Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Bellvitge University Hospital and Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Universitat de Barcelona, Barcelona, Spain; RTI Health Solutions, Pharmacoepidemiology and Risk Management, Barcelona, Spain.
Bellvitge University Hospital and Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Atherosclerosis. 2018 Nov;278:217-225. doi: 10.1016/j.atherosclerosis.2018.09.034. Epub 2018 Oct 4.
We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population.
We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer.
Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23-10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017).
IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.
我们旨在评估白细胞介素 6(IL6)与动脉粥样硬化性心血管疾病(ASCVD)事件、心力衰竭(HF)和其他慢性疾病预测的相关性及其预后价值,研究对象为一个大型的、多民族的、当代人群。
我们纳入了动脉粥样硬化多民族研究(Multi-Ethnic Study of Atherosclerosis,MESA)中的 6617 名参与者(5640 名他汀类药物未使用者,977 名他汀类药物使用者)。主要结局为硬 ASCVD 事件和 HF;次要结局包括全因死亡、心房颤动、静脉血栓栓塞和癌症。
中位随访时间为 13.2 年。Cox 回归分析显示,IL6 水平与 ASCVD 事件、HF 和死亡率之间存在强相关性,尤其是在他汀类药物使用者中。在后者中,在调整了传统危险因素和其他炎症生物标志物(例如,比较第 3 与第 1 个 IL6 三分位的风险因素,hsCRP 调整后 HF 事件的风险比:3.55,95%CI 1.23-10.27)后,相关性仍然很强。虽然 IL6 并不能超越传统危险因素来改善 CHD 的预测,但在他汀类药物使用者中,它改善了中风(C 统计量增加 0.018)、HF 事件(C 统计量增加 0.028,所有研究结果中最大的 C 统计量增加)和全因死亡(C 统计量增加 0.017)的预测。
IL6 与 ASCVD 事件、HF 和全因死亡率之间存在强而独立的相关性,尤其是在他汀类药物使用者中。虽然 IL6 对 CHD 事件预测的预后价值有限,但它可能在预测无症状他汀类药物使用者的中风、HF 和全因死亡方面发挥作用。需要更大的研究来复制这些发现。