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Abstract：
BACKGROUND: The association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics.
METHODS: Adults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia.
RESULTS: 5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99-1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78-1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71-1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05-1.43]).
CONCLUSIONS: The risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.
METHODS: Adults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia.
RESULTS: 5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99-1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78-1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71-1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05-1.43]).
CONCLUSIONS: The risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.
摘要：
背景：抗高血压药物与精神分裂症之间的关联越来越受到关注；然而，基于大规模观察性研究的抗高血压药物对后续精神分裂症影响的证据有限.我们旨在比较使用血管紧张素转换酶（ACE）抑制剂与使用血管紧张素受体阻滞剂（ARB）或噻嗪类利尿剂的基于美国和韩国的大型高血压患者队列中精神分裂症的风险。
方法：初诊为高血压并接受ACE抑制剂治疗的18岁成年人，ARBs,包括或噻嗪类利尿剂作为一线抗高血压药物。研究人群基于年龄(>45岁)进行分组。使用大规模倾向评分（PS）匹配算法对对照组进行匹配。主要终点是精神分裂症的发病率。
结果：5,907,522;2,923,423;1,971,549名患者使用了ACE抑制剂，ARBs,噻嗪类利尿剂,分别。PS匹配后，精神分裂症的风险在各组之间没有显着差异(ACE抑制剂与ARB：汇总危险比[HR]1.15[95%置信区间，CI，0.99-1.33]；ACE抑制剂与噻嗪类利尿剂：汇总HR0.91[95%CI，0.78-1.07]）。在较旧的亚组中，ACE抑制剂和噻嗪类利尿剂之间没有显着差异（总结HR，0.91[95%CI，0.71-1.16]）。ACE抑制剂组的精神分裂症风险明显高于ARB组（总结HR，1.23[95%CI，1.05-1.43]）。
结论：ACE抑制剂与ACE抑制剂之间的精神分裂症风险没有显着差异ARB和ACE抑制剂与噻嗪类利尿剂组。需要进一步的调查来确定与抗高血压药物相关的精神分裂症的风险，尤其是年龄>45岁的人群。
方法：初诊为高血压并接受ACE抑制剂治疗的18岁成年人，ARBs,包括或噻嗪类利尿剂作为一线抗高血压药物。研究人群基于年龄(>45岁)进行分组。使用大规模倾向评分（PS）匹配算法对对照组进行匹配。主要终点是精神分裂症的发病率。
结果：5,907,522;2,923,423;1,971,549名患者使用了ACE抑制剂，ARBs,噻嗪类利尿剂,分别。PS匹配后，精神分裂症的风险在各组之间没有显着差异(ACE抑制剂与ARB：汇总危险比[HR]1.15[95%置信区间，CI，0.99-1.33]；ACE抑制剂与噻嗪类利尿剂：汇总HR0.91[95%CI，0.78-1.07]）。在较旧的亚组中，ACE抑制剂和噻嗪类利尿剂之间没有显着差异（总结HR，0.91[95%CI，0.71-1.16]）。ACE抑制剂组的精神分裂症风险明显高于ARB组（总结HR，1.23[95%CI，1.05-1.43]）。
结论：ACE抑制剂与ACE抑制剂之间的精神分裂症风险没有显着差异ARB和ACE抑制剂与噻嗪类利尿剂组。需要进一步的调查来确定与抗高血压药物相关的精神分裂症的风险，尤其是年龄>45岁的人群。
