Reliable evaluation of associations between Lp-PLA2 markers and the risk of cardiovascular outcomes

Lp-PLA2 标记物与心血管结局风险之间关联的可靠评估

• 批准号: G0601284/1
• 负责人: John Danesh
• 金额: $ 39.65万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601284%2F1
• 关键词: Reliable; evaluation; associations; between; Lp

Heart attacks remain leading causes of death and disability in the UK and worldwide. Controlling known causes of heart disease (such as smoking, high blood pressure and raised cholesterol levels) substantially cuts the risk of disease. This success has encouraged the search for new causes which might further reduce risk, particularly if, like blood cholesterol levels, measuring or changing them can lead to improvements in disease prediction or prevention.A blood enzyme known as Lp-PLA2 (?lipoprotein-associated phospholipase A2?) may play a direct role in narrowing the heart?s arteries and triggering heart attacks. Several studies have recently reported positive correlations between the amount (or activity) of Lp-PLA2 in the bloodstream and subsequent risk of heart disease. New medicines which almost completely block the activity of Lp-PLA2 (both in circulating blood and in arteries) have recently been invented and are being tested in early trials. In 2004 the US Food and Drug Administration approved for use a test (known as ?PLAC?) which measures blood levels of Lp-PLA2. But this test has not been widely adopted because it is not yet reliably known whether (or to what extent) Lp-PLA2 measurements can lead to useful improvements in the early detection of heart attacks. It is also not clear to what extent blood levels of Lp-PLA2 are correlated with the future occurrence of heart attacks in different situations, such as in initially healthy adults compared with patients who have a history of heart disease or stroke. Such information is important in planning large trials of Lp-PLA2-inhibiting medicines.To help provide answers to these and other key questions, we will pool original data from at least 27 long-term medical surveys which have already recorded initial Lp-PLA2 levels in a total of about 75,000 individuals, of whom about 15,000 have developed heart disease or strokes since monitoring. This unique database will encompass almost the entirety of the world?s available epidemiological knowledge on Lp-PLA2 levels and cardiovascular diseases. Analyses of it will rapidly yield precise, comprehensive and reliable findings that will help to determine: (i) whether or not Lp-PLA2 measurement merits incorporation into routine screening tests for heart disease and (ii) the best way to test new Lp-PLA2-inhibiting medicines in large trials (eg, how many people are likely to be required? with what initial characteristics?).

心脏病仍然是英国和世界范围内死亡和残疾的主要原因。控制已知的心脏病病因（如吸烟、高血压和胆固醇水平升高）可以大大降低患病风险。这一成功鼓励人们寻找可能进一步降低风险的新原因，特别是如果像血液胆固醇水平一样，测量或改变它们可以改善疾病预测或预防。脂蛋白相关磷脂酶A2？）会直接导致心脏狭窄吗的动脉和引发心脏病发作。最近的几项研究报告了血液中Lp-PLA 2的含量（或活性）与随后患心脏病的风险之间的正相关性。几乎完全阻断Lp-PLA 2活性的新药（在循环血液和动脉中）最近已经发明，并正在早期试验中进行测试。2004年，美国食品和药物管理局批准使用一种测试（称为？PLAC？）其测量Lp-PLA 2的血液水平。但这项测试尚未被广泛采用，因为目前还不清楚Lp-PLA 2测量是否（或在多大程度上）可以导致心脏病发作早期检测的有用改进。目前还不清楚Lp-PLA 2的血液水平在多大程度上与不同情况下心脏病发作的未来发生相关，例如与有心脏病或中风史的患者相比，最初健康的成年人。这些信息在计划Lp-PLA 2抑制药物的大型试验中非常重要。为了帮助回答这些问题和其他关键问题，我们将汇集至少27项长期医学调查的原始数据，这些调查已经记录了总共约75，000人的初始Lp-PLA 2水平，其中约15，000人在监测后患上了心脏病或中风。这个独特的数据库将涵盖几乎整个世界？我们对Lp-PLA 2水平和心血管疾病的流行病学知识。对它的分析将迅速产生精确、全面和可靠的结果，这将有助于确定：（i）Lp-PLA 2测量是否值得纳入心脏病的常规筛查试验，以及（ii）在大型试验中测试新的Lp-PLA 2抑制药物的最佳方法（例如，可能需要多少人？有哪些初始特征？）。