Vascular Research Unit, Department of Vascular Surgery, Viborg Hospital, Heibergs Allé 4, DK-8800 Viborg, Denmark.
Atherosclerosis. 2011 Dec;219(2):892-9. doi: 10.1016/j.atherosclerosis.2011.09.016. Epub 2011 Sep 16.
AIM: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has recently been introduced as a potential mediator of cardiovascular disease. We examined the associations between sTWEAK, its scavenger receptor sCD163, sCD163/sTWEAK ratio and risk for long-term all-cause and cardiovascular mortality in patients with lower-extremity peripheral arterial disease (PAD). METHODS: sTWEAK and sCD163 serum levels were measured retrospectively in a cohort of 295 patients with symptomatic PAD followed for 6.1±2.1 years. The endpoints were defined as all-cause or cardiovascular death. The relationship between sTWEAK, sCD163 levels, sCD163/sTWEAK ratio, and times to fatal outcome was examined by Cox proportional hazards analysis. RESULTS: sTWEAK levels were significantly lower (672 (IQR 515; 872)pg/ml vs. 814 (IQR 673; 957)pg/ml, p < 0.0001), and sCD163/sTWEAK ratio significantly higher (0.91 (IQR 0.63; 1.37) vs. 0.77 (IQR 0.55; 1.12), p = 0.008) in patients with critical limb ischemia (CLI) on admission as compared with those with intermittent claudication (IC). During follow-up, 80 (27%) patients died, hereof 33 (11.5%) of cardiovascular causes. Cox regression analysis revealed that an increase of 100 pg/ml of baseline sTWEAK were associated with a decreased risk for all cause [adjusted hazard ratio (HR) 0.89 (95%CI (0.80-0.99)), p = 0.043] and cardiovascular mortality [adjusted HR 0.83 (95% CI (0.69-0.99)), p = 0.038]. The patients with lower sTWEAK concentrations had a higher risk for cardiovascular death being more than two times as great as patients in the two upper tertiles (adjusted HR 2.2, 95% CI (1.06-4.87), p = 0.035). Similarly, the risk of cardiovascular death was 3-fold increased for patients in the upper tertile of sCD163/sTWEAK ratio as comparing with the patients in two lower tertiles (adjusted HR 3.04, 95% CI (1.44-6.43), p = 0.004). The model including sCD163/sTWEAK ratio have shown a significant improvement in accuracy of cardiovascular death prediction (the area under ROC curve 0.79 (0.72-0.86) vs. 0.84 (0.78-0.90), p = 0.019). CONCLUSIONS: Decreased sTWEAK concentration, and increased sCD163/sTWEAK ratio were significantly and independently associated with long-term cardiovascular mortality in patients with lower-extremity PAD.
目的：可溶性肿瘤坏死因子样弱凋亡诱导因子（sTWEAK）最近被认为是心血管疾病的潜在介质。我们研究了 sTWEAK、其清道夫受体 sCD163、sCD163/sTWEAK 比值与下肢外周动脉疾病（PAD）患者长期全因和心血管死亡率的相关性。
方法：回顾性测量了 295 例有症状 PAD 患者的 sTWEAK 和 sCD163 血清水平，随访时间为 6.1±2.1 年。终点定义为全因或心血管死亡。通过 Cox 比例风险分析检查 sTWEAK、sCD163 水平、sCD163/sTWEAK 比值与致命结局之间的关系。
结果：与间歇性跛行（IC）患者相比，入院时患有严重肢体缺血（CLI）的患者 sTWEAK 水平明显降低（672（IQR 515；872）pg/ml 比 814（IQR 673；957）pg/ml，p<0.0001），sCD163/sTWEAK 比值明显升高（0.91（IQR 0.63；1.37）比 0.77（IQR 0.55；1.12），p=0.008）。在随访期间，80（27%）名患者死亡，其中 33（11.5%）例死于心血管原因。Cox 回归分析显示，基线 sTWEAK 增加 100pg/ml 与全因死亡风险降低相关[调整后的危险比（HR）0.89（95%CI（0.80-0.99）），p=0.043]和心血管死亡率[调整后的 HR 0.83（95%CI（0.69-0.99）），p=0.038]。sTWEAK 浓度较低的患者发生心血管死亡的风险更高，是两个上三分位数患者的两倍多（调整后的 HR 2.2，95%CI（1.06-4.87），p=0.035）。同样，sCD163/sTWEAK 比值处于上三分位数的患者发生心血管死亡的风险是处于两个下三分位数患者的 3 倍（调整后的 HR 3.04，95%CI（1.44-6.43），p=0.004）。包括 sCD163/sTWEAK 比值的模型显示，心血管死亡预测的准确性有显著提高（ROC 曲线下面积 0.79（0.72-0.86）比 0.84（0.78-0.90），p=0.019）。
结论：下肢 PAD 患者 sTWEAK 浓度降低和 sCD163/sTWEAK 比值升高与长期心血管死亡率显著相关。
Arterioscler Thromb Vasc Biol. 2010-3-18
Int Urol Nephrol. 2015-12
Clin J Am Soc Nephrol. 2016-3-7
Arterioscler Thromb Vasc Biol. 2020-7-9
J Cell Mol Med. 2018-7-4
Zotero 插件