M. John Chapman

Paris, France

M. John Chapman is Research Professor at the University of Pierre and Marie Curie, and Director Emeritus of the National Institute for Health and Medical Research (INSERM), Pitié-Salpétrière University Hospital, Paris, France. Together with Professor Henry Ginsberg (University of Columbia, New York, USA) he has led the EAS Consensus Panel initiative (for full details of the Consensus Panel papers see https://www.eas-society.org/page/consensus_papers ). Professor Chapman undertook his undergraduate studies at Aberdeen University and the Middlesex Hospital Medical School, University of London. He subsequently trained in cardiovascular lipidology at the Cardiovascular Research Institute of the University of California Medical Center, and the Gladstone Foundation for Cardiovascular Disease, San Francisco, USA. He is the recipient of the 2014 European Lipid Science Award and the 2015 Antonio M. Gotto Jr Prize for Atherosclerosis Research from the International Atherosclerosis Society. Present research interests include the relationship of the lipidome and proteome to the functionality of high-density lipoprotein (HDL) particles in health and cardiometabolic disease, and on the development of new anti-atherosclerotic therapeutics targeted to HDL.


Wednesday 29 May 09:30

Evolving concepts for HDL: Light at the end of the tunnel?

The relationship between HDL and cardiovascular disease has had a turbulent history. Evidence from observational studies of an inverse association between HDL cholesterol levels and coronary artery disease risk prompted the notion that increasing HDL levels therapeutically would reduce atherosclerosis. The results of a number of studies involving different therapeutic approaches have, however, been largely negative and led to the demise of the ‘HDL hypothesis’. In addition, recent epidemiologic data have shown that in some clinical settings very high HDL cholesterol levels may correlate with increased atherosclerotic risk.

The key message from these findings is that HDL cholesterol is not an appropriate measure for assessing the relationship between HDL and atherosclerotic cardiovascular disease. Instead, there has been a renewed focus on HDL functionality, including protective effects of HDL on lipid oxidation, endothelial cell functions/integrity, and anti-inflammatory/antiapoptotic effects.  Increased understanding of HDL particle composition with ‘omics’ technologies has also underlined the oversimplification of previous thinking. There is now increasing evidence that modification of the structure and composition of HDL particles in numerous disease states including diabetes, auto-immune disease, and cardiovascular disease, results in functionally defective particles; these changes may also indirectly enhance low-density lipoprotein atherogenicity. Taken together, evidence suggests that improving HDL particle quality rather than HDL quantity may offer alternative therapeutic approaches in the future.

Key references

Rosenson RS, Brewer HB Jr, Barter PJ, Björkegren JLM, Chapman MJ, Gaudet D, Kim DS, Niesor E, Rye KA, Sacks FM, Tardif JC, Hegele RA. HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology. Nat Rev Cardiol 2018;15:9-19.

Feng M, Rached F, Kontush A, Chapman MJ. Impact of lipoproteins on atherobiology: emerging insights. Cardiol Clin 2018;36:193-201.

Muñoz-Hernandez L, Ortiz-Bautista RJ, Brito-Córdova G, Lozano-Arvizu F, Saucedo S, Pérez-Méndez O, Zentella-Dehesa A, Dauteuille C, Lhomme M, Lesnik P, Chapman MJ, Kontush A, Aguilar Salinas CA. Cholesterol efflux capacity of large, small and total HDL particles is unaltered by atorvastatin in patients with type 2 diabetes. Atherosclerosis 2018;277:72-9.

Chapman MJ, Orsoni A, Robillard P, Therond P, Giral P. Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP. J Clin Lipidol 2018;12:784-800.