HYPERTRIGLYCERIDEMIA TRIGLYCERIDES HYPERTRIGLYCERIDEMIA

Biosynthesis of membrane lipids and steroids 1 In most tissues Glycerol / glycerol-kinase LIver Adipose tissue: Glycolysis - DHAP Biosynthesis of membrane lipids and steroids 1

SYNTHESIS of MEMBRANE LIPIDS and TRIGLYCERIDS Phosphatydic acid is a COMMON INTERMEDIER of biosynthesis of phospholipids Neutral fats ACYL-GLYCEROL-SYNTHETASE COMPLEX ENDOPLASMIC RETICULUM Phosphatase Diacylglycerol acyltransferase Biosynthesis of membrane lipids and steroids 1

Normal triglyceride level < 150 Borderline-high triglyceride level Classification TG level, mg/dL Normal triglyceride level < 150 Borderline-high triglyceride level 150-199 High triglyceride level 200-499 Very high triglyceride level >500 Source:  National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97.[14]

Gastrointestinal symptoms Hypertriglyceridemia is usually asymptomatic until triglycerides are greater than 1000-2000 mg/dL. Patients may report pain, which is commonly mid epigastric but may occur in other regions, including the chest or back. A history of recurrent episodes of acute pancreatitis is common in patients with severe and uncontrolled hypertriglyceridemia.Triglyceride levels often exceed 5000 mg/dL at the onset of pancreatitis.

Dermatologic symptoms Severe hypertriglyceridemia may cause skin lesions called xanthomas. Patients may report the appearance of any of the following types of xanthomas: Xanthoma striata palmaris: Orange-yellow discolorations of the palmar creases, which in some cases are raised; considered pathognomonic for dysbetalipoproteinemia Tuberoeruptive xanthomas: Nonpainful, raised, erythematous, nodular lesions approximately 0.5 cm in diameter; may be present on the elbows and knees

Xanthoma striata palmaris: Orange-yellow discolorations of the palmar creases, which in some cases are raised; considered pathognomonic for dysbetalipoproteinemia

Dermatologic symptoms Tuberous xanthomas: Larger, coalesced tuberoeruptive xanthomas; raised, moderately firm, nontender lesions predominantly on the elbows and knees Tendon xanthomas: Occur infrequently; more common in familial hypercholesterolemia Eruptive xanthomas: Small nodular papules commonly seen over the trunk, buttocks, and thighs; associated with chylomicronemia syndrome

Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis

Ophthalmologic symptoms Uncommonly, patients may also note the presence of a corneal arcus, which is a grayish white opacification at the periphery of the cornea and/or

xanthelasmas, which are pale yellow, raised lesions around the eyelids.

Diagnostic Considerations When triglycerides are noted to be elevated, always check a fasting blood sugar and HbA1c to rule out uncontrolled diabetes—one of the most frequent causes of hypertriglyceridemia. Management of this condition may make medication to lower the triglycerides unnecessary or, at least, make it easier to normalize.

A diet high in refined carbohydrates can cause hypertriglyceridemia A diet high in refined carbohydrates can cause hypertriglyceridemia. Although cakes, candy, cookies, etc, are an obvious source, the quantity of liquid calories (nondiet soda, juice, alcohol) should also be determined.

In addition, consider conditions such as hypertriglyceridemia with elevations of very low-density lipoprotein (VLDL) with or without chylomicronemia, as well as mixed hyperlipidemia (type IIb hyperlipidemia) with elevations of both low-density lipoprotein (LDL) and VLDL. Note : use of oral contraceptives, beta-blockers, and thiazide diuretics can also raise plasma triglyceride and VLDL levels.

Pharmacologic Therapy

Niacin High-dose niacin (vitamin B-3) (1500 or more mg/d) decreases triglyceride levels by at least 40% and can raise HDL cholesterol levels by 40% or more.

Fibrates

Omega acids Omega-3 fatty acids are attractive because of their low risk of major adverse effects or interaction with other medications. At high doses (≥4 g/d), triglycerides are reduced. A minimum dose of 4 g of omega-3 fatty acids per day may require at least 8-12 capsules. Low doses of EPA and DHA (750-1000 mg/d) that do not affect lipid levels have been demonstrated to lower the increased TG-lowering therapies (eg, fibrates, fish oils containing both EPA and DHA) can substantially increase LDL cholesterol levels in patients with severe hypertriglyceridemia (≥500 mg/dL).

Statins are more effective when taken at bedtime or in the evening. HMG-CoA reductase inhibitors (statins) Note the following : Statins are more effective when taken at bedtime or in the evening. A major reduction in HDL may occur in some patients on combined therapy with fibrates and thiazolidinediones (check HDL levels 1-2 months following initiation of this combination therapy)

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