The consequences of elevated triglycerides range from xanthomas to CVD. Here, a primer on the mechanism of omega-3 fatty acid therapy.
Definitions of Hypertriglyceridemia. Thresholds of hypertriglyceridemia have varied by organization.
Hypertriglyceridemia Defined. Because elevated TG levels may be the result of multiple genetic and secondary risk factors, the 2014 EAS Consensus Panel recommended a definition based on genetic studies.
Common Causes of HTG. Primary causes include familial hyperchylomicronemia and hypertriglyceridemia, combined hyperlipoproteinemia. Secondary causes: Common lifestyle factors (eg, alcohol, poor diet, lack of exercise, obesity, T2DM) and a variety of medications. Medications,
Consequences of HTG. Normal lipid hydrolysis is impaired, prevents clearance of chylomicrons from circulating plasma. TG build-up can lead to various types of organ damage including pancreatitis, cardiovascular disease.
Mechanisms of HTGs in CVD. Activate plasma CETP involved in lipid modeling process that leads to atherosclerosis; increases risk of CVD events, death; also increases risk of cardiac events in patients with HTG taking statins
Impact of Omega-3 Fatty Acids on HTG. Beneficial effects occur through several mechanisms eg, downregulation of VLDL production, reduction of circulating non-esterified fatty acids sent to the liver, increased fatty acid uptake, reduced postprandial hypertriglyceridemia.
Benefits of Dietary Sources of OM3FAs. Diet rich in fish was associated with ↓ LDL-C, ↓ HDL-C, and ↓ TG lipoproteins over 24 months; clinical trials show positive impact on CV events, mortality.
Impact of OM3FA Supplementation on CVD Risks. May not be as effective as dietary sources, but offers additional benefits in reducing TG-associated CV risks--significantly reduced risks of sudden death, MI, cardiac death in patients with pre-existing CVD.
HTG Management with OM3FAs. Guidelines recommend that TG levels less than 150 mg/dL (less than 1.7 mmol/L) are desirable. If levels remain elevated despite lifestyle change/statin therapy, TG-lowering agents (eg, fibrates, OM3FAs) are recommended. OM3FAs reduce both fasting and nonfasting TG levels by 20-50%. OM3FA supplements are recommended for management of hypertriglyceridemia.
Triglycerides (TGs) are the main components of body fat in animals and humans. Composed of the combined esters of three fatty acids and glycerol they are critical sources of energy for metabolic processes (containing more than double the caloric energy of carbohydrates).TGs are either directly ingested from dietary sources or synthesized in the liver from carbohydrate molecules. Large TG molecules are then packaged into very low density lipoprotein (VLDL) particles or are added to chylomicrons that are efficiently broken down to release free fatty acids necessary to metabolic processes. TG remnants of these activities are then cleared by the liver.Any breakdown of this process or overwhelming fat and carbohydrate intake that prodcues inadequate TG clearance results in hypertriglyceridemia.The short slide show above summarizes the mechanisms underlying elevated TGs and the role of omega-3 fatty acids in their treatment.Â References 1.Â Arca M, Borghi C, Pontremoli R, et al. Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention. Nutr Metab Cardiovasc Dis 2018;28:197-205.2. Goldberg AC. Overview of lipid metabolism. Merck Manual. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/overview-of-lipid-metabolism. Accessed 3/19/19.3. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007; 298: 299â230.4. Miller M, Cannon CP, Murphy SA, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2008;51:724â730.5. Ooi EM, Lichtenstein AH, Millar JS, et al. Effects of Therapeutic Lifestyle Change diets high and low in dietary fish-derived FAs on lipoprotein metabolism in middle-aged and elderly subjects. J Lipid Res 2012;53:1958â1967.6. Tholstrup T, Hellgren LI, Petersen M, et al. A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men. J Nutr 2004;134:1051â1057.