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

Lead Research Organisation: University of Cambridge
Department Name: Institute of Public Health

Abstract

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?).

Technical Summary

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that circulates largely bound to low-density lipoprotein (LDL) and lies directly on the pathogenic sequence from localised inflammation to atherosclerotic lesion formation. The potential applications of Lp-PLA2 markers in the prediction and prevention of cardiovascular diseases have already been recognized by development of a US FDA-approved assay for its measurement, and by discovery (and development) of potent Lp-PLA2 inhibitors that lower enzyme activity in plasma and at vascular sites. But, despite publication of a number of studies generally reporting positive associations between Lp-PLA2 markers and cardiovascular outcomes, more detailed epidemiological evidence is needed in order to help determine reliably the relevance of Lp-PLA2 markers to coronary heart disease (CHD) and other vascular outcomes.

We will pool individual participant (ie, primary) data on Lp-PLA2 markers from at least 27 prospective studies, involving about 15,000 incident cardiovascular outcomes and about 60,000 non-cases in a prospectively designed, systematic meta-analysis. The combined database will also comprise at least 5000 individuals with serial Lp-PLA2 measurements and at least 40,000 individuals with measurements of both Lp-PLA2 mass and activity. The main analyses will involve regression models stratified by study and sex; studies provided as prospective cohort studies will be analysed using Cox?s proportional hazards model. Potential sources of diversity in associations between Lp-PLA2 markers and CHD risk will be explored.

Data emerging from this study will reliably: (i) quantify associations between Lp-PLA2 markers and CHD (and other vascular) outcomes under different circumstances (including characterisation of any dose-response relationships); (ii) determine the incremental predictive ability for CHD of these markers; (iii) clarify their distribution and values in various subgroups of the population; (iv) elucidate the degree of Lp-PLA2 biovariability in different situations; and (v) determine how well different Lp-PLA2 markers correlate with one another. These data should have potentially important and immediate clinical applications. There is a need to evaluate the utility of the FDA-approved Lp-PLA2 mass test (ie, the PLAC test produced by diaDexus, Inc) for CHD screening, which has been widely used in the studies contributing to the present collaboration. In addition, Lp-PLA2 is already a therapeutic target for several novel agents, including SB-480848 (a compound which has demonstrated the ability to reduce Lp-PLA2 activity in phase I and II trials), suggesting that these data may help to inform and optimize the design of planned phase III trials of such agents.

Organisations

Publications

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Ballantyne C. (2007) Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA(2) and cardiovascular diseases in EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION

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Emerging Risk Factors Collaboration (2012) Lipid-related markers and cardiovascular disease prediction. in JAMA

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Lp-PLA2 Studies Collaboration (2007) Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases. in European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology

 
Description Citation of published protocol manuscript
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
 
Description Citation of published protocol manuscript
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in other policy documents
Impact We have influenced international cardiovascular guidelines through evaluation of the incremental value of assessing established and emerging risk factors for risk assessment, including inflammation biomarkers (NEJM 2012), lipids and lipoproteins (JAMA 2012, Lancet 2010), adiposity measures (Lancet 2011), and carotid ultrasound (Lancet 2012).
 
Description LpPLA2 Studies Collaboration
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Title The Lp-PLA2 Studies Collaboration database 
Description A database has been created of harmonised individual participant data records from over 110,000 individuals 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact n/a 
 
Description Lp-PLA2 Studies Collaboration 
Organisation Albert Einstein College of Medicine
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Baylor College of Medicine
Country United States 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Boston University
Department School of Medicine
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Brigham and Women's Hospital
Country United States 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Cardiology Frankfurt-Sachsenhausen
Country Germany 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Central Hospital of Bolzano
Country Italy 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Columbia University Medical Center
Department Neurological Institute of New York
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Erasmus University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Geisinger Medical Centre
Country United States 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation German Cancer Research Center
Country Germany 
Sector Public 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Helmholtz Association of German Research Centres
Department Helmholtz Zentrum Munchen
Country Germany 
Sector Public 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Intermountain Medical Centre
Country United States 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Johannes Gutenberg University of Mainz
Country Germany 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Lund University
Country Sweden 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Malmo University Hospital
Country Sweden 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Mayo Clinic
Country United States 
Sector Charity/Non Profit 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Medical University of Innsbruck
Country Austria 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University Medical Center Freiburg
Country Germany 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of California
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Cambridge
Department MRC Biostatistics Unit
Country United Kingdom 
Sector Public 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Padova
Country Italy 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Rochester
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Texas Southwestern Medical Center
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Texas Southwestern Medical Center
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Ulm
Country Germany 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Vermont
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation University of Washington
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Uppsala University Hospital
Country Sweden 
Sector Hospitals 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 Studies Collaboration 
Organisation Wake Forest University
Department Wake Forest School of Medicine
Country United States 
Sector Academic/University 
PI Contribution i) study conception and design; ii) study coordination and management; iii) data acquisition; iv) communication with industry experts and principal investigators of collaborating studies; v) organization of collaborators' meetings; vi) analysis and interpretation of data; and vii) writing relevant manuscripts.
Collaborator Contribution Investigators from 32 prospective studies shared primary data on 79,000 participants
Impact The Lp-PLA2 Studies Collaboration (LSC) has assessed the associations of circulating levels of Lp-PLA2 with vascular disease risk in greater detail than possible previously. Findings from the LSC have helped better characterize the relevance of Lp-PLA2 to vascular risk and were instrumental in helping GlaxoSmithKline to design the STABILITY trial - a phase-III outcome trial of the Lp-PLA2 inhibitor darapladib for secondary vascular disease prevention in 15,000 high risk patients. These findings were instrumental to GSK's decision in 2008 to launch a £250m programme of trials of Lp-PLA2 inhibitors.
Start Year 2007
 
Description Lp-PLA2 studies collaboration website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A publicly accessible website was built. http://www.phpc.cam.ac.uk/MEU/LSC/

none
Year(s) Of Engagement Activity 2006,2007
 
Description Media interviews 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interviews with representatives of the media to discuss potential implications of findings from the most comprehensive scientific study to date investigating Lp-PLA2 and cardiovascular risk.

Profiling of research by the BBC, Heart.org, and several national newspapers.
Year(s) Of Engagement Activity 2011