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Atherosclerosis. 2019 Mar;282:37-44. doi: 10.1016/j.atherosclerosis.2018.12.024. Epub 2018 Dec 28.

LDL triglycerides, hepatic lipase activity, and coronary artery disease: An epidemiologic and Mendelian randomization study.

Author information

1
Division of Angiology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria; Department of Cardiology, Charité Berlin (CBF), Berlin Institute of Health (BIH), And DZHK (German Research Centre for Cardiovascular Research), Partner Site Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
2
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: hubert.scharnagl@medunigraz.at.
3
Department of Internal Medicine 5 (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
4
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
5
Zora Biosciences Oy, Espoo, Finland; Finnish Cardiovascular Research Center Tampere, University of Tampere, Finland; Finnish Clinical Biobank, University Hospital of Tampere, Finland.
6
Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany; DZHK (German Research Centre for Cardiovascular Research), Partner Site Hamburg/Lübeck/Kiel, Lübeck, Germany; University Heart Center Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
7
Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA, 70808, United States.
8
Department of Cardiology, Charité Berlin (CBF), Berlin Institute of Health (BIH), And DZHK (German Research Centre for Cardiovascular Research), Partner Site Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
9
Department of Cardiology, German Heart Center Munich, Technical University Munich and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Lazarettstraße 36, 80636, Munich, Germany.
10
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria; Synlab Academy, Synlab Holding Germany GmbH, P5, 7, 68167, Mannheim, Germany; Department of Internal Medicine 5 (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
11
Mannheim Institute of Public Health, Mannheim Medical Faculty, University of Heidelberg, Ludolf-Krehl-Straße 7-11, 68167, Mannheim, Germany.

Abstract

BACKGROUND AND AIMS:

High concentrations of low density lipoprotein (LDL) triglycerides have been associated with prevalent angiographic coronary artery disease. The present analysis was designed to investigate the association of LDL triglycerides with cardiovascular mortality and to explore possible mechanisms that may link LDL triglycerides to cardiovascular risk.

METHODS:

LDL triglycerides were measured in 3140 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. They were prospectively followed for cardiovascular mortality (median duration 9.9 years). Genome wide association data for LDL triglycerides were available for 2900 LURIC participants. Genetic data and measurements of hepatic lipase activity were available for 478 participants of the HERITAGE Family study. Genome wide association data for cardiovascular disease were available for 184,305 participants of the CARDIoGRAMplusC4D consortium.

RESULTS:

There was a continuous positive association between LDL triglycerides and cardiovascular mortality (hazard ratio for 5th vs. 1st quintile = 2.53, p < 0.001) and this association was similar in males and females. Genome wide association analysis in LURIC revealed that LDL triglycerides were strongly associated with variation in the hepatic lipase region (p < 10-15 for rs1800588 and rs10468017). The LDL triglyceride raising alleles in rs1800588 and rs10468017 were associated with low hepatic lipase activity in HERITAGE and increased cardiovascular risk in CARDIoGRAMplusC4D. Two-sample Mendelian randomization analysis (HERITAGE and CARDIoGRAMplusC4D) using rs1800588 and rs10468017 as instrumental variable suggested that low hepatic lipase activity may cause increased cardiovascular risk (p = 0.013).

CONCLUSIONS:

Low hepatic lipase activity may link high LDL triglycerides to increased cardiovascular risk.

KEYWORDS:

Cardiovascular mortality; HDL; Hepatic lipase; LDL; Triglycerides

PMID:
30685440
PMCID:
PMC6401295
[Available on 2020-03-01]
DOI:
10.1016/j.atherosclerosis.2018.12.024

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