The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management

Robert A Hegele; Henry N Ginsberg; M John Chapman; Børge G Nordestgaard; Jan Albert Kuivenhoven; Maurizio Averna; Jan Borén; Eric Bruckert; Alberico L Catapano; Olivier S Descamps; G Kees Hovingh; Steve E Humphries; Petri T Kovanen; Luis Masana; Päivi Pajukanta; Klaus G Parhofer; Frederick J Raal; Kausik K Ray; Raul D Santos; Anton F H Stalenhoef; Erik Stroes; Marja-Riitta Taskinen; Anne Tybjærg-Hansen; Gerald F Watts; Olov Wiklund; European Atherosclerosis Society Consensus Panel

doi:10.1016/S2213-8587(13)70191-8

The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management

Robert A Hegele, Henry N Ginsberg, M John Chapman, Børge G Nordestgaard, Jan Albert Kuivenhoven, Maurizio Averna, Jan Borén, Eric Bruckert, Alberico L Catapano, Olivier S Descamps, G Kees Hovingh, Steve E Humphries, Petri T Kovanen, Luis Masana, Päivi Pajukanta, Klaus G Parhofer, Frederick J Raal, Kausik K Ray, Raul D Santos, Anton F H StalenhoefErik Stroes, Marja-Riitta Taskinen, Anne Tybjærg-Hansen, Gerald F Watts, Olov Wiklund, European Atherosclerosis Society Consensus Panel

Department of Clinical Medicine

313 Citations (Scopus)

Abstract

Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.

Original language	English
Journal	The Lancet Diabetes & Endocrinology
Volume	2
Issue number	8
Pages (from-to)	655-666
Number of pages	12
ISSN	2213-8587
DOIs	https://doi.org/10.1016/S2213-8587(13)70191-8
Publication status	Published - Aug 2014

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10.1016/S2213-8587(13)70191-8

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Hegele, R. A., Ginsberg, H. N., Chapman, M. J., Nordestgaard, B. G., Kuivenhoven, J. A., Averna, M., Borén, J., Bruckert, E., Catapano, A. L., Descamps, O. S., Hovingh, G. K., Humphries, S. E., Kovanen, P. T., Masana, L., Pajukanta, P., Parhofer, K. G., Raal, F. J., Ray, K. K., Santos, R. D., ... European Atherosclerosis Society Consensus Panel (2014). The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. The Lancet Diabetes & Endocrinology, 2(8), 655-666. https://doi.org/10.1016/S2213-8587(13)70191-8

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 & European Atherosclerosis Society Consensus Panel 2014, 'The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management', The Lancet Diabetes & Endocrinology, vol. 2, no. 8, pp. 655-666. https://doi.org/10.1016/S2213-8587(13)70191-8

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abstract = "Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.",

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AU - Hegele, Robert A

AU - Ginsberg, Henry N

AU - Chapman, M John

AU - Nordestgaard, Børge G

AU - Kuivenhoven, Jan Albert

AU - Averna, Maurizio

AU - Borén, Jan

AU - Bruckert, Eric

AU - Catapano, Alberico L

AU - Descamps, Olivier S

AU - Hovingh, G Kees

AU - Humphries, Steve E

AU - Kovanen, Petri T

AU - Masana, Luis

AU - Pajukanta, Päivi

AU - Parhofer, Klaus G

AU - Raal, Frederick J

AU - Ray, Kausik K

AU - Santos, Raul D

AU - Stalenhoef, Anton F H

AU - Stroes, Erik

AU - Taskinen, Marja-Riitta

AU - Tybjærg-Hansen, Anne

AU - Watts, Gerald F

AU - Wiklund, Olov

AU - European Atherosclerosis Society Consensus Panel

PY - 2014/8

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N2 - Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.

AB - Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.

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DO - 10.1016/S2213-8587(13)70191-8

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SN - 2213-8587

VL - 2

SP - 655

EP - 666

JO - Wine Economics and Policy

JF - Wine Economics and Policy

IS - 8

ER -

The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management

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