Neuro-Psychiatric Institute, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Department of Pharmacy, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Basic Clin Pharmacol Toxicol. 2018 Dec;123(6):756-765. doi: 10.1111/bcpt.13079. Epub 2018 Jul 31.
The prevalence of cardiovascular disease (CVD) is higher in patients with schizophrenia than in the general population. We aimed to investigate whether atypical antipsychotics (AAP) increase the levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), thereby increasing the risk of CVD. The data were from inpatients aged 18-60 years with a diagnosis of schizophrenia according to ICD-10 at the Affiliated Brain Hospital of Nanjing Medical University who underwent physical examination between 1 October 2014 and 30 September 2016. A retrospective cohort study was used to analyse the correlation between AAP, Lp-PLA2 levels and the CVD risk (it was determined that Lp-PLA2 values >200 ng/mL were defined as high CVD risk) in patients treated with monotherapy, olanzapine, clozapine or quetiapine. Data were collected for 452 patients with eligible schizophrenia: 163 treated with clozapine, 186 treated with olanzapine, 47 treated with quetiapine and 56 receiving no medication. Compared with the no-medication patients, AAP administration in patients with olanzapine, clozapine or quetiapine had higher serum Lp-PLA2 levels when age, sex, BMI and fasting glucose level were matched. AAP were significantly associated with serum Lp-PLA2 level by Spearman's correlation coefficients. The results of logistic regression analysis showed that AAP administration was an independent factor of CVD risk when adjusted by potential confounding factors. This study is the first to confirm that AAP administration, especially clozapine and olanzapine, could increase Lp-PLA2 levels and CVD risk, independent of drug-induced weight gain in schizophrenia. The extent and the factors of increasing Lp-PLA2 level and CVD risk in olanzapine, clozapine and quetiapine are discrepant. The possible effects of AAP on Lp-PLA2 in schizophrenia patients are involved in pro-inflammatory cytokines and hormones.
心血管疾病（CVD）在精神分裂症患者中的发病率高于普通人群。我们旨在研究非典型抗精神病药（AAP）是否会增加脂蛋白相关磷脂酶 A2（Lp-PLA2）的水平，从而增加 CVD 的风险。该数据来自于南京医科大学附属脑科医院符合国际疾病分类第 10 版（ICD-10）精神分裂症诊断标准的 18-60 岁住院患者，他们在 2014 年 10 月 1 日至 2016 年 9 月 30 日期间接受了体检。我们采用回顾性队列研究来分析 AAP、Lp-PLA2 水平与接受单一疗法、奥氮平、氯氮平和喹硫平治疗的患者 CVD 风险（确定 Lp-PLA2 值>200ng/ml 为高 CVD 风险）之间的相关性。共纳入了 452 例符合条件的精神分裂症患者：163 例服用氯氮平，186 例服用奥氮平，47 例服用喹硫平，56 例未服用药物。与未服用药物的患者相比，当年龄、性别、BMI 和空腹血糖水平匹配时，服用奥氮平、氯氮平或喹硫平的患者的血清 Lp-PLA2 水平更高。Spearman 相关系数显示 AAP 与血清 Lp-PLA2 水平显著相关。多因素逻辑回归分析结果显示，调整潜在混杂因素后，AAP 治疗是 CVD 风险的独立因素。这项研究首次证实，AAP 治疗，特别是氯氮平和奥氮平，可增加 Lp-PLA2 水平和 CVD 风险，与精神分裂症患者药物引起的体重增加无关。奥氮平、氯氮平和喹硫平增加 Lp-PLA2 水平和 CVD 风险的程度和因素不同。AAP 对精神分裂症患者 Lp-PLA2 的可能影响涉及促炎细胞因子和激素。
