Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
JAMA Cardiol. 2021 Dec 1;6(12):1440-1445. doi: 10.1001/jamacardio.2021.3079.
Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease.
To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020.
Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs ≥2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [≥90 mL/min/1.73 m2], mildly decreased eGFR level [60-90 mL/min/1.73 m2], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m2]).
Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke.
This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (≥2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]).
In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.
炎症可促进心血管疾病的发生，而抗炎治疗可降低慢性冠状动脉综合征患者的心血管事件发生率。慢性肾脏病（CKD）是心血管疾病的一个危险因素。目前尚不清楚 CKD 患者中白细胞介素 6（IL-6）介导的炎症与心血管疾病之间的关系。
研究与肾功能相关的慢性冠状动脉综合征患者中 IL-6 与心血管结局之间的关系。
设计、地点和参与者：这是一项多中心队列研究，纳入了在 39 个国家的 663 个中心参加慢性冠状动脉综合征稳定性斑块启动达拉普利治疗试验（STABILITY）的患者。患者于 2008 年 12 月至 2010 年 4 月入组，中位随访时间为 3.7 年。这项子研究的分析于 2020 年 9 月开始。
暴露因素为基线时收集的 IL-6 和肌酐估计肾小球滤过率（eGFR）。连续和分类水平（<2.0 ng/L 与≥2.0 ng/L）的 IL-6 与心血管结局之间的关系，与 eGFR 临界值（正常 eGFR 水平[≥90 mL/min/1.73 m2]、轻度降低 eGFR 水平[60-90 mL/min/1.73 m2]和中度至重度降低 eGFR 水平[<60 mL/min/1.73 m2]）进行了检验。
主要结局为主要不良心血管事件（MACE），包括心血管死亡、心肌梗死和卒中的复合终点。
这项 STABILITY 试验的子研究纳入了 14611 例基线时可获得 IL-6 水平的患者。中位（四分位距）年龄为 65（59-71）岁，2700 例（18.5%）为女性。随访期间，1459 例（10.0%）发生 MACE。在所有 CKD 分层中，较高水平的 IL-6 在连续模型中独立与 MACE 风险相关（P < .001）。在预先设定的分层中，升高的 IL-6 水平（≥2.0 vs <2.0 ng/L）与正常肾功能（2.9% vs 1.9%事件/年[危险比，1.35；95%CI，1.02-1.78]）、轻度 CKD（3.3% vs 1.9%[危险比，1.57；95%CI，1.35-1.83]）和中重度 CKD（5.0% vs 2.9%[危险比，1.60；95%CI，1.28-1.99]）时 MACE 风险增加相关。
在慢性冠状动脉综合征患者中，升高的 IL-6 水平与所有 CKD 分层的 MACE 风险相关。因此，IL-6 和 CKD 分期可能有助于识别慢性冠状动脉综合征患者，以便进行抗炎治疗。
