Am. J. Epidemiol：狼疮患者泼尼松用量应小于10mg/d

　　纽约——约翰霍普金斯大学的Michelle Petri博士在纽约大学主办的会议上报告称，泼尼松日剂量＞10 mg可使系统性红斑狼疮(SLE)患者的心血管事件(CVE)风险加倍。他建议，应尽最大努力确保红斑狼疮患者泼尼松用量<10 mg/d的临界值。

　　在这项旨在探索可能增加SLE患者CVE风险的因素的观察性队列研究中，研究者分析了霍普金斯狼疮队列中1,874例SLE患者的资料，该队列纳入了在23年期间(1987年4月~2010年6月)每季度在该中心就诊的患者。结果显示，在泼尼松用量为1~9 mg/d的患者中，共发生32例CVE，与普通人群预期发生率无显著差异。但10~19 mg/d患者的CVE风险显著增加[相对风险(RR)，2.4；P=0.002]，相当于20.2例/1,000(人·年)；用量≥20 mg/d的患者风险增加超过5倍(P＜0.001)，相当于35.4例/1,000(人·年)(Am. J. Epidemiol. 2012;176:708-19)。

　　校正年龄因素后，CVE发生率与病程无关，但与既往疾病平均活动度和目前抗双链DNA抗体水平存在关联。尽管既往累计用量≥36,500 mg(相当于10 mg/d泼尼松或类似药物使用≥10年)可使CVE发生率加倍(P=0.0066)，但过去服用而目前不使用糖皮质激素对CVE发生率没有影响。

　　研究者建议，为降低SLE患者的CVE风险，应对传统心血管风险因素(高血压、肥胖、高脂血症、吸烟和久坐生活方式)进行评估和控制。儿童和成人临床试验已表明，他汀类药物不能预防SLE患者动脉粥样硬化加速，小鼠实验也未见预防作用。吗替麦考酚酯(MMF)或许是一种潜在的治疗药物，但该药尚未被美国食品药品管理局(FDA)批准用于SLE治疗。尽管有一些证据显示MMF可减缓肾脏移植患者及小鼠动脉粥样硬化进程，但目前还没有临床研究支持该药物可用于SLE患者的治疗。Petri博士也不建议将MMF用于SLE患者，因为该药有一些警告信息(感染、淋巴瘤和恶性肿瘤、妊娠丢失和先天畸形、中性粒细胞减少症和红细胞发育不全、干扰口服避孕药等)。

　　研究者还指出，非甾体抗炎药物(NSAID)也与SLE患者心血管损伤风险增加66%相关，应避免使用类固醇和NSAID。上述结果也进一步凸显了对红斑狼疮新治疗药物的需求。

与系统性红斑狼疮相关的拓展阅读：

• PLoS ONE：左建平等青蒿素衍生物治疗系统性红斑狼疮研究再获进展
• 孙凌云:系统性红斑狼疮(SLE)药物治疗研究进展
• 回顾系统性红斑狼疮的十年研究进展
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Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus.
Abstract
Patients with systemic lupus erythematosus (SLE) are at excess risk of cardiovascular events (CVEs). There is uncertainty regarding the relative importance of SLE disease activity, medications, or traditional risk factors in this increased risk. To gain insight into this, the authors analyzed data from a cohort of 1,874 patients with SLE who were seen quarterly at a single clinical center (April 1987-June 2010) using pooled logistic regression analysis. In 9,485 person-years of follow-up, the authors observed 134 CVEs (rate = 14.1/1,000 person-years). This was 2.66 times what would be expected in the general population based on Framingham risk scores (95% confidence interval: 2.16, 3.16). After adjustment for age, CVE rates were not associated with duration of SLE. However, they were associated with average past levels of SLE disease activity and recent levels of circulating anti-double-stranded DNA. Past use of corticosteroids (in the absence of current use) was not associated with CVE rates. However, persons currently using 20 mg/day or more of corticosteroids had a substantial increase in risk even after adjustment for disease activity. Thus, consistent with findings in several recent publications among cohorts with other diseases, current use of corticosteroids was associated with an increased risk of CVEs. These results suggest a short-term impact of corticosteroids on CVE risk.