Blankenberg Stefan, McQueen Matthew J, Smieja Marek, Pogue Janice, Balion Cynthia, Lonn Eva, Rupprecht Hans J, Bickel Christoph, Tiret Laurence, Cambien Francois, Gerstein Hertzel, Münzel Thomas, Yusuf Salim
Department of Medicine II, Johannes Gutenberg-University Mainz, Mainz, Germany.
Circulation. 2006 Jul 18;114(3):201-8. doi: 10.1161/CIRCULATIONAHA.105.590927. Epub 2006 Jul 10.
Individual markers of inflammation may add incremental predictive value in the context of conventionally available risk factors. We evaluated the ability of 9 inflammatory biomarkers, microalbuminuria, and N-terminal pro-brain natriuretic peptide (Nt-proBNP) to improve cardiovascular risk prediction beyond that obtained from traditional risk factors in a secondary-prevention population.
We measured biomarkers representing the acute-phase reaction (C-reactive protein, fibrinogen, and interleukin-6), proinflammatory pathways (soluble tumor necrosis factor receptor-1 and -2, soluble interleukin-1 receptor antagonist, and interleukin-18), endothelial activation (soluble vascular adhesion molecule-1 and soluble intercellular adhesion molecule-1), Nt-proBNP, and microalbuminuria in 3199 study individuals of the Heart Outcomes Prevention Evaluation (HOPE) Study and assessed their association with risk of myocardial infarction, stroke, or cardiovascular death (primary outcome, n=501) over 4.5 years of follow-up. In a backward Cox regression procedure that included risk factors and biomarkers, Nt-proBNP (hazard ratio [HR] 1.72 per increment SD, 95% CI 1.39 to 2.12; P<0.0001), soluble intercellular adhesion molecule-1 (HR 1.46, 95% CI 1.19 to 1.80; P=0.0003), microalbuminuria (HR 1.55, 95% CI 1.22 to 1.98; P=0.0004), soluble interleukin-1 receptor antagonist (HR 1.30, 95% CI 1.05 to 1.61; P=0.02), and fibrinogen (HR 1.31, 95% CI 1.05 to 1.62; P=0.02) remained significantly related to the primary outcome. Only inclusion of Nt-proBNP provided incremental information above that obtained by models of traditional risk factors.
Although levels of various inflammatory biomarkers are significantly related to future cardiovascular risk, their incremental predictive value is modest. A model consisting of simple traditional risk factors and Nt-proBNP provided the best clinical prediction in the secondary-prevention population.
在传统可得的风险因素背景下，个体炎症标志物可能会增加预测价值。我们评估了9种炎症生物标志物、微量白蛋白尿和N末端脑钠肽前体（Nt-proBNP）在二级预防人群中超越传统风险因素预测心血管风险的能力。
我们在心脏结局预防评估（HOPE）研究的3199名研究对象中测量了代表急性期反应的生物标志物（C反应蛋白、纤维蛋白原和白细胞介素-6）、促炎途径（可溶性肿瘤坏死因子受体-1和-2、可溶性白细胞介素-1受体拮抗剂和白细胞介素-18）、内皮激活（可溶性血管细胞黏附分子-1和可溶性细胞间黏附分子-1）、Nt-proBNP和微量白蛋白尿，并在4.5年的随访中评估了它们与心肌梗死、中风或心血管死亡风险（主要结局，n = 501）的关联。在一项纳入风险因素和生物标志物的向后Cox回归分析中，Nt-proBNP（每增加1个标准差的风险比[HR]为1.72，95%置信区间为1.39至2.12；P < 0.0001）、可溶性细胞间黏附分子-1（HR 1.46，95%置信区间为1.19至1.80；P = 0.0003）、微量白蛋白尿（HR 1.55，95%置信区间为1.22至1.98；P = 0.0004）、可溶性白细胞介素-1受体拮抗剂（HR 1.30，95%置信区间为1.05至1.61；P = 0.02）和纤维蛋白原（HR 1.31，95%置信区间为1.05至1.62；P = 0.02）仍与主要结局显著相关。只有纳入Nt-proBNP能提供超越传统风险因素模型的增量信息。
尽管各种炎症生物标志物水平与未来心血管风险显著相关，但其增量预测价值有限。在二级预防人群中，由简单传统风险因素和Nt-proBNP组成的模型提供了最佳临床预测。
