Division of Rheumatology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK.
Lupus Sci Med. 2023 Jul;10(2). doi: 10.1136/lupus-2023-000923.
Cognitive dysfunction (CD) is detectable in approximately 40% of patients with SLE. Despite this high prevalence, there are no approved pharmacological treatment options for this detrimental condition. Preliminary murine studies show potential for targeting microglial activation as a treatment of SLE-CD, which may be ameliorated with centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use. The aim of this study is to determine if there is an association of cACEi/cARB use with cognitive function in a human SLE cohort.
The American College of Rheumatology neuropsychological battery was administered to patients with consecutive SLE at a single academic health centre at baseline, 6 and 12 months. Scores were compared with sex-matched and age-matched control subjects. Clinical and demographic data were gathered at each visit. The primary outcome was CD defined as dysfunction in two or more cognitive domains. The primary predictor was a total cumulative dose of cACEi/cARB in milligrams per kilogram, recorded as an equivalent ramipril dose. Odds of CD with respect to cACEi/cARB use were determined through generalised linear mixed modelling.
A total of 300 patients, representing 676 visits, completed this study. One hundred sixteen (39%) met the criteria for CD. Fifty-three participants (18%) were treated with a cACEi or cARB. Mean cumulative dose was 236 mg/kg (calculated as equivalent ramipril dose). Cumulative cACEi/cARB dose was not protective against SLE-CD. Caucasian ethnicity, current employment status and azathioprine cumulative dose were each associated with reduced odds of SLE-CD. Increasing Fatigue Severity Scale score was associated with increased odds of CD.
In a single-centre SLE cohort, cACEi/cARB use was not associated with absence of CD. Many important confounders may have influenced the results of this retrospective study. A randomised trial is required to accurately determine if cACEi/cARB is a potential treatment for SLE-CD.
认知功能障碍（CD）在大约 40%的系统性红斑狼疮（SLE）患者中可被检测到。尽管这种患病率很高，但针对这种有害情况尚无批准的药物治疗选择。初步的小鼠研究表明，靶向小胶质细胞激活可能是治疗 SLE-CD 的一种方法，使用中枢作用的血管紧张素转换酶抑制剂（cACEi）和血管紧张素受体阻滞剂（cARB）可能会改善这种情况。本研究旨在确定在人类 SLE 队列中，使用 cACEi/cARB 是否与认知功能有关。
在单一学术医疗中心，对连续就诊的 SLE 患者在基线、6 个月和 12 个月时进行美国风湿病学会神经心理测试包测试。将分数与性别匹配和年龄匹配的对照组进行比较。每次就诊时收集临床和人口统计学数据。主要结局是 CD，定义为两个或更多认知领域的功能障碍。主要预测因子是每千克毫克数的 cACEi/cARB 总累积剂量，以等效雷米普利剂量记录。使用广义线性混合模型确定 cACEi/cARB 使用与 CD 的比值比。
共有 300 名患者，代表 676 次就诊，完成了这项研究。116 名（39%）符合 CD 标准。53 名参与者（18%）接受了 cACEi 或 cARB 治疗。平均累积剂量为 236mg/kg（以等效雷米普利剂量计算）。累积 cACEi/cARB 剂量并不能预防 SLE-CD。白种人种族、当前就业状况和硫唑嘌呤累积剂量与 SLE-CD 减少的几率相关。疲劳严重程度量表评分的增加与 CD 的几率增加相关。
在单中心 SLE 队列中，cACEi/cARB 的使用与 CD 的缺失无关。许多重要的混杂因素可能影响了这项回顾性研究的结果。需要进行随机试验以准确确定 cACEi/cARB 是否是 SLE-CD 的潜在治疗方法。
