Department of Veterans Affairs, Washington, DC, USA.
J Vasc Surg. 2010 Jun;51(6):1498-503. doi: 10.1016/j.jvs.2009.12.068. Epub 2010 Mar 20.
This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death.
Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed.
At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with significantly lower ferritin levels (-29.78 ng/mL; Cohen effect size, -0.47 [t(df, 134) = 2.33, P = .02]). Mean follow-up average ferritin levels were higher in 23 participants who died (132.5 ng/mL; 95% CI, 79.36-185.66) vs 77 survivors (83.6 ng/mL; 95% CI, 70.34-96.90; Wilcoxon P = .05). Mean follow-up IL-6 levels were higher in dead participants (21.68 ng/mL; 95% CI, 13.71-29.66) vs survivors (12.61 ng/mL; 95% CI, 10.72-14.50; Wilcoxon P = .018). Ferritin levels correlated (Pearson) with average IL-6 levels (r = 0.1845; P = .002) and hsCRP levels (r = .1175; P = .04) during the study.
These data demonstrate statistical correlations between levels of ferritin, inflammatory biomarkers, and mortality in this subset of patients with PAD.
本研究描绘了铁蛋白、炎症生物标志物与参加退伍军人事务部（VA）合作研究#410 外周动脉疾病（PAD）的 100 例无癌症患者（FeAST 中的铁和动脉粥样硬化研究）之间相关性。FeAST 是一项前瞻性、随机、单盲临床试验，旨在测试通过放血减少铁储存是否会影响 1227 例 PAD 患者的临床结果，这些患者被随机分为铁减少组或对照组。还通过测量进入研究时和 6 年研究期间的血清铁蛋白水平，在塞拉内华达卫生保健（SNHC）队列中检查了他汀类药物的作用。两组之间的全因死亡率和次要结局（死亡加非致死性心肌梗死和中风）没有差异。主要研究中的铁减少导致与年龄相关的心血管疾病结局、新癌症诊断和癌症特异性死亡的显著改善。
在进入研究时和 6 个月间隔测量肿瘤坏死因子（TNF）-α、TNF-α受体 1 和 2、白细胞介素（IL）-2、IL-6、IL-10 和高敏 C 反应蛋白（hs-CRP），并在 6 年内进行了 6 年的研究。比较进入研究时和研究结束时铁蛋白和脂质的平均水平。回顾了在研究期间死亡的 23 名参与者的临床经过和铁蛋白水平。
在 SNHC 队列中，参与者的平均年龄为 67±9 岁，与 FeAST 相当，亚组参与者随机分配到铁减少组（n=51）或对照组（n=49）的临床和实验室参数相当。在基线时，53 名服用他汀类药物的参与者的平均铁蛋白起始值略低（114.06ng/mL；95%置信区间[CI]93.43-134.69），而 47 名未服用他汀类药物的参与者（127.62ng/mL；95%CI，103.21-152.02）。对铁减少治疗效果进行调整后的随访数据的纵向分析表明，他汀类药物的使用与铁蛋白水平显著降低相关（-29.78ng/mL；Cohen 效应量，-0.47[t(df，134)=2.33，P=0.02]）。在 23 名死亡的参与者中，平均随访铁蛋白水平较高（132.5ng/mL；95%CI，79.36-185.66），而 77 名幸存者（83.6ng/mL；95%CI，70.34-96.90；Wilcoxon P=0.05）。死亡参与者的平均随访 IL-6 水平较高（21.68ng/mL；95%CI，13.71-29.66），而幸存者（12.61ng/mL；95%CI，10.72-14.50；Wilcoxon P=0.018）。铁蛋白水平与平均 IL-6 水平（r=0.1845；P=0.002）和 hsCRP 水平（r=0.1175；P=0.04）在研究期间呈正相关。
这些数据表明，在这组 PAD 患者中，铁蛋白、炎症生物标志物和死亡率之间存在统计学相关性。
