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

在英国和世界范围内，心脏病仍然是导致死亡和残疾的主要原因。控制已知的心脏病原因(如吸烟、高血压和胆固醇水平升高)可大大降低患病风险。这一成功鼓励了人们寻找可能进一步降低风险的新原因，特别是如果测量或改变血胆固醇水平可以改善疾病预测或预防的话。一种被称为LP-PLA2(脂蛋白相关磷脂酶A2？)的血液酶。有没有可能直接导致心脏变窄？S的动脉变窄，引发心脏病发作。最近有几项研究报道了血液中LP-PLA2的数量(或活性)与随后的心脏病风险之间的正相关关系。最近发明了几乎完全阻断LP-PLA2活性的新药(包括在循环血液和动脉中)，并正在进行早期试验。2004年，美国食品和药物管理局批准使用一种测试(称为？Plac？)它测量血液中LP-PLA2的水平。但这项测试还没有被广泛采用，因为目前还不能可靠地知道LP-PLA2测量是否(或在多大程度上)可以在心脏病发作的早期检测中带来有用的改善。目前也不清楚血液中LP-PLA2水平与不同情况下未来心脏病发作的相关性有多大，例如与有心脏病或中风病史的患者相比，在最初健康的成年人中。这些信息对规划LP-PLA2抑制药物的大型试验非常重要。为了帮助为这些和其他关键问题提供答案，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名个体的初始LP-PLA2水平，其中约15,000人自监测以来已患上心脏病或中风。这个独特的数据库将涵盖几乎整个世界？S，可获得关于LP-PLA2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准确、全面和可靠的结果，这些结果将有助于确定：(I)LP-PLA2测量是否值得纳入心脏病的常规筛查测试，以及(Ii)在大型试验中测试新的LP-PLA2抑制药物的最佳方法(例如，可能需要多少人？具有哪些初始特征？)

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?).