PROTEIN S AND MYOCARDIAL INFARCTION

蛋白质与心肌梗塞

• 批准号: 3341458
• 负责人: PHILIP Cinnamon COMP
• 金额: $ 3.57万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-06-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341458
• 关键词: British Isles; acute disease /disorder; binding proteins; biomarker; cardiovascular disorder epidemiology; coagulation factor X; data collection; disease /disorder proneness /risk; early diagnosis; enzyme linked immunosorbent assay; female; gene frequency; hemostatics; human middle age (35-64); human subject; longitudinal human study; male; myocardial infarction; plasma; posttranslational modifications; protein C; protein S; protein structure; prothrombin; prothrombin time; tobacco abuse

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.

该临床研究的主要假设是低水平 游离蛋白S，一种天然抗凝剂蛋白在等离子体中，是相关的 中年男性心肌梗塞的发生率增加。 游离蛋白S（血浆蛋白S的一部分不在复杂 使用C4B结合蛋白）是一种辅助因子 活化的蛋白质C.出现急性心肌梗塞的患者 自由蛋白S的水平显着降低。这项研究 如果较低的自由程度，将以盲目的，潜在的方式确定 蛋白质与心肌的发生率增加有关 梗塞。 血浆样品将每年从2,350中获得5年 年龄在50-59岁的男性将成为第二个Northwick公园的参与者 英国医学研究委员会的心脏研究流行病学赞助 和医疗部门。 该研究的临床终点将被记录 致命的和非致命的心肌梗塞。 为了防止潜在的偏见，这 实验室将对临床终点视而不见，直到所有样品都有 已收集，研究人群中的所有死亡原因是 裁定。 LN在游离蛋白S，总蛋白S和C4B结合中添加 将测量蛋白质。 研究设计将允许评估 低游离蛋白S的发展之间的时间关系 水平和心肌梗塞的发生以及存在或 游离水平之间没有生物梯度（剂量反应） 蛋白质S和梗塞的频率。 这两个分析是 评估观察到的关联是因果还是 低蛋白质是否是由于心肌梗塞而发生的。 在启动之前已经定义了三个级别的游离蛋白质 研究以确定心肌梗塞的频率是否确实遵循 生物梯度。 测量其他潜在风险标记 其他实验室，例如凝血酶原片段fl+2和因子x 激活肽将允许对止血的全面评估 心肌梗塞的危险因素。 如果主要假设证明 正确，可以识别出高风险的心肌梗塞的患者 并且可以针对以后的研究来检查特定的干预措施 治疗。 将在女性中进行第二项研究，以检查蛋白质S作为 心肌梗塞的危险因素。