Analytical and Clinical Studies on Factors Involved in Atherosclerosis

我们继续研究致动脉粥样硬化的血浆成分和标记物的分析和诊断性能和各自的方法的临床实用性。由于已知血浆高密度脂蛋白（HDL）对冠状动脉疾病具有保护作用，而血浆低密度脂蛋白（LDL）具有致动脉粥样硬化性，因此测量这些脂蛋白的胆固醇（C）含量对于评估心血管风险、诊断脂质紊乱和监测调脂干预是重要的。我们评估了最近可用的同质HDL-C（EZ-HDL）和LDL-C（EZ LDL）方法在人血清中的分析性能。与传统的异质性（预处理和电泳）脂蛋白-胆固醇方法相比，这些新的同质性方法表现出相似或更高的精度，但它们之间的偏差和旧的方法建议不满意的标准化。此外，我们观察到脂血对这些均质方法的影响比制造商描述的更显著。分析血清脂质和脂蛋白成分并不总是可能在新鲜采集的标本和出版的数据往往是矛盾的或不可用的新方法。这促使我们进一步研究这些分析物可能的储存效应。在正在进行的长期储存研究中，我们正在监测储存温度（+4oC和-70oC）和重复冻融对各种血清脂质和脂蛋白胆固醇组分的影响，这些血脂和脂蛋白胆固醇组分是用各种方法测量的。与NHLBI心脏病学分支的一组研究者合作，我们评估了喹那普利、雌激素、降胆固醇疗法（他汀类药物）、抗氧化剂（维生素E）和L-精氨酸（一氧化氮的天然前体）对各种血脂、脂蛋白、载脂蛋白、纤维蛋白溶解标志物（例如，D-二聚体）和炎症（例如，C-反应蛋白，CRP）和/或同型半胱氨酸在绝经后妇女和/或冠状动脉疾病（CAD）患者。在另一项合作中，我们继续研究病毒和细菌感染在动脉粥样硬化发展和进展中的临床意义。对系统性红斑狼疮（SLE）患者载脂蛋白（a）亚型与动脉粥样硬化血栓形成现象之间可能存在的关系，白细胞介素对血脂、脂蛋白和载脂蛋白的影响，频繁献血（铁负荷减少）对各种动脉粥样硬化因子和标志物的可能影响，以及对动脉粥样硬化过程本身的可能影响的进一步研究仍在进行中。

We continued studying atherogenic plasma constituents and markers with respect to analytical and diagnostic performance and clinical utility of the respective methods. Since plasma high-density lipoprotein (HDL) is known to be protective against coronary artery disease and plasma low-density lipoprotein (LDL) is atherogenic, measurement of the cholesterol (C) content of these lipoproteins is important for assessing cardiovascular risk, diagnosing lipid disorders and monitoring lipid-modifying interventions. We assessed the analytical performance of a recently available homogeneous HDL-C (EZ-HDL) and LDL- C (EZ LDL) methods in human sera. Compared to conventional heterogeneous (pretreatment and electrophoretic) lipoprotein- cholesterol methods, these new homo-geneous methods exhibited similar or greater precision but biases between them and the old methods suggested unsatisfactory standardization. Further, we observed that lipemia has more pronounced effect on these homogeneous methods than that described by the manufacturer. Analysis of serum lipid and lipoprotein constituents is not always possible in freshly collected specimens and published data often are conflicting or not available for newer methods. This prompted us to further examine possible storage effects on these analytes. In ongoing long-term storage studies we are monitoring the effect of both storage temperature (+4oC and -70oC) and repeat freezing-thawing on various serum lipids and lipoprotein cholesterol fractions as measured with a variety of methods. In collaboration with one group of investigators of the Cardiology Branch of the NHLBI, we evaluated the effects of quinapril, estrogen, cholesterol-lowering therapies (statins), antioxidants (vitamin E), and L-arginine, the natural precursor of nitric oxide, on various plasma lipids, lipopro-teins, apolipoproteins, markers of fibrinolysis (e.g., D-dimer) and inflammation (e.g., C-reactive protein, CRP), and/or homocysteine in postmenopausal women and/or patients with coronary artery disease (CAD). In another collaboration, we continued studying the clinical significance of viral and bacterial infections in the development and progression of atherosclerosis. Further investigations on a possible relationship between apolipoprotein(a) isoforms and athero-thrombotic phenomena in patients with systemic lupus erythematosus (SLE), and on the effect of interleukins on plasma lipids, lipoproteins and apolipoproteins, and on the possible effect of fre-quent blood donations (reduced iron load) on various atherosclerotic factors and markers, and on the atherosclerotic process itself are still in progress.