Ruggiero Carmelinda, Cherubini Antonio, Ble Alessandro, Bos Angelo J G, Maggio Marcello, Dixit Vishwa D, Lauretani Fulvio, Bandinelli Stefania, Senin Umberto, Ferrucci Luigi
Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
Eur Heart J. 2006 May;27(10):1174-81. doi: 10.1093/eurheartj/ehi879. Epub 2006 Apr 12.
The role of uric acid (UA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that UA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure.
We evaluate a relationship between UA levels and several inflammatory markers in 957 subjects, free of severe renal failure, from a representative Italian cohort of persons aged 65-95. Plasma levels of UA and white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6r), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-alpha) were measured. Complete information on potential confounders was collected using standard methods. WBC (P=0.0001), neutrophils (P<0.0001), C-reactive protein (P<0.0001), IL-1ra (P<0.0001), IL-6 (P=0.0004), sIL-6r (P=0.002), IL-18 (P<0.0001), TNF-alpha (P=0.0008), and the percentage of subjects with abnormally high levels of C-reactive protein (P=0.004) and IL-6 (P=<0.0001) were significantly higher across UA quintiles. After adjustment for age, sex, behaviour- and disease-related confounders, results were virtually unchanged. In subjects with UA within the normal range, UA was significantly and independently associated with neutrophils count, C-reactive protein, IL-6, IL-1ra, IL-18, and TNF-alpha, whereas non-significant trends were observed for WBC (P=0.1) and sIL-6r (P=0.2).
A positive and significant association between UA and several inflammatory markers was found in a large population-based sample of older persons and in a sub-sample of participants with normal UA. Accordingly, the prevalence of abnormally high levels of C-reactive protein and IL-6 increased significantly across UA quintiles.
尿酸(UA)在动脉粥样硬化和动脉粥样血栓形成过程中的作用存在争议。流行病学研究最近表明,UA可能是心血管疾病的危险因素,也是已有心力衰竭患者死亡率的不良预后标志物。
我们评估了来自意大利一个具有代表性的65 - 95岁人群队列的957名无严重肾衰竭受试者的UA水平与几种炎症标志物之间的关系。测量了血浆中UA、白细胞(WBC)、中性粒细胞计数、C反应蛋白、白细胞介素 - 1受体拮抗剂(IL - 1ra)、白细胞介素 - 6(IL - 6)、可溶性IL - 6受体(sIL - 6r)、白细胞介素 - 18(IL - 18)和肿瘤坏死因子 - α(TNF - α)的水平。使用标准方法收集了关于潜在混杂因素的完整信息。在UA五分位数中,WBC(P = 0.0001)、中性粒细胞(P < 0.0001)、C反应蛋白(P < 0.0001)、IL - 1ra(P < 0.0001)、IL - 6(P = 0.0004)、sIL - 6r(P = 0.002)、IL - 18(P < 0.0001)、TNF - α(P = 0.0008)以及C反应蛋白(P = 0.004)和IL - 6(P = < 0.0001)水平异常升高的受试者百分比均显著更高。在对年龄、性别、行为和疾病相关混杂因素进行调整后,结果基本不变。在UA处于正常范围内的受试者中,UA与中性粒细胞计数、C反应蛋白、IL - 6、IL - 1ra、IL - 18和TNF - α显著且独立相关,而在WBC(P = 0.1)和sIL - 6r(P = 0.2)方面观察到不显著的趋势。
在一个基于人群的大型老年样本以及UA正常的参与者子样本中,发现UA与几种炎症标志物之间存在显著的正相关。因此,C反应蛋白和IL - 6水平异常升高的患病率在UA五分位数中显著增加。