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

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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?).