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: 6675222
• 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/6675222
• 关键词: analytical method; biomarker; blood lipid; blood tests; cardiovascular disorder diagnosis; communicable diseases; diagnosis design /evaluation; diagnostic tests; disease /disorder model; disease /disorder proneness /risk; female; human subject; immunoregulation; inflammation; laboratory mouse; lecithin cholesterol acyltransferase deficiency; patient oriented research; phosphatidylcholine sterol acyltransferase; postmenopause; thrombosis

Studying the analytical performance of various commercial methods (two different ELISAs and an immunoturbidimetric method) for the measurement of lipoprotein(a), we observed analytically and clinically important differences in their standardization. In addition, we found evidence for apolipoprotein(a) isoform-dependence in at least two of three methods, that further questions their clinical utility. In a collaborative study, we studied the possible effect of frequent blood donations on the development of atherosclerosis in healthy adult blood donors. Despite reductions in body iron stores by frequent blood donation, there was no evidence for a reduced risk of atherosclerosis as assessed by carotid artery intimal thickness and a variety of multiple laboratory markers of inflammation. In another collaborative clinical study, we observed that combination of an HMG-CoA reductase inhibitor drug ("statin") with estrogen attenuates the increase in C-reactive protein during estrogen replacement therapy in postmenopausal women. This is of importance because elevated C-reactive protein levels may have inflammatory and thrombotic consequences that compromise any benefit to cardiovascular risk reduction by estrogens. In a third collaborative clinical study, we assessed the effect of hormone replacement therapy on carotid artery compliance in healthy postmenopausal women. We found that a 3-month hormone replacement therapy significantly improved the carotid artery compliance, as determined by magnetic resonance imaging (MRI) and blood pressure measurements. This effect was independent of changes in serum levels of lipids and markers of inflammation, including C-reactive protein. In a fourth collaborative clinical study, we studied the role of angiotensin II type 1 (AT1) receptor in the regulation of cellular adhesion molecules in atherosclerosis. We found that AT1 receptor antagonism induced by the administration of losartan (an AT1 receptor antagonist) selectively modulated the expression of L-selectin on leukocytes, while did not affect other leukocyte and serum adhesion molecules and C-reactive protein. L-selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so it is often decreased in coronary artery disease. In still another collaborative clinical study, we continued studying the relationship between antibodies to various heat-shock proteins and coronary artery disease. Results of this study are being evaluated.

研究了各种商业方法（两种不同的ELISA和免疫比浊法）测量脂蛋白（a）的分析性能，我们观察到其标准化在分析和临床上的重要差异。此外，我们在三种方法中的至少两种中发现了载脂蛋白（a）亚型依赖性的证据，进一步质疑了它们的临床实用性。在一项合作研究中，我们研究了频繁献血对健康成年献血者动脉粥样硬化发展的可能影响。尽管通过频繁献血减少了体内铁储备，但通过颈动脉内膜厚度和多种炎症实验室标志物评估，没有证据表明动脉粥样硬化的风险降低。在另一项合作临床研究中，我们观察到HMG-CoA还原酶抑制剂药物（“他汀类”）与雌激素的组合减弱了绝经后妇女在雌激素替代疗法期间C-反应蛋白的增加。这一点很重要，因为C-反应蛋白水平升高可能会导致炎症和血栓形成，从而损害雌激素降低心血管风险的任何益处。在第三项合作临床研究中，我们评估了激素替代治疗对健康绝经后妇女颈动脉顺应性的影响。我们发现，3个月的激素替代治疗显着改善颈动脉顺应性，通过磁共振成像（MRI）和血压测量确定。这种效应不依赖于血脂和炎症标志物（包括C反应蛋白）血清水平的变化。在第四项合作临床研究中，我们研究了血管紧张素II 1型（AT 1）受体在动脉粥样硬化中调节细胞粘附分子的作用。我们发现，AT 1受体拮抗剂氯沙坦诱导的AT 1受体拮抗剂选择性地调节白细胞上L-选择素的表达，而不影响其他白细胞和血清粘附分子和C-反应蛋白。L-选择素是一种白细胞粘附分子，在白细胞活化后迅速脱落，因此在冠状动脉疾病中经常降低。在另一项合作临床研究中，我们继续研究各种热休克蛋白抗体与冠状动脉疾病之间的关系。目前正在评估这项研究的结果。