PROTEIN S AND MYOCARDIAL INFARCTION

这项临床研究的主要假设是， 游离蛋白S是血浆中的一种天然抗凝蛋白， 中年男性心肌梗死的发病率增加。 游离蛋白S（血浆蛋白S中不与蛋白质复合的部分） 与C4 b结合蛋白）是抗凝血作用的辅助因子， 活化蛋白C急性心肌梗死患者 游离蛋白S的水平显著降低。这次调查 将以设盲、前瞻性方式确定是否存在低水平的游离 蛋白S与心肌梗死发生率增加有关 梗塞 从2，350开始，每年采集血浆样本，持续5年 年龄在50-59岁之间的男性，将参加第二诺思威克公园 由英国医学研究理事会流行病学赞助的心脏研究 医疗护理单位。 将记录研究的临床终点 致死性和非致死性心肌梗死。 为了防止潜在的偏见， 实验室将对临床终点设盲，直至所有样本 研究人群中的所有死亡原因均已收集， 裁定。除了游离蛋白S，总蛋白S和C4 b结合 蛋白质将被测量。 研究设计将允许评估 低游离蛋白S的发展与 水平和心肌梗死的发生以及是否存在或 游离水平之间不存在生物梯度（剂量-反应） 蛋白S和梗死的频率。 这两个分析是 重要的是评估观察到的关联是否是因果关系， 低蛋白S是否是心肌梗死的结果。 在开始研究之前，已经确定了三种水平的游离蛋白S。 研究以确定心肌梗死的频率是否遵循 生物梯度 其他潜在风险标志物的测量， 其他实验室，如凝血酶原片段F1 +2和因子X 激活肽，将允许全面评价止血 心肌梗死的危险因素 如果主要假设证明 正确，可以识别心肌梗死高危患者 并且可以作为未来研究的目标， 疗法 第二项研究将在女性中进行，以检查蛋白S， 心肌梗死的危险因素。

The major hypothesis of this clinical investigation is that low levels of free protein S, a natural anticoagulant protei in plasma, are associated with an increased incidence of myocardial infarction in middle aged men. Free protein S (that portion of plasma protein S which is not in complex with C4b binding protein) is a cofactor for the anticoagulant effect of activated protein C. Patients presenting with acute myocardial infarction have significantly reduced levels of free protein S. This investigation will determine in a blinded, prospective fashion, if low levels of free protein S are associated with an increased incidence of myocardial infarction. Plasma samples will be obtained yearly for 5 years from 2,350 men aged 50-59 years who will be participants in the Second Northwick Park Heart Study sponsored by the British Medical Research Council Epidemiology and Medical Care Unit. Clinical endpoints for the study will be documented fatal and non-fatal myocardial infarction. To prevent potential bias, this laboratory will be blinded to the clinical endpoints until all samples have been collected and all causes of death in the study population have been adjudicated. ln addition to free protein S, total protein S and C4b binding protein will be measured. The study design will permit the assessment of the temporal relationship between the development of low free protein S levels and the occurrence of myocardial infarction and the presence or absence of a biologic gradient (dose-response) between levels of free protein S and the frequency of infarction. These two analyses are important in assessing whether the observed association is causal or whether low protein S occurs as a consequence of myocardial infarction. Three levels of free protein S have been defined prior to initiating the study to determine if the frequency of myocardial infarction does follow a biologic gradient. The measurement of other potential markers of risk by other laboratories, such as prothrombin fragment Fl+2 and factor X activation peptide, will permit a comprehensive evaluation of hemostatic risk factors in myocardial infarction. If the major hypothesis proves correct, patients at high risk of myocardial infarction can be identified and can be targeted for future studies to examine specific intervention therapy. A second study will be conducted in women to examine protein S as a risk factor for myocardial infarction.