慢性肾脏病患者中可溶性肿瘤坏死因子样弱凋亡诱导因子与主要不良心血管事件
Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD.
作者信息
Fernández-Laso Valvanera, Sastre Cristina, Valdivielso Jose M, Betriu Angels, Fernández Elvira, Egido Jesús, Martín-Ventura Jose L, Blanco-Colio Luis M
机构信息
Vascular Research Laboratory, Fundación Jiménez Díaz University Hospital-Health Research Institute, Madrid, Spain; and.
Unit for Detection and Treatment of Atherothrombotic Diseases, Experimental Nephrology Laboratory, Arnau de Vilanova University Hospital, Biomedical Research Institute of Lleida, Lleida, Spain.
出版信息
Clin J Am Soc Nephrol. 2016 Mar 7;11(3):413-22. doi: 10.2215/CJN.07900715. Epub 2016 Jan 4.
BACKGROUND AND OBJECTIVES
Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3-5D (mean age =58±13 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Ankle-brachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.13±1.15 years).
RESULTS
Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P<0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the follow-up, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular events (hazard ratio [HR], 2.40; 95% CI, 1.33 to 4.33; P=0.004) and cardiovascular mortality (HR, 2.67; 95% CI, 1.05 to 6.76; P=0.04).
CONCLUSIONS
Low sTWEAK levels were associated with the presence of carotid atherosclerotic plaques in patients with CKD. Additionally, lower sTWEAK levels were associated with a higher risk of cardiovascular morbidity and mortality.
背景与目的
可溶性肿瘤坏死因子样凋亡微弱诱导剂（sTWEAK）是一种属于肿瘤坏死因子超家族的促炎细胞因子。sTWEAK浓度与慢性肾脏病（CKD）和心血管疾病（CVD）的存在有关。我们推测，sTWEAK水平可能与CKD患者中观察到的动脉粥样硬化斑块、血管钙化及心血管结局的较高患病率相关。
设计、地点、参与者及测量：对1058例CKD 3-5D期患者（平均年龄=58±13岁；665例男性）进行了一项为期4年的前瞻性、多中心、纵向研究，这些患者来自NEFRONA研究（一项关于CVD替代标志物患病率的研究设计）且无任何CVD病史。进行了踝臂指数和B型超声检查以检测颈动脉和/或股动脉粥样硬化斑块的存在，并进行生化测量和sTWEAK评估。对患者进行心血管结局随访（随访时间为3.13±1.15年）。
结果
CKD更晚期的患者sTWEAK水平较低。sTWEAK浓度与颈动脉内膜中层厚度独立且呈负相关。颈动脉粥样硬化斑块患者的sTWEAK水平较低，但股动脉斑块患者并非如此。在对混杂因素进行调整后，sTWEAK最低三分位数与最高三分位数的患者出现颈动脉粥样硬化斑块的比值比（OR）为4.18（95%置信区间[95%CI]，2.89至6.08；P<0.001）。此外，钙化颈动脉粥样硬化斑块患者的sTWEAK水平较低。多变量调整后出现钙化颈动脉斑块的OR为1.77（95%CI，1.06至2.93；P=0.02）。随访后，发生了41例致命和68例非致命心血管事件。在Cox模型中，在控制潜在混杂因素后，sTWEAK浓度最低三分位数的患者发生致命和非致命心血管事件的风险较高（风险比[HR]，2.40；95%CI，1.33至4.33；P=0.004）以及心血管死亡率较高（HR，2.67；95%CI，1.05至6.76；P=0.04）。
结论
低sTWEAK水平与CKD患者颈动脉粥样硬化斑块的存在相关。此外，较低的sTWEAK水平与心血管发病和死亡风险较高相关。
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