Analytical Performance/Clinical Utility Of Laboratory Te

实验室技术的分析性能/临床实用性

• 批准号: 7004765
• 负责人: Gyorgy Csako
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7004765
• 关键词: acute phase protein; analytical method; atherosclerosis; biomarker; blood lipid; blood tests; cardiovascular disorder diagnosis; clinical research; communicable diseases; diagnosis design /evaluation; diagnostic tests; disease /disorder model; disease /disorder proneness /risk; heat shock proteins; human subject; immunoregulation; inflammation; laboratory mouse; lecithin cholesterol acyltransferase deficiency; patient oriented research; phosphatidylcholine sterol acyltransferase; thrombosis

Atherothrombosis is a multifactorial disease and risk factors for atherothrombosis are now estimated to be in the hundreds. In addition to classical risk factors like serum lipids (total cholesterol and triglycerides), lipoproteins (including lipoprotein[a]), apolipoproteins, and a variety of other factors such as infections with corresponding antibodies, autoimmune constituents with corresponding antibodies, inflammatory molecules such as C-reactive protein (CRP), and hemostatic factors have been also considered for risk. Over the past year, we carried out several collaborative studies: (1) In a pilot trial, the effects of thyroid hormones on CRP and hemostasis were assessed in thyroid cancer patients receiving thyroid hormone suppression therapy. At the time of their thyroid scanning, these patients change their thyroid status from extreme hyperthyroid to hypothyroid and back. While on thyroid hormone suppression therapy, the majority of patients exhibited elevated CRP and a prothrombotic profile. These findings are consistent with an increased incidence of atherothrombotic events in hyperthyroidism. (2) In a retrospective study, a large cohort of systemic lupus erythematosus patients (>200) from Johns Hopkins University was evaluated for serum lipoprotein(a) levels (measured by two analytically valid [isoform-independent] methods) and for apolipoprotein(a) isoforms (phenotypes). Data are now being analyzed with respect to association with premature thromboembolic events and other clinical and/or laboratory parameters. If our earlier observation that the presence of medium-sized apolipoprotein(a) isoforms is significantly associated with premature thromboembolic events (164 NIH patients with systemic lupus erythematosus) is validated in a larger, independent patient population, phenotyping for apolipoprotein(a) could become a major tool for identifying systemic lupus erythematosus patients with high risk of atherothrombosis and appropriate prophylactic therapy may be implemented. (3) In other studies: (a) Increased levels of heat-shock protein 70 were associated with low risk of coronary artery disease, while serum antibodies to heat-shock protein 65 correlated with increased coronary calcification. The findings suggest pathogen-triggered autoimmunity in early atherosclerosis and support the view that atherothrombosis is an inflammatory, infectious and/or autoimmune disease. (b) Metabolic syndrome (including elevated CRP) was found in a subset of women with major depressive disorder. This may explain, at least in part, the increased cardiovascular morbidity in these patients.

动脉粥样硬化血栓形成是一种多因素疾病，目前估计动脉粥样硬化血栓形成的危险因素有数百种。除了经典的风险因素如血清脂质（总胆固醇和甘油三酯）、脂蛋白（包括脂蛋白[a]）、载脂蛋白和各种其他因素如相应抗体感染、相应抗体的自身免疫成分、炎症分子如C-反应蛋白（CRP）和止血因素也被认为是风险因素。在过去的一年里，我们进行了几项合作研究：（1）在一项先导试验中，在接受甲状腺激素抑制治疗的甲状腺癌患者中评估了甲状腺激素对CRP和止血的影响。在甲状腺扫描时，这些患者的甲状腺状态从极度甲状腺功能亢进变为甲状腺功能减退，然后又变回来。在接受甲状腺激素抑制治疗时，大多数患者表现出CRP升高和血栓形成前特征。这些发现与甲亢患者动脉粥样硬化血栓形成事件发生率增加一致。(2)在一项回顾性研究中，对来自约翰霍普金斯大学的系统性红斑狼疮患者（>200例）的血清脂蛋白（a）水平（通过两种分析有效的[异构体非依赖性]方法测量）和载脂蛋白（a）异构体（表型）进行了评价。目前正在分析与过早血栓栓塞事件和其他临床和/或实验室参数相关的数据。如果我们早期观察到中等大小载脂蛋白（a）亚型的存在与过早血栓栓塞事件（164例NIH系统性红斑狼疮患者）显著相关，并在更大的独立患者人群中得到验证，载脂蛋白（a）表型可能成为识别系统性红斑狼疮患者动脉粥样硬化血栓形成高风险的主要工具，并可能实施适当的预防性治疗。(3)在其他研究中：（a）热休克蛋白70水平的升高与冠状动脉疾病的低风险相关，而热休克蛋白65的血清抗体与冠状动脉钙化的增加相关。这些发现提示了早期动脉粥样硬化中病原体触发的自身免疫，并支持动脉粥样硬化血栓形成是一种炎症性、感染性和/或自身免疫性疾病的观点。(b)代谢综合征（包括CRP升高）在重度抑郁症女性中发现。这可能至少部分解释了这些患者心血管发病率的增加。