Importance Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear. Objective To assess the association between long-term use of ADHD medication and the risk of CVD. Design, Setting, and Participants This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up. Exposure Cumulative duration of ADHD medication use up to 14 years. Main Outcomes and Measures The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs. Results Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged <25 years) and adults (aged ≥25 years). Conclusions and Relevance This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.

中文翻译：

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注意力缺陷/多动症药物和心血管疾病的长期风险。

重要性 过去几十年来，注意力缺陷/多动症 (ADHD) 药物的使用大幅增加。然而，与长期使用多动症药物相关的心血管疾病（CVD）的潜在风险仍不清楚。目的 评估长期使用 ADHD 药物与 CVD 风险之间的关联。设计、背景和参与者 这项病例对照研究包括瑞典年龄 6 至 64 岁的个人，他们在 2007 年 1 月 1 日至 2020 年 12 月 31 日期间接受过 ADHD 事件诊断或 ADHD 药物配发。有关 ADHD 和 CVD 诊断和治疗的数据ADHD 药物分配分别从瑞典国家住院患者登记处和瑞典处方药物登记处获得。病例包括患有注意力缺陷多动障碍（ADHD）和突发心血管疾病诊断（缺血性心脏病、脑血管疾病、高血压、心力衰竭、心律失常、血栓栓塞性疾病、动脉疾病和其他形式的心脏病）的个体。发病密度抽样用于根据年龄、性别和日历时间将病例与最多 5 名无 CVD 的对照进行匹配。病例和对照的随访时间相同。暴露 ADHD 药物使用累计持续时间长达 14 年。主要结果和措施 主要结果是CVD事件。CVD 与 ADHD 药物使用累积持续时间之间的关联是使用调整优势比 (AOR) 和 95% CI 来测量的。结果 在 278 027 名年龄 6 至 64 岁的 ADHD 患者中，确定了 10 388 名患有 CVD 的患者（中位 [IQR] 年龄，34.6 [20.0-45.7] 岁；6154 名男性 [59.2%]），并与 51 672 名无 CVD 的对照参与者进行匹配（中位 [IQR] 年龄为 34.6 [19.8-45.6] 岁；30 601 名男性 [59.2%]）。两组的中位随访时间 (IQR) 均为 4.1 (1.9-6.8) 年。与不使用相比，ADHD 药物使用累积持续时间较长与 CVD 风险增加相关（0 至 ≤1 年：AOR，0.99 [95% CI，0.93-1.06]；1 至 ≤2 年：AOR，1.09 [95% CI，1.01-1.18]；2 至≤3 年：AOR，1.15 [95% CI，1.05-1.25]；3 至≤5 年：AOR，1.27 [95% CI，1.17-1.39]；以及 >5 年： AOR，1.23 [95% CI，1.12-1.36]）。较长的累积 ADHD 药物使用时间与高血压风险增加相关（例如，3 至 ≤5 年：AOR，1.72 [95% CI，1.51-1.97] 和 > 5 年：AOR，1.80 [95% CI，1.55-2.08] ]）和动脉疾病（例如，3至≤5岁：AOR，1.65 [95% CI，1.11-2.45]和> 5岁：AOR，1.49 [95% CI，0.96-2.32]）。在 14 年的随访中，ADHD 药物使用量每增加 1 年，CVD 风险就会增加 4%（AOR，1.04 [95% CI，1.03-1.05]），其中 CVD 风险增加幅度更大。前 3 年的累积使用（AOR，1.08 [95% CI，1.04-1.11]）和剩余随访期间的稳定风险。在儿童和青少年（年龄<25 岁）以及成人（年龄≥25 岁）中也观察到类似的模式。结论和相关性 这项病例对照研究发现，长期接触 ADHD 药物与 CVD 风险增加相关，尤其是高血压和动脉疾病。这些发现强调了在做出有关长期使用多动症药物的治疗决策时仔细权衡潜在益处和风险的重要性。临床医生应在整个治疗过程中定期、持续地监测心血管体征和症状。