Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Thromb Haemost. 2012 Dec;108(6):1220-7. doi: 10.1160/TH12-03-0195. Epub 2012 Sep 26.
Immunological processes are implicated in the multifactorial pathophysiology of heart failure (HF). The multifunctional chemokine fractalkine (CX3CL1) promotes the extravasation of cytotoxic lymphocytes into tissues. We aimed to assess the prognostic value of fractalkine in HF. Fractalkine plasma levels were determined in 349 patients with advanced systolic HF (median 75 years, 66% male). During a median follow-up of 4.9 years (interquartile range: 4.6-5.2), 55.9% of patients died. Fractalkine was a significant predictor of all-cause mortality (p<0.001) with a hazard ratio of 2.78 (95% confidence interval: 1.95-3.95) for the third compared to the first tertile. This association remained significant after multivariable adjustment for demographics, clinical predictive variables and N-terminal pro-B-type natriuretic peptide (NT-proBNP, p=0.008). The predictive value of fractalkine did not significantly differ between patients with ischaemic and non-ischaemic HF aetiology (p=0.79). The predictive value of fractalkine tertiles was not significantly modified by tertiles of NT-proBNP (p=0.18) but was more pronounced in the first and third tertile of NT-proBNP. Fractalkine was also an independent predictor of cardiovascular mortality (p=0.015). Fractalkine levels were significantly lower in patients on angiotensin-converting enzyme inhibitor therapy (p<0.001). In conclusion, circulating fractalkine with its pro-inflammatory and immunomodulatory effects is an independent predictor of mortality in advanced HF patients. Fractalkine improves risk prediction beyond NT-proBNP and might therefore help to identify high risk patients who need special care. Our data indicate the implication of immune modulation in HF pathology.
免疫过程与心力衰竭（HF）的多因素病理生理学有关。多功能趋化因子 fractalkine（CX3CL1）促进细胞毒性淋巴细胞渗出到组织中。我们旨在评估 fractalkine 在 HF 中的预后价值。在 349 名患有晚期收缩性 HF 的患者（中位数年龄为 75 岁，66%为男性）中测定了 fractalkine 的血浆水平。在中位数为 4.9 年（四分位距：4.6-5.2）的随访期间，55.9%的患者死亡。Fractalkine 是全因死亡率的显著预测因子（p<0.001），与第一三分位数相比，第三三分位数的危险比为 2.78（95%置信区间：1.95-3.95）。在对人口统计学、临床预测变量和 N 末端 pro-B 型利钠肽（NT-proBNP）进行多变量调整后，这种相关性仍然显著（p=0.008）。Fractalkine 的预测价值在缺血性和非缺血性 HF 病因患者之间没有显著差异（p=0.79）。Fractalkine 三分位数的预测价值不受 NT-proBNP 三分位数的显著影响（p=0.18），但在 NT-proBNP 的第一和第三三分位数中更为明显。Fractalkine 也是心血管死亡率的独立预测因子（p=0.015）。接受血管紧张素转换酶抑制剂治疗的患者 fractalkine 水平显著降低（p<0.001）。总之，循环 fractalkine 及其促炎和免疫调节作用是晚期 HF 患者死亡率的独立预测因子。Fractalkine 改善了 NT-proBNP 以外的风险预测，因此可能有助于识别需要特殊护理的高危患者。我们的数据表明免疫调节在 HF 病理中的作用。
