New European Atherosclerosis Society Consensus Panel statement:
‘State of the Art’ on low-density lipoproteins and cardiovascular disease
February 13, 2020, Gothenburg, Sweden – Low-density lipoproteins (LDL) are the key driver of atherosclerosis, the process that underpins cardiovascular complications such as heart attack and stroke. Clinicians dealing with patients with cardiovascular disease have, however, lacked an up-to-date overview of the underlying pathophysiological mechanisms. The European Atherosclerosis Society (EAS) Consensus Panel has addressed this in a new statement, published today in The European Heart Journal. This follow-up to a previous EAS Consensus Panel statement on clinical data for the causal role of LDL in cardiovascular disease,1 represents a unique, valuable resource for clinicians.
Consensus Panel Co-Chair, Professor M. John Chapman, National Institute for Health and Medical Research (INSERM), Sorbonne University, and Pitie-Salpetriere University Hospital, Paris, France explained the need for this new statement. ‘Our understanding of the causal role of LDL in atherosclerotic cardiovascular disease has progressed substantially in recent years. As a consequence, there is the need for an integrated narrative focussing on the complex pathophysiology of this chronic, insidious disease at the molecular, cellular and tissue levels. This rationale provided the impetus for this new consensus statement from the EAS Consensus Panel.
Atherosclerosis is the process by which fatty deposits or plaques build up in blood vessels, eventually leading to heart attacks, strokes, intermittent claudication, and other diseases caused by chronically or acutely reduced blood flow. Already cardiovascular disease accounts for nearly half of all deaths and is a major cause of disability in Europe,2 and its impact will increase as populations grow older, and the prevalence of type 2 diabetes and obesity escalates.
This EAS Consensus Panel comprised 30 world-renowned leaders in lipid and cardiovascular disease research. The Panel reviewed evidence for mechanistic features of atherosclerotic cardiovascular disease which are driven by LDL. Key areas of focus included:
- transcytosis, a type of transcellular transport, and its role in entry of LDL to the artery wall
- Responses in the artery wall to retained LDL
- Genetic aspects of the arterial wall components and susceptibility to atherosclerosis
- Plaque components favouring rupture and thrombosis, and
- How lowering LDL to very low levels may impact the plaque.
Lead author, Professor Jan Borén, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden commented: ‘ It has long been believed that passive filtration is involved in the delivery of circulating LDL into the artery wall, the starting point of atherosclerosis. Recent insights, however, now support the role of transcytosis in promoting entry of LDL into the artery wall via a regulated vesicular pathway, offering the potential for targeting early events in atherosclerosis.’
The implications of this new EAS Consensus Panel statement are critical in offering new directions for therapy. According to Professor Chapman: ‘It is anticipated that emerging mechanistic features of LDL-driven atherosclerotic cardiovascular disease will facilitate identification of new targets integral to its pathophysiology, leading ultimately to novel therapeutics with translation to cardiovascular benefit.’
Low-density lipoproteins cause atherosclerotic cardiovascular disease; pathophysiological, genetic and therapeutic insights. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020; doi:10.1093/eurheartj/ehz962 [link: https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehz962]
Authors: Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon J, Binder CJ, Daemen MJ, Demer LL, Hegele RA, Nicholls SJ, Nordestgaard BG, Watts GF, Bruckert E, Fazio S, Ference BA, Graham I, Horton JD, Landmesser U, Laufs U, Masana L, Pasterkamp G, Raal FJ, Ray KK, Schunkert H, Taskinen M-R, van de Sluis B, Wiklund O, Tokgozoglu L, Catapano AL, Ginsberg HN.
- Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, Hegele RA, Krauss RM, Raal FJ, Schunkert H, Watts GF, Borén J, Fazio S, Horton JD, Masana L, Nicholls SJ, Nordestgaard BG, van de Sluis B, Taskinen MR, Tokgözoglu L, Landmesser U, Laufs U, Wiklund O, Stock JK, Chapman MJ, Catapano AL. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017;38:2459-72.
- Wilkins E, Wilson L, Wickramasinghe K, Bhatnagar P, Leal J, Luengo-Fernandez R, Burns R, Rayner M, Townsend N. European Cardiovascular Disease Statistics 2017. European Heart Network, Brussels. Available at www.ehnheart.org/cvd-statistics/cvd-statistics-2017.html