Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography.
Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography.
复制标题
DOI：
10.1186/1741-7015-10-157
复制
发表时间：
2012-12-05
期刊：
影响因子：
9.3
通讯作者：
McNamara DM
中科院分区：
文献类型：
--
作者：
LaFramboise WA;Dhir R;Kelly LA;Petrosko P;Krill-Burger JM;Sciulli CM;Lyons-Weiler MA;Chandran UR;Lomakin A;Masterson RV;Marroquin OC;Mulukutla SR;McNamara DM
为了评估冠状动脉解剖和动脉粥样硬化的存在，美国每年进行超过100万例诊断性心导管插入术。这些患者中近一半没有明显的冠状动脉病变或不需要机械或手术血运重建术。因此，使用低成本、低风险的血清生物标志物测试排除临床显著冠状动脉疾病（CAD）的能力，即使是一小部分冠状动脉正常的患者，也可能是非常有益的。359名有症状的受试者接受导管插入术检查血清中参与动脉粥样硬化、动脉粥样硬化和斑块易感性的蛋白。冠状动脉造影对150例不需要经皮介入治疗（PCI）的无血流限制性CAD患者进行了分类，209例需要冠状动脉重建术（支架、血管成形术或冠状动脉搭桥手术）。比较两组患者各分析物的连续变量，包括计算错误发现率（FDR≤1%）和Q值（P值调整为统计学显著性≤0.01）。需要血运重建的患者的循环蛋白包括载脂蛋白B100 （APO-B100）、c反应蛋白（CRP）、纤维蛋白原、血管细胞粘附分子1 （VCAM-1）、髓过氧化物酶（MPO）、抵抗素、骨桥蛋白、白细胞介素(IL)-1β、IL-6、IL-10和n端片段蛋白前体脑利钠肽（NT-pBNP）升高和载脂蛋白A1 （APO-A1）降低，均存在显著差异。使用可调评分函数对239个样本进行训练，并对120个额外样本进行验证，确定了包含多达5种分析物的生物标志物分类签名。共有14个重叠特征对无明显冠状动脉疾病的患者进行分类（38%至59%的特异性），同时对需要血运重建术的患者保持95%的敏感性。骨桥蛋白（14次）和抵抗素（10次）是这些诊断特征中最常见的。验证研究中最有效的蛋白质标记包括骨桥蛋白（OPN）、抵抗素、基质金属蛋白酶7 （MMP7）和干扰素γ (IFNγ)作为四标记面板，而CRP或脂联素（ACRP-30）的添加在五种蛋白质标记中产生类似的结果。CAD患者血清中的蛋白质主要反映(1)急性期阳性、炎症反应和(2)脂质代谢、转运、过氧化和积累的改变。令人惊讶的是，除了OPN升高外，CAD患者血清中生长因子激活或细胞外基质重塑的指标很少。这些数据表明，许多没有明显CAD症状的患者可以通过靶向多重血清蛋白检测来识别，而无需心导管，从而消除了电离辐射暴露，减少了这些患者血管造影检查的经济负担。
More than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial. Serum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI) while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery). Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1%) and Q value (P value for statistical significance adjusted to ≤ 0.01). Significant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100), C-reactive protein (CRP), fibrinogen, vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), resistin, osteopontin, interleukin (IL)-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP) and decreased apolipoprotein A1 (APO-A1). Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity) while maintaining 95% sensitivity for patients requiring revascularization. Osteopontin (14 times) and resistin (10 times) were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures. Proteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.
登录
查看更多内容
影响因子：
37.8
作者：
Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
2.7
作者：
Abdel-Azeez, Hala Abdel-Hameed;Al-Zaky, Manar
通讯作者：
Al-Zaky, Manar
影响因子：
39.2
作者：
Rosenberg S;Elashoff MR;Beineke P;Daniels SE;Wingrove JA;Tingley WG;Sager PT;Sehnert AJ;Yau M;Kraus WE;Newby LK;Schwartz RS;Voros S;Ellis SG;Tahirkheli N;Waksman R;McPherson J;Lansky A;Winn ME;Schork NJ;Topol EJ;PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Investigators
通讯作者：
PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Investigators
影响因子：
37.8
作者：
Wilson, PWF;D'Agostino, RB;Kannel, WB
通讯作者：
Kannel, WB
影响因子：
4.1
作者：
FRANZEN, A;HEINEGARD, D
通讯作者：
HEINEGARD, D