Department of Primary Care and Population Health, University College London, London NW3 2PF, UK.
Atherosclerosis. 2011 Jul;217(1):227-33. doi: 10.1016/j.atherosclerosis.2011.03.015. Epub 2011 Mar 24.
Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis.
We measured baseline IL-18 levels in stored serum samples of subjects from a case-control study nested within a prospective study of 5661 men aged 40-59 years recruited from general practices in 18 British towns in 1978-1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls).
IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.64 [corrected] (95% CI 1.48, 1.83) [corrected] after age adjustment, 1.39 (95% CI 1.25, [corrected] 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.53) [corrected] after additional adjustment for inflammatory markers.
Circulating IL-18 is prospectively and independently associated with CVD risk.
先前的研究表明，白细胞介素-18（IL-18）的循环水平可能与普通人群患冠心病（CHD）的风险有前瞻性关系。我们报告了迄今为止最大的前瞻性研究的新数据，并将其与所有已发表的前瞻性研究的数据结合起来进行荟萃分析。
我们在 1978 年至 1980 年期间从英国 18 个城镇的普通诊所招募的 5661 名 40-59 岁男性的病例对照研究嵌套的前瞻性研究中储存的血清样本中测量了基线 IL-18 水平，并对其进行了长达 16 年的随访（中位随访时间为 8.4 年），以了解致命性 CHD 和非致命性心肌梗死（595 例，1238 例对照）的情况。
IL-18 浓度与吸烟、甘油三酯、高密度脂蛋白胆固醇（呈负相关）以及循环中的几种炎症和止血标志物密切相关。与最低三分位相比，基线 IL-18 水平处于最高三分位的男性患 CHD 的年龄调整比值比（OR）为 1.55（95%CI1.21，1.98）；经过血管危险因素的进一步调整后，这一比值比降至 1.30（95%CI0.99，1.69），经过 CRP 和 IL-6 的进一步调整后，这一比值比降至 1.12（95%CI0.84，1.49）。在 CVD 的荟萃分析中，研究之间的相关性（或效应大小）一致；经过年龄调整后，RR 为 1.64（95%CI1.48，1.83）[校正]，经过进一步的危险因素调整后，RR 为 1.39（95%CI1.25，1.55），经过进一步的炎症标志物调整后，RR 为 1.34（95%CI1.17，1.53）[校正]。
循环 IL-18 与 CVD 风险具有前瞻性和独立性的关联。
