Li Mohan, Noordam Raymond, Trompet Stella, Winter Elizabeth M, Jukema J Wouter, Arbous M Sesmu, Rensen Patrick C N, Kooijman Sander
Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands (Drs Li, Winter, Jukema, Rensen, Kooijman); Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands (Drs Le, Winter, Rensen, Kooijman).
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands (Drs Noordam, Trompet).
J Clin Lipidol. 2024 Nov-Dec;18(6):e915-e925. doi: 10.1016/j.jacl.2024.07.006. Epub 2024 Jul 27.
Statins exert pleiotropic anti-inflammatory and antioxidant effects in addition to their cholesterol-lowering properties. This study aimed to investigate whether statin use is associated with improved outcomes of sepsis.
Data from patients with sepsis were extracted from the Medical Information Mart for Intensive Care IV database. Patients with a history of receiving prescriptions for statins (i.e., atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) were matched with non-users using propensity-score matching, to balance confounding factors between the groups. Mendelian randomization (MR) analyses were performed using information from the UK Biobank dataset to explore the potential causal link between low-density lipoprotein cholesterol (LDL-C) levels and LDL-C lowering effects via genetically inhibiting β‑hydroxy β-methylglutaryl-coenzyme A reductase and the susceptibility to sepsis, and the sepsis-related 28-day mortality.
90-day mortality rate was lower among the 10,323 statin users when compared to matched non-users [hazard ratio (HR): 0.612, 95% CI: 0.571 to 0.655]. In-hospital mortality was also lower for statin users compared to non-users (11.3% vs. 17.8%, p < 0.0001, HR: 0.590, 95% CI: 0.548 to 0.634). Statin use was associated with better outcome in all investigated subpopulations apart from patients with severe liver disease. MR analyses further pointed toward pleiotropic effects beyond lipid-lowering effects of statins on sepsis-related outcomes.
Statin use is associated with improved outcomes following sepsis-related intensive care unit (ICU) admission, most likely from its pleiotropic properties, characterized by lower 90-day and in-hospital mortality among statin users.
他汀类药物除了具有降低胆固醇的特性外，还具有多效性抗炎和抗氧化作用。本研究旨在调查使用他汀类药物是否与脓毒症预后改善相关。
从重症监护医学信息数据库IV中提取脓毒症患者的数据。使用倾向评分匹配将有他汀类药物（即阿托伐他汀、洛伐他汀、匹伐他汀、普伐他汀、瑞舒伐他汀或辛伐他汀）处方史的患者与未使用者进行匹配，以平衡组间混杂因素。利用英国生物银行数据集的信息进行孟德尔随机化（MR）分析，以探讨通过基因抑制β-羟基β-甲基戊二酰辅酶A还原酶降低低密度脂蛋白胆固醇（LDL-C）水平与LDL-C降低效应之间的潜在因果联系，以及脓毒症易感性和脓毒症相关的28天死亡率。
与匹配的未使用者相比，10323名他汀类药物使用者的90天死亡率较低[风险比（HR）：0.612，95%置信区间：0.571至0.655]。他汀类药物使用者的院内死亡率也低于未使用者（11.3%对17.8%，p<0.0001，HR：0.590，95%置信区间：0.548至0.634）。除重症肝病患者外，在所有调查的亚组中，使用他汀类药物均与更好的预后相关。MR分析进一步表明，他汀类药物除了降低血脂作用外，还对脓毒症相关结局具有多效性作用。
使用他汀类药物与脓毒症相关重症监护病房（ICU）入院后的预后改善相关，这很可能归因于其多效性特性，表现为他汀类药物使用者的90天和院内死亡率较低。
