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.

这项临床研究的主要假设是低水平的 游离蛋白 S 是血浆中的一种天然抗凝蛋白，与 中年男性心肌梗塞发病率增加。 游离蛋白 S（血浆蛋白 S 中不存在于复合物中的部分） 与 C4b 结合蛋白）是抗凝作用的辅助因子 活化蛋白 C。急性心肌梗塞患者 游离蛋白 S 的水平显着降低。这项研究 如果自由水平较低，将以盲目的、前瞻性的方式确定 蛋白 S 与心肌梗塞发生率增加有关 梗塞。 血浆样本将在 5 年内每年采集 2,350 个 将参加第二诺斯威克公园的 50-59 岁男性 英国医学研究委员会流行病学赞助的心脏研究 和医疗护理单位。 研究的临床终点将被记录 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不知情，直到所有样本都已通过 收集了研究人群的所有死因 裁决的。除游离蛋白 S 外，总蛋白 S 和 C4b 结合 将测量蛋白质。 研究设计将允许评估 低游离蛋白 S 发展之间的时间关系 水平和心肌梗塞的发生以及存在或 游离水平之间不存在生物梯度（剂量反应） 蛋白质S和梗塞的频率。 这两个分析是 对于评估观察到的关联是否是因果关系很重要 低蛋白S是否是心肌梗塞的结果。 在开始之前已定义了游离蛋白 S 的三个水平 研究确定心肌梗死的发生率是否遵循以下规律： 生物梯度。 通过以下方式衡量其他潜在风险标志 其他实验室，例如凝血酶原片段 Fl+2 和因子 X 激活肽，将允许对止血作用进行全面评估 心肌梗塞的危险因素。 如果主要假设证明 正确，可以识别出心肌梗死高危患者 并可以作为未来研究的目标来检查具体的干预措施 治疗。 第二项研究将在女性中进行，以检查蛋白质 S 心肌梗塞的危险因素。