Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community.
Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community.
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DOI：
10.1161/atvbaha.112.301174
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发表时间：
2013-07
期刊：
影响因子：
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通讯作者：
Benjamin EJ
中科院分区：
文献类型：
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作者：
Schnabel RB;Yin X;Larson MG;Yamamoto JF;Fontes JD;Kathiresan S;Rong J;Levy D;Keaney JF Jr;Wang TJ;Murabito JM;Vasan RS;Benjamin EJ
有证据表明，慢性低度炎症和氧化应激与心血管疾病（CVD）和死亡率有关。我们检查了11种代表炎症和氧化应激的已知和新型生物标志物（C-反应蛋白[CRP]、纤维蛋白原、白细胞介素-6、细胞间粘附分子-1 [ICAM-1]、脂蛋白相关磷脂酶A2（质量和活性）、单核细胞趋化蛋白-1、髓过氧化物酶、CD 40配体、P-选择素、肿瘤坏死因子受体II [TNFRII]）与社区重大CVD事件和死亡率的关系。我们研究了3035名参与者（平均年龄61±9岁，53%为女性）。在随访期间（中位数8.9年），253名参与者发生了CVD事件，343人死亡。CRP（根据标准差ln转换的生物标志物报告的风险比[HR]，1.18，95%置信区间[CI] 1.02-1.35;标称P=0.02）和TNFRII（HR 1.15，95% CI; 1.01-1.32;标称P=0.04）保留在重大CVD的多变量校正模型中，但在校正多重检验后不显著。与死亡率相关的生物标志物为TNFRII（HR 1.33，95% CI：1.19-1.49; P<0.0001）、ICAM-1（HR 1.24，95% CI：1.12-1.37; P<0.0001）和白细胞介素-6（HR 1.25，95% CI：1.12-1.39; P<0.0001）。将这些标记物添加到包括传统风险因素的模型中增加了对死亡风险的区分和重新分类（P<0.0001），但对CVD没有。在11种生物标志物中，TNFRII名义上与重大CVD事件相关，并且与全因死亡率显著相关，这使其成为未来研究的有趣目标。TNFRII与CRP联合与CVD相关，与白细胞介素-6联合与死亡率相关，除了CVD危险因素外，还增加了总死亡率的预测能力，但对CVD事件无影响。
Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein [CRP], fibrinogen, interleukin-6, intercellular adhesion molecule-1 [ICAM-1], lipoprotein-associated phospholipase A2 (mass and activity), monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age 61±9 years, 53% women). During follow-up (median 8.9 years), 253 participants experienced a CVD event and 343 died. CRP (hazard ratios [HR] reported per standard deviation ln-transformed biomarker, 1.18, 95% confidence interval [CI] 1.02-1.35; nominal P=0.02) and TNFRII (HR 1.15, 95% CI; 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR 1.33, 95% CI: 1.19-1.49; P<0.0001); ICAM-1 (HR 1.24, 95% CI: 1.12-1.37; P<0.0001), and interleukin-6 (HR 1.25, 95% CI: 1.12-1.39; P<0.0001). The addition of these markers to the model including traditional risk factors increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. Of 11 biomarkers, TNFRII was associated nominally with incident major CVD, and significantly with all-cause mortality, which renders it an interesting target for future research. The combination of TNFRII with CRP in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.