Performance Utility Of Tests For Artherothrombosis

在分析研究中，我们开发并评价了用于在单个试管中连续检测多达四种脂质/脂蛋白组分（HDL-胆固醇、载脂蛋白B、总胆固醇和甘油三酯）的均相测定法。这些新方法在筛查心血管高风险受试者方面特别具有成本效益。在动物研究中，我们分析了卵磷脂：胆固醇酰基转移酶（LCAT）缺陷小鼠的实验室和形态学异常。我们发现，这些动物发展血清脂蛋白X，肾小球硬化，动脉粥样硬化，是一个有用的模型，人类LCAT缺乏症。在一项合作临床研究中，我们继续研究致动脉粥样硬化血浆成分和标记物的分析和诊断性能以及整体临床效用。在一系列研究中，我们调查了雌激素、维生素E和选择性雌激素受体调节剂雷洛昔芬对绝经后妇女血管反应性、血脂谱和炎性血管标志物的影响。我们观察了雌激素替代治疗对绝经后冠心病妇女血清炎症标志物的不同影响。在处理各种病毒的临床意义的其他研究中（例如，巨细胞病毒、单纯疱疹病毒、甲型肝炎病毒）和细菌感染（例如，幽门螺杆菌、肺炎衣原体）和炎症过程的总体研究中，我们观察到（a）总病原体负荷影响冠状动脉疾病风险和血清C反应蛋白水平，（B）宿主对巨细胞病毒感染的反应是冠状动脉疾病易感性的决定因素，在炎症和免疫反应类型方面存在性别差异。此外，我们还发现抗人热休克蛋白60的抗体与冠状动脉疾病的存在和严重程度相关，表明动脉粥样硬化形成的自身免疫成分。

In analytical studies, we developed and evaluated homogeneous assays for sequential testing of up to four lipid/lipoprotein constituents (HDL-cholesterol, apolipoprotein B, total cholesterol, and triglycerides) in a single tube. These new methods are particularly cost-effective in screening for subjects with high cardiovascular risk. In animal studies, we analyzed the laboratory and morphologic abnormalities in lecithin:cholesterol acyltransferase (LCAT) deficient mice. We showed that these animals develop serum lipoprotein X, glomerulosclerosis, and atherosclerosis and are a useful model of human LCAT deficiency. In a collaborative clinical studies we continued studying atherogenic plasma constituents and markers with respect to their analytical and diagnostic performance and overall clinical utility. In a series of studies, we investigated the effects of estrogen, vitamin E, and the selective estrogen receptor modulator raloxifen on vascular responsiveness, serum lipid profile, and inflammatory vascular markers in postmenopausal women. We observed divergent effects of estrogen hormone replacement therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management. In other studies dealing with the clinical significance of various viral (e.g., cytomegalovirus, herpes simplex viruses, hepatitis A virus) and bacterial infections (e.g., Helicobacter pylori, Chlamydia pneumoniae) and inflammatory processes in general, we observed that (a) total pathogen burden affects both coronary artery disease risk and serum C-reactive protein levels, and (b) the host response to cytomegalovirus infection is a determinant of susceptibility to coronary artery disease with gender-based differences in inflammation and type of immune response. Further, we found that antibodies to human heat-shock protein 60 are asssociated with the presence and severity of coronary artery disease, indicating an autoimmune component of atherogenesis.