Analytical Performance/Clinical Utility Of Laboratory Tests For Atherothrombosis

动脉粥样硬化血栓形成是一种多因素疾病，目前估计有数百种动脉粥样硬化血栓形成的危险因素。除了经典的危险因素如血清脂质(总胆固醇和甘油三酯)、脂蛋白和载脂蛋白，各种炎症分子，如C-反应蛋白和血清淀粉样蛋白A，止血因素和各种特定的细胞类型也被考虑为风险和/或需要处理。在一项合作研究中，我们在久坐不动的女性中寻找血管内皮功能的预测因子以及与心血管风险的潜在关联，在这些女性中，肥胖相关的风险因素可能导致过度的发病率和死亡率。连续90名女性(年龄22-63岁，22名超重，42名肥胖)进行了生命体征和各种实验室参数(血脂、胰岛素、血糖、超敏C反应蛋白和性激素)的测量，并评估了内皮功能。我们发现，在这些久坐不动的女性中，血管内皮功能与心血管风险显著相关，这些女性通常超重或肥胖。即使在没有常规锻炼的情况下，心肺健康，而不是传统的危险因素或体重，是内皮功能的主要预测因素，并建议采用一种可修改的风险方法。在另一项合作研究中，我们在工作场所锻炼计划中调查了久坐职业员工的内皮功能预测因素。由于久坐的劳动力可能会增加未来心血管疾病的风险，我们的目的是确定是否可以通过营养指导和工作场所的日常锻炼来降低风险。72名久坐不动的员工(年龄22-62岁；26名超重)完成了为期3个月的国家心肺血液研究所Keep the Beat计划，测定跑步机运动时的内皮功能、生命体征、实验室数据和最大耗氧量。这项研究的结果表明，在工作场所进行日常锻炼，以及营养信息，都有可衡量的健康益处，包括改善内皮功能，无论是肥胖还是减肥，如果持续下去，这可能会降低心血管风险。在第三项合作研究中，我们发现之前描述的人类细胞上的受体CD36也作为多种细菌的吞噬受体发挥作用，因此在细菌感染中发挥重要作用。在确定该受体的新作用的同时，我们还确定了在人类细胞与细菌相互作用过程中激活的细胞内生化途径。这些发现对动脉粥样硬化具有潜在的重要意义，因为它现在被认为是一种炎症性疾病，革兰氏阴性细菌壁上存在的称为脂多糖或内毒素的有毒成分与动脉粥样硬化过程有关。

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, and apolipoproteins, a variety of inflammatory molecules such as C-reactive protein and serum amyloid A, hemostatic factors and various specific cell types have been also considered for risk and/or require management. In a collaborative study, we searched for predictors of endothelial function and potential association with cardiovascular risk in women with sedentary occupations, in whom obesity-associated risk factors may contribute to excess morbidity and mortality. Ninety consecutive women (age 22-63 years, 22 overweight and 42 obese) had vital signs and a variety of laboratory parameters (lipids, insulin, glucose, high-sensitivity C-reactive protein, and sex hormones) measured along with assessment of endothelial function. We found that endothelial function was significantly associated with cardiovascular risk in these women with sedentary occupations, who were commonly overweight or obese. Even in the absence of routine exercise, cardiorespiratory fitness, rather than conventional risk factors or body mass, was the dominant predictor of endothelial function and suggested a modifiable approach to risk. In another collaborative study, we investigated predictors of endothelial function in employees with sedentary occupations in a worksite exercise program. Since a sedentary work force may be at increased risk of future cardiovascular disease, our purpose was to determine whether risk could be reduced with nutritional guidance and daily exercise at worksite facilities. Seventy-two sedentary employees (aged 22-62 years; 26 overweight) completed 3 months of participation in the Keep the Beat program of the National Heart, Lung and Blood Institute, with determination of endothelial function, vital signs, laboratory data and peak oxygen consumption during treadmill exercise. Results of this study showed that daily exercise achievable in the workplace, along with nutritional information, have measurable health benefits, including improved endothelial function, regardless of adiposity or weight loss, which may decrease cardiovascular risk, if sustained. In a third collaborative study, we found that a previously described receptor on human cells, CD36, also functions as a phagocytic receptor for a variety of bacteria and hence plays an important role in bacterial infections. Along with identification of a new role for this receptor, we also identified the intracellular biochemical pathways that are activated during interaction of human cells with bacteria. These findings are potentially important for atherosclerosis because it is now considered as an inflammatory disease and toxic components called lipopolysaccharides or endotoxins present in the wall of gram-negative bacteria have been implicated in the atherosclerotic process.