Korean Circ J.  2016 Mar;46(2):135-144. 10.4070/kcj.2016.46.2.135.

Hypertriglyceridemia and Cardiovascular Diseases: Revisited

  • 1Department of Cardiology, Gachon University Gil Medical Center, Incheon, Korea. kwangk@gilhospital.com
  • 2Department of Cardiology, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
  • 3Department of Cardiovascular Medinine, Hokko Memorial Clinic, Sapporo, Japan.
  • 4Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.


Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids continue to be evaluated and new specialized targeting treatment modulating triglyceride pathways, such as inhibition of apolipoprotein C-III and angiopoietin-like proteins, are being tested with regard to their effects on lipid profiles and cardiovascular outcomes. In this review, we will discuss the role of hypertriglyceridemia, triglyceride-rich lipoproteins and remnant cholesterol on cardiovascular disease, and the potential implications for treatment stargeting hypertriglyceridemia.


Residual cardiovascular risk; Hypertriglyceridemia; Treatment; Cardiovascular disease

MeSH Terms

Apolipoprotein C-III
Cardiovascular Diseases*
Cholesterol, HDL
Epidemiologic Studies
Fatty Acids, Omega-3
Fibric Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Risk Factors
Apolipoprotein C-III
Cholesterol, HDL
Fatty Acids, Omega-3
Fibric Acids


  • Fig The production of TRLs, remnant cholesterol which induces the formation of atherosclerosis. TRLs include chylomicrons, VLDL and IDL. Their major protein component is apolipoprotein B. In the fasting state, only VLDL and IDL are present in plasma, whereas chylomicrons, VLDL and their remnants circulate under non-fasting conditions. TRLs undergoes intravascular hydrolysis by lipoprotein lipase in muscle, adipose tissue, heart and other tissues, where they provide free fatty acids for energy or storage. Upon lipolysis, chylomicrons and VLDL are depleted of TG and enriched in cholesterol, resulting in the formation of chylomicron remnants and VLDL remnants. CETP mediates major lipid transfer and exchange between HDL and TRLs. During this process, cholesteryl esters are transferred from HDL to TRLs and TG move from TRLs to HDL. In addition, the plasma HDL pool involves hydrolysis of TG in VLDL, IDL, and chylomicrons. In this process, which is catalyzed by LPL, phospholipids as well as several apolipoproteins (such as apoCI, CII, CIII) are transferred to HDL. Since most cells can degrade TG, and there are not any cells that can degrade cholesterol, the cholesterol content of TRLs is more likely to be the cause of atherosclerosis and cardiovascular disease rather than raised TG per se. Indeed, cholesterol, rather than TG accumulates in intimal foam cells and in atherosclerotic plaques, and remnant lipoproteins like LDL can enter the arterial intima. In contrast, chylomicrons are too large to enter. LPL activity at the surface of remnant particles, either at the surface of vascular endothelium or within the intima, leads to liberation of free fatty acids, monoacylglycerols, and other molecules, each of which could cause local injury and inflammation. Although other possible mechanisms have been suggested, perhaps the simplest chain of events is that high triglyceride concentrations are a marker for raised remnants rich in cholesterol, which, upon entrance into the intima, leads to low-grade inflammation, foam cell formation, atherosclerotic plaques, and ultimately cardiovascular disease and increased mortality.11) TRLs: triglyceride rich lipoproteins, VLDL: very large density lipoprotein, IDL: intermediate density lipoprotein, TG: triglyceride, LDL: low density lipoprotein, CETP: cholesteryl ester transfer protein, HDL: high density lipoprotein, LPL: lipoprotein lipase, CE: cholesterol ester.


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