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Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease

Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease ATVB in Focus Circulating Biomarkers of Atherothrombotic Disease: Biology, Prediction, Causality, and Therapeutic Targeting Series Editor: Peter Libby Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease Philippa J. Talmud, Michael V. Holmes Abstract—Over the last 10 to 15 years, animal and human observational studies have identified elevated levels of both proinflammatory secretory phospholipase A2-IIA and lipoprotein-associated phospholipase A2 as potential risk factors for coronary heart disease. However, Mendelian randomization, a genetic tool to test causality of a biomarker, and phase III randomized controlled trials of inhibitors of theses enzymes (varespladib and darapladib) converged to indicate that elevated levels are unlikely to be themselves causal of coronary heart disease and that inhibition had little or no clinical utility. The concordance of findings from Mendelian randomization and clinical trials suggests that for these 2 drugs, and for other novel biomarkers in future, validation of potential therapeutic targets by genetic studies (such as Mendelian randomization) before embarking on costly phase III randomized controlled trials could increase efficiency and offset the high risk of drug development, thereby facilitating discovery of new therapeutics and mitigating against the exuberant costs of drug development. (Arterioscler Thromb Vasc Biol. 2015;35:00-00. DOI: 10.1161/ATVBAHA.115.305234.) Key http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease

Holmes, Michael V.
Arteriosclerosis, Thrombosis, and Vascular Biology , Volume Publish Ahead of Print – Sep 1, 2015
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Copyright
© 2015 American Heart Association, Inc.
ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/ATVBAHA.115.305234
pmid
26338298
Publisher site
See Article on Publisher Site

Abstract

ATVB in Focus Circulating Biomarkers of Atherothrombotic Disease: Biology, Prediction, Causality, and Therapeutic Targeting Series Editor: Peter Libby Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease Philippa J. Talmud, Michael V. Holmes Abstract—Over the last 10 to 15 years, animal and human observational studies have identified elevated levels of both proinflammatory secretory phospholipase A2-IIA and lipoprotein-associated phospholipase A2 as potential risk factors for coronary heart disease. However, Mendelian randomization, a genetic tool to test causality of a biomarker, and phase III randomized controlled trials of inhibitors of theses enzymes (varespladib and darapladib) converged to indicate that elevated levels are unlikely to be themselves causal of coronary heart disease and that inhibition had little or no clinical utility. The concordance of findings from Mendelian randomization and clinical trials suggests that for these 2 drugs, and for other novel biomarkers in future, validation of potential therapeutic targets by genetic studies (such as Mendelian randomization) before embarking on costly phase III randomized controlled trials could increase efficiency and offset the high risk of drug development, thereby facilitating discovery of new therapeutics and mitigating against the exuberant costs of drug development. (Arterioscler Thromb Vasc Biol. 2015;35:00-00. DOI: 10.1161/ATVBAHA.115.305234.) Key

Journal

Arteriosclerosis, Thrombosis, and Vascular Biology – Wolters Kluwer Health

Published: Sep 1, 2015

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