PROTEIN S AND MYOCARDIAL INFARCTION

这项临床研究的主要假设是低水平的 血浆中的一种天然抗凝蛋白--游离蛋白S与 随着中年男性心肌梗塞发病率的增加。 游离蛋白S(血浆蛋白S中不含复合体的那部分 与C4b结合蛋白)是抗凝血作用的辅助因子 表现为急性心肌梗死的患者活性蛋白C 显著降低了游离蛋白质S的水平。这项研究 将以盲目、预期的方式确定，如果自由水平较低 S蛋白与心肌梗死发病率的增加有关 脑梗塞。从2350开始，每年采集一次血浆样本，为期5年 50-59岁的男性将参加第二届诺斯威克公园 由英国医学研究理事会流行病学赞助的心脏研究 和医疗护理部。研究的临床终点将被记录在案 致命性和非致命性心肌梗死。为了防止潜在的偏见，这 实验室将对临床终点视而不见，直到所有样本都 以及研究人群中的所有死因都已被收集 已经判决了。除游离蛋白S外，总蛋白S与补体C4b结合 蛋白质将被测量。研究设计将允许评估 低游离蛋白与S发育的时间关系 水平和心肌梗死的发生以及存在或 游离水平之间没有生物梯度(剂量-反应) 蛋白S与脑梗塞的频度。这两个分析是 在评估观察到的关联是因果关联还是 低蛋白S是否因心肌梗死而发生。 在开始之前，S已经定义了三个水平的游离蛋白质 研究确定心肌梗死的频率是否确实遵循 生物梯度。通过以下方式衡量其他潜在的风险标志物 其他实验室，如凝血酶原片段F1+2和因子X 活化肽，将允许全面评估止血 心肌梗死的危险因素。如果主要假设证明 正确，心肌梗死的高危患者可以被识别 并可作为未来研究的目标，以检查具体的干预措施 心理治疗。第二项研究将在女性中进行，以检测S的蛋白质 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.