Wiewel Maryse A, Scicluna Brendon P, van Vught Lonneke A, Hoogendijk Arie J, Zwinderman Aeilko H, Lutter René, Horn Janneke, Cremer Olaf L, Bonten Marc J, Schultz Marcus J, van der Poll Tom
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ, Amsterdam, The Netherlands.
The Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Ann Intensive Care. 2018 Jan 18;8(1):9. doi: 10.1186/s13613-017-0349-3.
Statins can exert pleiotropic anti-inflammatory, vascular protective and anticoagulant effects, which in theory could improve the dysregulated host response during sepsis. We aimed to determine the association between prior statin use and host response characteristics in critically ill patients with sepsis.
We performed a prospective observational study in 1060 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of these, 351 patients (33%) were on statin therapy before admission. The host response was evaluated by measuring 23 biomarkers providing insight into key pathways implicated in sepsis pathogenesis and by analyzing whole-blood leukocyte transcriptomes in samples obtained within 24 h after ICU admission. To account for indication bias, a propensity score-matched cohort was created (N = 194 in both groups for protein biomarkers and N = 95 in both groups for gene expression analysis).
Prior statin use was not associated with an altered mortality up to 90 days after admission (38.0 vs. 39.7% in the non-statin users in the propensity-matched analysis). Statin use did not modify systemic inflammatory responses, activation of the vascular endothelium or the coagulation system. The blood leukocyte genomic response, characterized by over-expression of genes involved in inflammatory and innate immune signaling pathways as well as under-expression of genes associated to T cell function, was not different between patients with and without prior statin use.
Statin therapy is not associated with a modified host response in sepsis patients on admission to the ICU.
他汀类药物可发挥多效抗炎、血管保护和抗凝作用，理论上可改善脓毒症期间失调的宿主反应。我们旨在确定脓毒症重症患者先前使用他汀类药物与宿主反应特征之间的关联。
2011年1月至2013年7月期间，我们对荷兰两家医院综合重症监护病房（ICU）收治的1060例脓毒症患者进行了一项前瞻性观察研究。其中，351例患者（33%）在入院前接受他汀类药物治疗。通过测量23种生物标志物评估宿主反应，这些生物标志物可深入了解脓毒症发病机制中的关键途径，并分析ICU入院后24小时内采集样本中的全血白细胞转录组。为了消除指征偏倚，创建了一个倾向评分匹配队列（蛋白质生物标志物两组各194例，基因表达分析两组各95例）。
入院后90天内，先前使用他汀类药物与死亡率改变无关（倾向匹配分析中，未使用他汀类药物的患者死亡率为38.0%，使用他汀类药物的患者死亡率为39.7%）。使用他汀类药物并未改变全身炎症反应、血管内皮激活或凝血系统。无论先前是否使用他汀类药物，患者血液白细胞基因组反应均无差异，其特征为参与炎症和固有免疫信号通路的基因过度表达以及与T细胞功能相关的基因表达不足。
入住ICU的脓毒症患者使用他汀类药物治疗与宿主反应改变无关。
