The neutrophil-lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials
The neutrophil-lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials
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DOI：
10.1093/eurheartj/ehaa1034
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发表时间：
2021-01-08
影响因子：
39.3
通讯作者：
Ridker, Paul M.
中科院分区：
文献类型：
--
作者：
Adamstein, Nicholas H.;MacFadyen, Jean G.;Ridker, Paul M.
嗜中性粒细胞-淋巴细胞比率（NLR）是一种容易获得的炎症生物标志物，可能与动脉粥样硬化相关并预测心血管（CV）事件。本研究的目的是确定NLR是否可预测主要不良心血管事件（MACE）的发生，并通过抗炎治疗进行调整。方法和结果根据CANTOS、JUPITER、SPIRE-1、SPIRE-2和CIRT试验中随机接受安慰剂或卡那单抗、瑞舒伐他汀、bococizumab或甲氨蝶呤的60087名参与者的全血细胞计数计算基线和治疗中NLR，并随访MACE。所有分析首先在CANTOS中进行，然后在其他四项试验中进行外部验证。对于这5项试验，使用考克斯比例风险模型计算比较NLR四分位数的主要CV事件和死亡率的风险比，并评价每种随机化干预与安慰剂相比对NLR的影响。NLR与白细胞介素-6、C反应蛋白和纤维蛋白原水平适度相关，但与脂质的相关性最低。在所有5项随机试验中，基线NLR可预测CV事件和死亡; CANTOS中MACE风险的每四分位数增加为20%[95%置信区间（CI）14- 25%，P < 0.0001]，SPIRE-1中为31%（95% CI 14- 49%，P = 0.00007），SPIRE-2为27%（95% CI 12- 43%，P = 0.0002），CIRT为9%（95% CI 0.2- 20%，P = 0.045），JUPITER为11%（95% CI 122%，P = 0.03）。虽然降脂药物对NLR没有显著影响，但使用canakinumab的抗炎治疗降低了NLR（P < 0.0001）。结论NLR是一种容易获得的炎症生物标志物，可独立预测CV风险和全因死亡率，并且可通过使用canakinumab阻断白细胞介素-1b而降低。
Aims The neutrophil-lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapyMethods and results Baseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14-49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12-43%, P = 0.0002), 9% in CIRT (95% CI 0.2-20%, P = 0.045), and 11% in JUPITER (95% CI 122%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001)Conclusion The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1b blockade with canakinumab.