Analytical and Clinical Studies on Factors Involved in Atherosclerosis

我们继续研究动脉粥样硬化血浆成分和标志物的分析和诊断性能和各自的方法的临床应用。由于已知血浆高密度脂蛋白（HDL）可预防冠状动脉疾病，而血浆低密度脂蛋白（LDL）可致动脉粥样硬化，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脂质调节干预措施非常重要。我们评估了最近可用的均质HDL-C （EZ- hdl）和LDL- C （EZ- LDL）方法在人血清中的分析性能。与传统的非均相（预处理和电泳）脂蛋白-胆固醇方法相比，这些新的均相方法具有相似或更高的精度，但它们与旧方法之间的偏差表明标准化不理想。此外，我们观察到脂血症对这些均质方法的影响比制造商所描述的更为明显。对新采集的标本进行血清脂质和脂蛋白成分的分析并不总是可行的，并且已发表的数据往往相互矛盾或无法用于较新的方法。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（+4℃和-70℃）和重复冻融对各种血脂和脂蛋白胆固醇分数的影响，这些分数是用各种方法测量的。与NHLBI心脏病学分支的一组研究人员合作，我们评估了喹普利、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）对各种血浆脂质、脂蛋白、载脂蛋白、纤维蛋白溶解标志物（如d -二聚体）和炎症标志物（如c -反应蛋白，CRP）的影响。和/或同型半胱氨酸绝经后妇女和/或冠心病（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生和进展中的临床意义。关于载脂蛋白(a)亚型与系统性红斑狼疮（SLE）患者的动脉粥样硬化-血栓形成现象之间可能的关系，白细胞介素对血浆脂质、脂蛋白和载脂蛋白的影响，以及频繁献血（铁负荷降低）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.