Cardiovascular Safety of Stimulants in Children with Attention-Deficit/Hyperactivity Disorder: A Nationwide Prospective Cohort Study
Cardiovascular Safety of Stimulants in Children with Attention-Deficit/Hyperactivity Disorder: A Nationwide Prospective Cohort Study
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DOI：
10.1089/cap.2014.0020
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发表时间：
2014-08-01
影响因子：
1.9
通讯作者：
Simonsen, Marianne
中科院分区：
文献类型：
--
作者：
Dalsgaard, Soren;Kvist, Anette Primdal;Simonsen, Marianne
目的：本研究的目的是确定兴奋剂使用者是否比非使用者发生心血管事件的风险更高，在全国队列和基于人群的儿童和青少年诊断为注意力缺陷/多动障碍（ADHD）的样本中检查这种关联。我们还旨在研究一个可能的剂量反应关系，在这样的association.Methods：我们进行了一项纵向，前瞻性队列研究的所有儿童出生在丹麦之间的1990年和1999年。在这个队列中，确定了患有ADHD的儿童。使用唯一的个人身份证号码，合并了国家健康登记册中关于所有儿童及其父母的精神病和躯体疾病诊断、兴奋剂处方、心血管风险因素、产前和围产期以及社会人口协变量的数据。使用考克斯回归估计心血管事件的风险比（HR），调整其他已知的风险factors.Results：在总人口（n = 714，258贡献了6，767，982人年）使用兴奋剂增加心血管事件的风险，调整后的HR = 1.83（1.10-3.04）。ADHD患儿（n = 8300）兴奋剂治疗也增加了心血管事件的风险（校正的HR = 2.20 [2.15-2.24]），具有复杂的时间依赖性剂量反应关系。这是第一项关于儿童和青少年兴奋剂心血管安全性的全国性队列研究，据我们所知，这是最长的前瞻性随访研究。心血管事件是罕见的，但在兴奋剂使用者中的可能性是非使用者的两倍，无论是在全国总人口中还是在ADHD儿童中。我们发现儿童和青少年心血管不良事件与兴奋剂治疗之间存在复杂的、时间和剂量依赖性的相互关系。我们的研究结果表明，即使在调整了一些潜在的混杂因素后，儿童和青少年中与兴奋剂治疗相关的心血管疾病风险增加的安全性信号。
Objective: The purpose of this study was to determine whether stimulant users are at higher risk of a later cardiovascular event than are non-users, examining this association in both a national cohort and a population-based sample of children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). We also aim to examine a possible dose-response relationship in such an association.Methods: We conducted a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999. Within this cohort, children with ADHD were identified. Data from national health registers on psychiatric and somatic diagnoses, stimulant prescriptions, cardiovascular risk factors, pre- and perinatal and sociodemographic covariates in all children and their parents were merged, using the unique personal identification number. Hazard ratios (HR) for cardiovascular events were estimated using Cox regression, adjusted for other known risk factors.Results: In the total population (n = 714,258 contributing a total of 6,767,982 person-years) use of stimulants increased the risk of a cardiovascular event; adjusted HR = 1.83 (1.10-3.04). In children with ADHD (n = 8300) stimulant treatment also increased the risk of a cardiovascular event (adjusted HR = 2.20 [2.15-2.24]), with a complex time-dependent dose-response relationship.Conclusions: This is the first nationwide cohort study of the cardiovascular safety of stimulants in children and adolescents, and it represents, to our knowledge, the longest prospective follow-up study. Cardiovascular events were rare but twice as likely in stimulant users as in non-users, both in the total national population and in children with ADHD. We found a complex, time-and dose-dependent interrelationship between cardiovascular adverse events and stimulant treatment in children and adolescents. Our results suggest a safety signal with an increased risk of cardiovascular disease associated with stimulant treatment in children and adolescents, even after adjusting for a number of potential confounders.