothesis, aims, analyses and intended tables and figures. Where possible, we will perform the analyses; if not, deidentified data and a data dictionary will be supplied for the necessary variables for remote analysis. Any sharing will be subject to a signed data access agreement. Ultimately, the data will be published.

中文翻译：

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急性卒中患者硝酸盐类头痛与预后的关系：一氧化氮在卒中 (ENOS) 试验中的疗效结果

简介 硝酸盐引起的头痛很常见，可能表明脑血管系统反应灵敏。我们评估了急性卒中患者硝酸盐类头痛与预后之间的关系。材料和方法 在中风试验中一氧化氮的疗效中，患者被随机分配到三硝酸甘油酯 (GTN) 组与无 GTN 组。评估了治疗结束时（第 7 天）头痛的发展，以及第 90 天时的功能结果（改良的 Rankin 量表，主要结果）。分析针对基线预后因素进行了调整，并给出了具有 95% CI 的 OR 和平均差 (MD)。结果 在 4011 名患者中，GTN 患者的头痛比对照组更常见（360, 18.0% vs 170, 8.5%；p<0.001）。硝酸盐相关性头痛与以下因素相关：年龄较小、女性、舒张压升高、非全前循环综合征、中风较轻且无言语障碍（p<0.05）。硝酸盐类头痛与改善功能结果（OR 0.90，95% CI 0.73 至 1.10，p=0.30）或死亡（第 90 天）（HR 0.64，95% CI 0.40 至 1.02，p=0.062）无关，但减少死亡或恶化（第 7 天）（OR 0.45，95% CI 0.25 至 0.82），住院死亡（OR 0.44，95% CI 0.22 至 0.88）和日常生活活动改善（Barthel 指数，MD 3.7，95% CI 0.3 至 7.1 ）和认知（电话采访认知屏幕，MD 2.0，95% CI 0.7 至 3.3）（第 90 天）。非硝酸盐性头痛与死亡、残疾或认知无关。讨论和结论 卒中后第 7 天出现硝酸盐类头痛可能与第 90 天日常生活活动的改善和认知障碍有关，而非硝酸盐类头痛则没有。可根据合理要求提供数据。个人参与者数据将与虚拟国际中风试验档案 (VISTA) 合作共享。从 2022 年 1 月 1 日起，首席研究员和试验指导委员会将考虑通过电子邮件共享个人参与者数据的其他请求：enos@nottingham.ac.uk。我们将需要一份详细说明假设、目标、分析和预期表格和数字的协议。在可能的情况下，我们将进行分析；如果没有，将为远程分析所需的变量提供去识别的数据和数据字典。任何共享都将受到签署的数据访问协议的约束。最终，数据将被发布。首席研究员和试验指导委员会将考虑通过电子邮件共享个人参与者数据的其他请求：enos@nottingham.ac.uk。我们将需要一份详细说明假设、目标、分析和预期表格和数字的协议。在可能的情况下，我们将进行分析；如果没有，将为远程分析所需的变量提供去识别的数据和数据字典。任何共享都将受到签署的数据访问协议的约束。最终，数据将被发布。首席研究员和试验指导委员会将考虑通过电子邮件共享个人参与者数据的其他请求：enos@nottingham.ac.uk。我们将需要一份详细说明假设、目标、分析和预期表格和数字的协议。在可能的情况下，我们将进行分析；如果没有，将为远程分析所需的变量提供去识别的数据和数据字典。任何共享都将受到签署的数据访问协议的约束。最终，数据将被发布。任何共享都将受到签署的数据访问协议的约束。最终，数据将被发布。任何共享都将受到签署的数据访问协议的约束。最终，数据将被发布。