Press Release: European Atherosclerosis Society Consensus Panel Calls for a Simplified Approach to Defining High Triglycerides (Hypertriglyceridaemia)
- In >95% of patients, high triglycerides reflect the burden of the effects of more than 30 genes involved in triglyceride pathways
- Published in Lancet Diabetes & Endocrinology,1 Free to download from 31 January – 28 February 2014 at http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70191-8/fulltext
High triglycerides or blood fats (>1.7 mmol/L or >150 mg/dL) affects about one-third of adults in Europe.2 On the basis of new understanding of the genetics of triglyceride pathways, the European Atherosclerosis Society (EAS) Consensus Panel has called for a simplified re-definition of this common dyslipidaemia.1
Plasma triglycerides are a marker for triglyceride-rich lipoproteins and their remnants, which have a causal role in cardiovascular disease.3 Prompt diagnosis and treatment are essential. However, the variable clinical presentation, incomplete understanding of the aetiology and complex classification have hampered clinical practice.
Now, new molecular genetic analyses have provided important insights. In >95% of cases, hypertriglyceridaemia reflects the cumulative burden of >30 genetic variants, both common variants associated with small effects and rare variants associated with large effects on plasma triglycerides.4-8 Rare autosomal recessive single gene (monogenic) hypertriglyceridaemia results from mutations in 6 different genes associated with triglyceride production and catabolism. Consequently, the EAS Consensus Panel proposes simplifying the definition of hypertriglyceridaemia to 2 categories.
- Mild to moderate hypertriglyceridaemia: plasma triglycerides 2-10 mmol/L (175-885 mg/dL). This category represents most patients and is explained by the cumulative burden of multiple genes, i.e. a multigenic or polygenic cause.
- Severe hypertriglyceridaemia: plasma triglycerides >10 mmol/L (>885 mg/dL). While a few patients have a single large-effect gene variant (i.e. monogenic cause), most have a polygenic susceptibility component often compounded by secondary factors.
The Panel also emphasises the importance of considering secondary causes of elevated triglycerides, which include obesity, metabolic syndrome, diabetes, diet, increased alcohol intake, hypothyroidism, and various medications (including corticosteroids, oral oestrogen, tamoxifen, thiazides, non-cardioselective beta-blockers, bile acid sequestrants, and second-generation antipsychotics). Some of these secondary factors are themselves influenced by a genetic susceptibility component, especially obesity, metabolic syndrome, non-alcoholic fatty liver disease and diabetes.
The Panel recommends a fasting lipid profile for diagnosis, but acknowledges the potential value of nonfasting measurements.9 Because susceptibility to triglycerides and secondary causes tends to cluster in families, biochemical screening and counselling of family members is essential. However, the Panel does not recommend routine genetic testing.
After addressing secondary causes, management priorities depend on the hypertriglyceridaemia category. For mild to moderate hypertriglyceridaemia (2-10 mmol/L or 175-885 mg/dL), the overall aim is to prevent cardiovascular disease, targeting low-density lipoprotein (LDL) cholesterol, in accordance with current guidelines.10 Non-high-density lipoprotein (HDL) cholesterol and apolipoprotein B are secondary treatment targets after attainment of LDL cholesterol goal. For severe hypertriglyceridaemia (>10 mmol/L or >885 mg/dL), the overall aim of management is to reduce triglycerides to prevent acute pancreatitis, then targeting LDL and non-HDL cholesterol targets next.
Consistent with current guidelines, the EAS Consensus Panel emphasises that lifestyle is the mainstay of managing elevated triglycerides, specifically reducing weight, improving diet, reducing alcohol intake and increasing physical activity. Drug treatment of elevated triglycerides should be in line with current guideline recommendations.10
Considering the clinical implications of these new Consensus Panel recommendations, lead author of this Consensus Panel, Professor Robert A. Hegele, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada said: ‘Hypertriglyceridaemia represents a diagnostic and therapeutic challenge for many clinicians. The EAS Consensus Panel believes that this streamlined definition of hypertriglyceridaemia, taking into account recent epidemiologic, genetic and clinical evidence, will provide a simplified framework for clinicians in their routine practice to improve the diagnosis and management of this common dyslipidaemia.’
- Hegele RA, Ginsberg HN, Chapman MJ, Nordestgaard BG, Kuivenhoven JA, Averna M, Borén J, Bruckert E, Catapano AL, Descamps OS, Hovingh GK, Humphries SE, Kovanen PT, Masana L, Pajukanta P, Parhofer KG, Raal FJ, Ray KK, Santos RD, Stalenhoef AFH, Stroes E, Taskinen M-R, Tybjærg-Hansen A, Watts GF, Wiklund O, on behalf of the European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol Early Online Publication, 23 December 2013. doi:10.1016/S2213-8587(13)70191-8.
- Kotseva K, Wood D, De Backer G, De Bacquer D, Pyörälä K, Keil U; EUROASPIRE Study Group. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil 2009;16:121-37.
- Chapman MJ, Ginsberg HN, Amarenco P et al; European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61.
- Hegele RA, Ban MR, Hsueh N et al. A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia. Hum Mol Genet 2009;18:4189–94.
- Johansen CT, Wang J, Lanktree MB et al. An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2011;31:1916–26.
- Johansen CT, Kathiresan S, Hegele RA. Genetic determinants of plasma triglycerides. J Lipid Res 2011;52:189–206.
- Johansen CT, Hegele RA. Genetic bases of hypertriglyceridemic phenotypes. Curr Opin Lipidol 2011;22:247–53.
- Johansen CT, Hegele RA. Allelic and phenotypic spectrum of plasma triglycerides. Biochim Biophys Acta 2012;1821:833–42.
- Nordestgaard BG, Freiberg JJ. Clinical relevance of non-fasting and postprandial. hypertriglyceridemia and remnant cholesterol. Curr Vasc Pharmacol 2011;9:281–6.
- Catapano AL, Reiner Z, De Backer G et al, and the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), and the ESC Committee for Practice Guidelines 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011;217(suppl 1):S1–44.
Notes for Editors
About the European Atherosclerosis Society Consensus Panel
This EAS Consensus Panel, comprised of 25 internationally renowned experts in atherosclerosis and cardiovascular disease, was convened in July 2012 to consider new evidence-based clinical guidance for the screening, diagnosis and clinical management of common genetic dyslipidaemias, specifically familial hypercholesterolaemia and hypertriglyceridaemic states. The Panel is co-chaired by Professor M. John Chapman, University of Pierre and Marie Curie, and Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitié-Salpetriere University Hospital, Paris, France and Professor Henry N. Ginsberg, Irving Institute for Clinical and Translational Research, Columbia University, New York, USA.
Members of the Writing Committee: Co-chairs and Maurizio Averna (University of Palermo, Italy), Jan Borén (Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR), University of Gothenburg, Sweden), Eric Bruckert (Endocrinology and Cardiovascular Disease Prevention, Hôpital Pitié-Salpêtrière, Paris, France), Alberico L. Catapano (University of Milan and Multimedica IRCSS, Milan, Italy), Robert A. Hegele (University of Western Ontario, Canada), G. Kees Hovingh (Academic Medical Center, University of Amsterdam, The Netherlands), Jan Albert Kuivenhoven (University of Groningen, University Medical Center Groningen, The Netherlands), Päivi Pajukanta (David Geffen School of Medicine, University of California Los Angeles, USA), Kausik K. Ray (Cardiovascular Sciences Research Centre, St George’s Hospital NHS Trust, London, UK), Anton F.H. Stalenhoef (Radboud University Medical Center, Nijmegen, The Netherlands), Erik Stroes (Academic Medical Center, Amsterdam, The Netherlands), Marja-Riitta Taskinen (Cardiovascular Research Group, Heart and Lung Centre, Helsinki University Central Hospital and Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland), Anne Tybjærg-Hansen (Rigshospitalet, University of Copenhagen, Denmark).
Other Panel Members: Olivier S. Descamps (Hopital de Jolimont, Belgium), Steve E. Humphries (Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, UK), Petri T. Kovanen (Wihuri Research Institute, Helsinki, Finland), Luis Masana (Sant Joan University Hospital, Universitat Rovira & Virgili, IISPV, CIBERDEM, Reus, Spain), Børge G. Nordestgaard (University of Copenhagen, Herlev Hospital, Denmark), Klaus G. Parhofer (University of Munich, Germany), Frederick J. Raal (University of the Witwatersrand, Johannesburg, South Africa), Raul D. Santos (Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Brazil), Gerald F. Watts (The University of Western Australia, Perth, Australia), Olov Wiklund (Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden).
About the European Atherosclerosis Society
The European Atherosclerosis Society represents nearly 1,000 basic scientists and clinicians. The mission of the EAS is to improve understanding of the causes, treatment and prevention of atherosclerosis.
For further information refer to www.eas-society.org or www.eas-society.org/the-polygenic-nature-of-hypertriglyceridaemia.aspx .