Kip Kevin E, Marroquin Oscar C, Shaw Leslee J, Arant Christopher B, Wessel Timothy R, Olson Marian B, Johnson B Delia, Mulukutla Suresh, Sopko George, Merz C Noel Bairey, Reis Steven E
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
Am Heart J. 2005 Nov;150(5):900-6. doi: 10.1016/j.ahj.2005.02.002.
Measurement of C-reactive protein (CRP), a marker of inflammation, is recommended to improve cardiovascular disease (CVD) risk stratification. However, no studies have collectively evaluated how inflammatory markers cluster empirically and relate to angiographic coronary artery disease and CVD events.
From the WISE study, 580 women with fasting plasma samples of inflammatory markers (interleukin [IL]-6, IL-18, tumor necrosis factor alpha, transforming growth factor beta, CRP, serum amyloid A [SAA], and intercellular adhesion molecules) were analyzed over a median of 4.7 years follow-up. All women were referred for coronary angiography (1996-2000) to evaluate suspected myocardial ischemia.
In factor analysis, a "proinflammation" factor (cluster) loaded on IL-6, CRP, and SAA (r = 0.63-0.87); a "proinflammation and anti-inflammation" cluster loaded on IL-18 and tumor necrosis factor alpha (r = 0.72, 0.77); and an "immunosuppressive" factor loaded singly on transforming growth factor beta (r = 0.96). No cluster was independently associated with angiographic coronary artery disease. However, quartile increases of the "proinflammation" cluster (IL-6, CRP, and SAA) yielded death rates of 2.6%, 7.2%, 13.1%, 26.6%, respectively (P < .0001). Women with > or = 2 of 3 proinflammation markers in the upper quartile had an adjusted relative risk of death of 4.21 (95% CI 1.91-9.25), a higher conferred risk than any single marker alone, all of which were roughly equally predictive.
Although IL-6, CRP, and SAA all predict CVD risk in women, development of global measures of inflammation and simply counting the number of markers with high levels improve CVD risk stratification. In addition, results indicate that the adverse impact of inflammation may be largely through other mechanisms than promotion of atherogenesis (ie, destabilization of vulnerable plaques).
炎症标志物C反应蛋白（CRP）的检测有助于改善心血管疾病（CVD）风险分层。然而，尚无研究综合评估炎症标志物如何根据经验聚类以及与冠状动脉造影显示的冠心病和CVD事件之间的关系。
在WISE研究中，对580名女性进行了分析，这些女性具有炎症标志物（白细胞介素[IL]-6、IL-18、肿瘤坏死因子α、转化生长因子β、CRP、血清淀粉样蛋白A[SAA]和细胞间黏附分子）的空腹血浆样本，随访时间中位数为4.7年。所有女性均接受冠状动脉造影检查（1996 - 2000年）以评估疑似心肌缺血情况。
在因子分析中，一个“促炎”因子（聚类）与IL-6、CRP和SAA相关（r = 0.63 - 0.87）；一个“促炎和抗炎”聚类与IL-18和肿瘤坏死因子α相关（r = 0.72，0.77）；一个“免疫抑制”因子单独与转化生长因子β相关（r = 0.96）。没有聚类与冠状动脉造影显示的冠心病独立相关。然而，“促炎”聚类（IL-6、CRP和SAA）每增加一个四分位数，死亡率分别为2.6%、7.2%、13.1%、26.6%（P <.0001）。在上四分位数中具有3种促炎标志物中≥2种的女性，校正后的死亡相对风险为4.21（95%CI 1.91 - 9.25），其带来的风险高于任何单一标志物，所有这些标志物的预测能力大致相同。
虽然IL-6、CRP和SAA均能预测女性的CVD风险，但开发炎症的综合测量方法并简单计算高水平标志物的数量可改善CVD风险分层。此外，结果表明炎症的不利影响可能主要通过促进动脉粥样硬化以外的其他机制（即易损斑块的不稳定）来实现。
