Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Eur J Heart Fail. 2013 Jul;15(7):747-55. doi: 10.1093/eurjhf/hft031. Epub 2013 Mar 13.
Chronic heart failure (HF) is in part characterized by immune activation and inflammation, and factors that regulate lymphocyte trafficking and inflammation may contribute to the progression of this disorder. The homeostatic chemokine CCL21 is a potent regulator of T-cell migration into non-lymphoid tissue and may exert inflammatory properties and influence tissue remodelling. We therefore investigated CCL21 levels and association with fatal outcomes in patients with chronic HF.
Plasma CCL21 was measured at randomization in 1456 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and in 1145 from the GISSI-HF trial. Association between CCL21 levels [given below as hazard ratio (HR) with 95% confidence interval (CI) for 1 SD increase] with all-cause (n = 741) or cardiovascular (CV) mortality (n = 576) was evaluated with multivariable Cox proportional hazard models, adjusting for clinical risk factors, C-reactive protein, and NT-proBNP. In multivariable Cox models, CCL21 was associated with higher risk of all-cause mortality (HR 1.16, 95% CI 1.02-1.32; P = 0.020) and CV mortality (HR 1.20, 95% CI 1.08-1.33; P < 0.001). When the two trials were analysed separately, CCL21 had a similar influence on risk prediction. Finally, CCL21 had a modest but significant impact on the discriminatory properties of the model (all-cause mortality, change in Harrell's C-statistic 0.004, P = 0.001; CV mortality, change in C-statistic 0.002, P = 0.002).
Circulating CCL21 was associated with all-cause and CV mortality in two large populations of contemporary patients with chronic HF.
慢性心力衰竭（HF）部分特征为免疫激活和炎症，调节淋巴细胞迁移和炎症的因素可能有助于该疾病的进展。稳态趋化因子 CCL21 是调节 T 细胞向非淋巴组织迁移的有力调节剂，可能发挥炎症特性并影响组织重塑。因此，我们研究了 CCL21 水平与慢性 HF 患者的致命结局的关联。
在 CORONA 试验中，对 1456 名随机入组的患者和 GISSI-HF 试验中的 1145 名患者进行了随机分组时的血浆 CCL21 测量。使用多变量 Cox 比例风险模型评估 CCL21 水平与全因（n = 741）或心血管（CV）死亡率（n = 576）之间的关联[用 1 SD 增加表示为风险比（HR）及 95%置信区间（CI）]，调整临床危险因素、C 反应蛋白和 NT-proBNP。在多变量 Cox 模型中，CCL21 与全因死亡率（HR 1.16，95%CI 1.02-1.32；P = 0.020）和 CV 死亡率（HR 1.20，95%CI 1.08-1.33；P < 0.001）的风险增加相关。当分别分析这两项试验时，CCL21 对风险预测有类似的影响。最后，CCL21 对模型的区分能力有适度但显著的影响（全因死亡率，Harrell's C 统计量变化 0.004，P = 0.001；CV 死亡率，C 统计量变化 0.002，P = 0.002）。
在两个大型当代慢性 HF 患者人群中，循环 CCL21 与全因和 CV 死亡率相关。
