Majority of patients with hypertriglyceridemia have no symptoms. The disorder is often identified while working up the patient for some other not related condition. When patients present with hypertriglyceridemia, the following elements must be present in the history:
• Presence of diabetes, for how long and how it is treated
• History of coronary heart disease, aortic aneurysms, peripheral vascular disease or stroke
• Family history of coronary artery disease
• Smoking, how much and for how long
• Hypertension and how it is treated
• Obesity
• Prior diagnosis of hypercholesterolemia

Gastrointestinal symptoms

When levels of triglycerides are > 1,000 mg/dl, patients may complain of abdominal or back pain, which may be indicative of acute pancreatitis. Other associated symptoms include nausea, vomiting, or even shortness of breath.

Dermatologic symptoms

Patients with severe hypertriglyceridemia (>500mg/dl) can also present with:

• Eruptive xanthomas, as 1-3 mm yellow papules that can erupt anywhere but most common on the chest, back and proximal extremity
• Palmar xanthomas, as yellow creases on the palm seen in type lll hyperlipidemia
• Tuberoeruptive xanthomas, as raised nontender reddish lesions that often occur on the knees and elbows
• Tendon xanthomas, very rare and most frequently seen in patients with familial hypercholesterolemia
• Xanthelasma, as yellow small raised lesions in the corner of the eye

Ophthalmologic symptoms

• Rarely elevated triglycerides will present with arcus cornea
• Lipemia retinalis is the finding of lipemic blood in retinal vessels

Elevated levels of chylomicrons can cause chylomicronemia syndrome, which is characterized by recurrent nausea, abdominal pain, vomiting, and pancreatitis. Triglycerides are typically >2,000 mg/dL in this condition.

• Splenomegaly

  There was no family history of consanguinity, splenomegaly, diabetes, or developmental delay. The ruptured spleen weighed 727 g, and splenomegaly was associated with marked sinus histiocytosis spreading apart the lymphoid component. [clinchem.aaccjnls.org]

  The woman was normal weight, and she was not known with any metabolic disorders, but she had idiopathic splenomegaly, which might be explained by the high triglyceride levels. [portal.findresearcher.sdu.dk]

• Inflammation

  Frequently, patients have lipemic serum with normal to mildly elevated amylase and lipase and with some evidence of pancreatic inflammation on imaging studies. [healio.com]

  Other drugs that suppress the immune system may reduce inflammation of the blood vessels. These include azathioprine, methotrexate, and mycophenolate. For severe disease, rituximab (Rituxan) may be used. [mclaren.org]

  RESULTS AND CONCLUSION: Our results provide preliminary evidence as to favorable effects of EPI on glycemia homeostasis, lipid profile and systemic inflammation such bioactive actions are not class-effects (i.e. limited to their antioxidant potential) [ncbi.nlm.nih.gov]

  As well as hypertriglyceridemia affecting the heart and blood vessels, it also increase the risk of pancreatitis or inflammation of the pancreas, the gland that produces insulin to control the blood glucose level. [news-medical.net]

  AstraZeneca AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation [astrazeneca-us.com]

• Weakness

  OM3-CA increased selectively the concentration of LDL that does not contain apoCIII, a subspecies with a weak relation to coronary heart disease. [ncbi.nlm.nih.gov]

  Emergency symptoms include: Changes in pupil size Loss of function of an arm, leg, or other body part Speech problems Swallowing difficulty Weakness Severe abdominal pain Prevention There is no known way to prevent this disorder. visHeader References [mclaren.org]

  Serious adverse events include myopathy (defined as muscle pain or weakness and 10-fold elevations in creatinine kinase), which is rare ( 76,77 The NLA Statin Safety Task Force has evaluated and published risks and recommendations associated with potential [cmecorner.com]

  The immunoglobulins in control plasma from Patient 3 had weak and nonspecific binding to cells and did not block lipoprotein lipase binding ( Figure 4B ). Figure 5. Figure 5. [doi.org]

• Coronary Atherosclerosis

  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987; 257 :3233–3240. doi: 10.1001/jama.1987.03390230069027. [ PubMed ] [ CrossRef ] [ Google Scholar ] 58. [ncbi.nlm.nih.gov]

  Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation. 2000 ; 101 : 477–484. [circ.ahajournals.org]

• Abdominal Pain

  The severe hypertriglyceridemia was treated with 1 course of plasmapheresis, which corrected the triglyceride level and was temporally associated with improvement of the abdominal pain and renal dysfunction. [ncbi.nlm.nih.gov]

• Recurrent Abdominal Pain

  In some cases, extremely high levels of chylomicrons can cause chylomiconemia syndrome, which is characterized by recurrent abdominal pain, nausea, vomiting, and pancreatitis. Triglycerides are typically >2000 mg/dL in this condition. [jabfm.org]

  Clinical features include failure to thrive, eruptive xanthomas over extensor surfaces and buttocks, lipemia retinalis, hepatosplenomegaly, recurrent abdominal pain, nausea and vomiting, and risk of acute pancreatitis [ 10, 11 ]. [ncbi.nlm.nih.gov]

• Chronic Abdominal Pain

  CONCLUSION: Long-term PEx is effective in preventing the recurrence of acute pancreatitis and in treatment of chronic abdominal pain in this patient with chylomicronemia syndrome. [ncbi.nlm.nih.gov]

• Hypertension

  […] β-blockers are commonly used therapies after acute myocardial infarction and in the management of congestive heart failure and hypertension. [ncbi.nlm.nih.gov]

• Vascular Disease

  disease at 30–50 years Homozygotes: total chol >13 (>500) LDL IIa Usually develop xanthomas and vascular disease in childhood Familial defective apo B-100 Heterozygotes: total chol = 7–13 (275–500) LDL IIa Polygenic hypercholesterolemia Total chol = [accessmedicine.mhmedical.com]

  Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. [ingentaconnect.com]

  High serum triglyceride levels are associated with vascular disease, but whether the relationship is causal remains uncertain (1). [annals.org]

  Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. [ncbi.nlm.nih.gov]

• Hepatomegaly

  The constellation of clinico-pathological and laboratory findings including massive hepatomegaly, steatosis, and marked hypertriglyceridemia in infancy is extremely rare. [ncbi.nlm.nih.gov]

  Triglyceride concentrations >1000 mg/dL are associated with lipemic plasma, eruptive xanthomas, hepatomegaly and ... more The Medical Letter is a subscriber-funded nonprofit organization that publishes critical appraisals of new prescription drugs and [secure.medicalletter.org]

  There were no xanthomata or xanthelasmata and no hepatomegaly. Left ventricular ejection fraction by echocardiogram was normal at 50%. [clinchem.aaccjnls.org]

  Diagnosis On examination, findings may be normal, or they may include the following: GI: Tenderness to palpation over mid-epigastric or upper right/left quadrants; hepatomegaly Dermatologic: Eruptive xanthomas on back (see the image below), buttocks, [emedicine.com]

• Hepatosplenomegaly

  INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory condition characterized by fever, cytopenias, hepatosplenomegaly and hemophagocytosis. [ncbi.nlm.nih.gov]

  Lymphadenopathies, hepatosplenomegaly, and/or bleeding were absent. Aside from elevated triglycerides (1739 mg/dL; normal range, 150-199 mg/dL), an extensive diagnostic workup was unremarkable. [bloodjournal.org]

  Some forms of primary hypertriglyceridemia can lead to specific symptoms: both familial chylomicronemia and primary mixed hyperlipidemia include skin symptoms (eruptive xanthoma), eye abnormalities (lipemia retinalis), hepatosplenomegaly (enlargement [en.wikipedia.org]

  Asymptomatic; may be associated with increased risk of vascular disease Familial lipoprotein lipase deficiency TG >8.5 (>750) (plasma may be milky postprandially) Chylomicrons I, V May be asymptomatic; may be associated with pancreatitis, abdominal pain, hepatosplenomegaly [accessmedicine.mhmedical.com]

• Myopathy

  Current overview of statin-induced myopathy. Am J Med. 2004;116(6):408-16. [revistaendocrino.org]

  Serious adverse events include myopathy (defined as muscle pain or weakness and 10-fold elevations in creatinine kinase), which is rare ( 76,77 The NLA Statin Safety Task Force has evaluated and published risks and recommendations associated with potential [cmecorner.com]

  Statin-associated myopathy. JAMA. 2003;289:1681–90. 19. Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation. 2005;111:3051–7. 20. [aafp.org]

  It is important to be aware that addition of fibrate with statins does increase the risk of hepatotoxicity and myopathy. This combination should be avoided in elderly individuals or in patients with chronic kidney disease. [symptoma.com]

  However, physicians should add fibrates with great caution as combining them with the HMG-CoA reductase inhibitors increases the risks of severe myopathy and hepatoxicity. [jabfm.org]

• Lipemia Retinalis

  An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. [ncbi.nlm.nih.gov]

  Goldberg pointed out common signs seen in patients with severely high triglycerides (TGs): Eruptive xanthomas Pancreatitis Lipemia retinalis (creamy-looking eyes) Retrospective Analysis on Patients with Severe Hypertriglyceridemia The second presentation [raredr.com]

  Some forms of primary hypertriglyceridemia can lead to specific symptoms: both familial chylomicronemia and primary mixed hyperlipidemia include skin symptoms (eruptive xanthoma), eye abnormalities (lipemia retinalis), hepatosplenomegaly (enlargement [en.wikipedia.org]

  Lipemia retinalis is the visualization of lipemic blood in the retinal blood vessels. [jabfm.org]

• Xanthoma

  An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. [ncbi.nlm.nih.gov]

  Familial dysbetalipoproteinemia causes larger, tuberous xanthomas; these are red or orange and occur on the elbows and knees. Palmar crease xanthomas may also occur.The diagnosis is made on blood tests, often performed as part of screening. [en.wikipedia.org]

  Total chol = 6.5–9.0 (250–350) LDL IIa Usually asymptomatic until vascular disease develops; no xanthomas Isolated Hypertriglyceridemia Familial hypertriglyceridemia TG = 2.8–8.5 (250–750) (plasma may be cloudy) VLDL IV Asymptomatic; may be associated [accessmedicine.mhmedical.com]

• Xanthelasma

  Hypertriglyceridemia does not usually present with symptoms until the level reaches 1000 to 2000 mg/dL, at which point the signs and symptoms may include: Gastrointestinal pain Difficulty breathing Memory loss Dementia Xanthelasmas - yellowish deposits [news-medical.net]

  Xanthelasma palpebrarum: a marker of premature atherosclerosis (risk of atherosclerosis in xanthelasma). Postgrad Med J. 2012 Apr. 88(1038):198-204. [Medline]. Rohrich RJ, Janis JE, Pownell PH. [emedicine.com]

• Uremia

  […] look for patients with a genetic predisposition such as type V hyperlipidemia (elevation of chylomicrons and very-low-density lipoprotein [VLDL]) and coexisting secondary causes of hypertriglyceridemia such as alcohol use, diabetes, hypothyroidism, uremia [healio.com]

  The ongoing uremia impairs lipolysis and is associated with elevated VLDL. [symptoma.com]

  Uremia is associated with elevated VLDL, which reflects impaired lipolysis, possibly from the toxic effect of uremic metabolites. Pregnancy. [doi.org]

  […] associated with HTG are covered in depth elsewhere [ 1 ] but briefly, these include: obesity, metabolic syndrome, diet with high positive energy-intake balance and high fat or high glycemic index, alcohol consumption, diabetes (mainly type 2), renal disease (uremia [ncbi.nlm.nih.gov]

Diagnostic Evaluation
The NCEP guidelines recommend the following investigations:

• Fasting lipid panel that includes total cholesterol, LDL, HDL and triglyceride levels. The monitoring should be started at age 20 and repeated every 5 years.
• Individuals who are healthy and have no risk factors need non-fasting total cholesterol and HDL cholesterol every 5 years.
• Patients with ischemic heart disease, familial dyslipidemia or other risk factors for ischemic heart disease need a fasting lipid panel every 12 months.
• In an individual who has a triglyceride level > 150 mg/dl, the study should be repeated again after a 12 hour fast to confirm the result. If the triglyceride levels are greater than 1,000mg/dl, then quantification is needed to determine the exact type of dyslipidemia.

To investigate for the metabolic syndrome, the patient should be evaluated for:

• Fasting hyperglycemia
• Hypertension
• HDL levels
• Obesity

Other tests

• Creatinine and BUN
• Urine analysis
• Thyrotropin levels
• Baseline liver function
• If pancreatitis is suspected, amylase and lipase levels
• Fasting insulin levels to assess for insulin resistance (level > 15 μU/mL is abnormal)
• Also obtain fasting glucose to fasting insulin ratios (< 4.5 is indicative of insulin resistance)

• Dyslipidemia

  In the United States, the 2 most common dyslipidemias are Fredrickson type IIb (familial combined hyperlipidemia) and type IV (familial hypertriglyceridemia). Together, these 2 dyslipidemias account for 85% of familial dyslipidemias. Table 2. [jabfm.org]

  Dyslipidemia is the most common lipid metabolism disorder in humans, and its etiology remains elusive. Hypertriglyceridemia (HTG) is a type of dyslipidemia that contributes to atherosclerosis and coronary heart disease. [ncbi.nlm.nih.gov]

• Hypercholesterolemia

  Hyperlipoproteinemia may be characterized by hypercholesterolemia, isolated hypertriglyceridemia, or both ( Table 189-1 ). [accessmedicine.mhmedical.com]

  The review on familial hypercholesterolemia focused on heterozygous familial hypercholesterolemia. [doi.org]

  […] long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia [ncbi.nlm.nih.gov]

A major reason to treat hypertriglyceridemia is to prevent pancreatitis. The triglyceride level should be reduced to <500 mg/dL to prevent this serious disease. The other reason to treat hypertriglyceridemia is to lower the risk of heart disease [6] [7] [8] [9].

Non pharmacologic treatment

• Many patients with hypertriglyceridemia are frequently obese, have insulin resistance diabetes or have hypertension, all risk factors for heart disease. Thus, the treatment includes dietary changes, weight reduction and regular exercise. Dietary modifications should include decreased overall intake, of fat and refined carbohydrates.
• Alcohol consumption should be decreased or eliminated.
• Discontinuation of any offending medications should be considered as well.
• Both hypothyroidism and diabetes should be treated as it also has a major impact on triglyceride levels

Diet as per NCEP should be:

• Protein 15-20%
• Carbohydrate 55-60%
• Fats 20% or lower

Fish supplements

Fish supplements should not be used as monotherapy but can be used to compliment the medical benefits of the fibrates. Only in very mild cases of hypertriglyceridemia can fish oil supplements be used as monotherapy. A dose of 2-4 gram of fish oil supplement may be required to lower the triglyceride levels by about 25%. It is important to note that this dose of omega 3 fatty acids may raise the LDL by 5-10 % and have no effect on HDL levels. Fish oil can be taken at any time of the day, with or without food. Patients should be warned that as the capsule dissolves in the stomach, it releases the oil that produces a "fish burp”, followed by a fishy breath. Thus it is best to take the omega 3 fatty acids at bed time. To prevent the fishy odor one should freeze the pills or take them with food to minimize the fishy burp and smell.

Drug treatment

Many guidelines exist on management of hypertriglyceridemia. If the patient only has isolated hypertriglyceridemia, fibrate like fenofibrate and gemfibrozil can be prescribed. Many people do not have isolated hypertriglyceridemia but also have elevations in LDL. In these cases statins can be used to decrease the levels of LDL. The statin can be combined with either a fibrate or niacin. It is important to be aware that addition of fibrate with statins does increase the risk of hepatotoxicity and myopathy. This combination should be avoided in elderly individuals or in patients with chronic kidney disease. Others who should not be prescribed combination of statin and fibrate are those already on multiple medications or those prone to dehydration.

If the individual has a mixed dyslipidemia that is associated with hypertriglyceridemia and low HDL, niacin may be an option. There are several formulas of niacin on the market. The immediate acting formula needs to be taken three times a day and is often associated with adverse effects like flushing, GI side effects and hyperglycemia. The long acting formula is taken once a day and has the least amount of adverse effects. However, it has a slow absorption and long duration of action. It also carries a higher risk of liver injury and hence is not recommended. The best formula is the intermediate extended release formula. Niacin has been shown to decrease triglyceride levels by about 25% and also raise HDL levels by about 30%. To decrease the flushing, starting with a low dose taken with a meal is recommended. In addition, aspirin taken 30-60 minutes prior to taking niacin can reduce the incidence of flushing. Niacin has to be used with caution in patients with diabetes and gout. The drug is also contraindicated in the presence of active peptic ulcer disease.

Patients with severe hypertriglyceridemia (>1,000mg/dl) will require combination of medications to lower the levels. In addition, these patients need to adhere to a very low fat diet and complete avoidance of alcohol. The use of bile acid binding agents like cholestyramine (to lower LDL) should not be used as they can worsen the hypertriglyceridemia.

Emerging treatments

Rimonabant is a cannabinoid 1 receptor antagonist that has been shown to reduce food cravings in several randomized trials. The drug has been shown to improve metabolic biomarkers including triglycerides. Unfortunately the drug does have adverse effects like anxiety and depression.

Follow up

Once medical therapy has been started, patients need follow up visits every 1-2 months to have their blood tested for lipid levels. The full effects of the drugs are usually seen at around 4-6 weeks. At this point, the drug dosage levels may also need to be titrated. At the same time, it is important to assess liver function in patients on statins. Individuals who have been prescribed niacin should have their uric acid and blood sugar levels also measured.

All healthcare workers should monitor patients with hypertriglyceridemia for the metabolic syndrome. At regular intervals, these patients should have measurement of the fasting blood sugar, blood pressure and body weight. A visit to a dietitian is recommended to help educate the patient on foods to avoid. Finally, every attempt must be made to assist the patient discontinue smoking and lower the intake of alcohol [10].

Patients with hypertriglyceridemia are at a high risk for development of coronary artery disease. If the levels of triglycerides and other risk factors are not controlled, the prognosis is guarded. Only aggressive management of lipids, compliance with life style changes and discontinuation of smoking can improve the outcome. Severe elevations of hypertriglyceridemia can result in acute pancreatitis which can be moderate to severe and even result in multiorgan failure.

In contrast to primary hypertriglyceridemia, there are many secondary causes of hypertriglyceridemia which include the following:

• Alcohol intake can cause marked elevations in plasma VLDL, with or without chylomicronemia. In some alcoholics, plasma triglyceride measurements can be within the normal range because of the body’s ability to increase lipolysis. However, alcohol has the ability to induce impairment in lipolysis, especially if the individual has pre-existing functional deficiency of lipoprotein lipase. This leads to severe elevations in plasma triglycerides.
• Diabetes mellitus
• High carbohydrate diets
• Hypothyroidism over time is known to cause elevations in triglycerides and LDL levels metabolic syndrome
• Nephrotic syndrome
• Nonalcoholic fatty-liver disorder presently affects at least 1/3rd of the American population and its prevalence is increasing due to the epidemic in obesity, insulin resistance and metabolic syndrome. Increased triglyceride and depressed HDL levels are seen in nonalcoholic fatty liver disease [4].
• Obesity
• Pregnancy; During the 3rd trimester of pregnancy, plasma triglyceride levels can rise significantly as a result of compromised lipoprotein lipase activity.
• Renal disease may be associated with elevated LDL-C and in some cases elevated triglycerides. The ongoing uremia impairs lipolysis and is associated with elevated VLDL.
• Medications

• Atypical or second generation antipsychotics

• HAART like protease inhibitors and non-nucleoside reverse transcriptase inhibitors

• Use of high doses of chlorthalidone and thiazide diuretics

• Use of high-doses beta-adrenergic blocking agents that lack intrinsic sympathomimetic activity

• Prolonged use of glucocorticoids

• Oral contraceptives with high estrogen content

• Oral retinoids like isotretinoin

• Tamoxifen

• Unopposed oral estrogen replacement therapy

Other medical conditions
Paraproteinemias (e.g., myeloma, hypergammaglobulinemia in macroglobulinemia, lymphocytic leukemia and lymphoma) and certain autoimmune disorders (e.g.,lupus) can also induce hypertriglyceridemia, which may be due to defective lipolysis as a result of some type of immune-mediated reaction.

Risk factors for heart disease:
• Actively smoking
• Decrease levels of HDL (< 40 mg/dl)
• Men older than 45 and women older than 55
• Family history of premature ischemic heart disease.
• Sudden death or a history of a myocardial infarction in a paternal or male relative before age 55
• Uncontrolled hypertension or present use of antihypertensive medications
If 2 or more risk factors are present, then in the presence of hypertriglyceridemia, more aggressive treatment is needed.

Based on NCEP guidelines which state that levels of triglycerides > 150mg/dl are considered high, the prevalence of hypertriglyceridemia in the USA is about 35% in males and 25% in women. The highest levels are found in Hispanics and Caucasians and somewhat lower levels in African Americans.
Severe hypertriglyceridemia is defined as levels greater than 2,000 mg/dl and this is seen in about 2 patients per 10,000 adults. The numbers are increased in patients with alcoholism or diabetes. The most severe form of hypertriglyceridemia due to lipoprotein lipase deficiency is rare and occurs in 1 person per 1 million individuals.

Hypertriglyceridemia is also common outside the USA. However, the frequency of apoE alleles does vary by racial group. The lower frequencies are found in northern Europeans and the highest frequencies in south East Asians.

Overall hypertriglyceridemia is more common in men than women. In the USA with a rising incidence in childhood obesity and diabetes, there is now emergence of dysbetalipoproteinemia in children.
Levels of triglycerides tend to peak around age 50 and then decline, whereas in women they continue with advancing age. In most cases, the clinical manifestations of apoC-ll deficiency and lipoprotein lipase are observed in childhood.

The two sources of plasma triglycerides are exogenous (dietary) which is transported in chylomicrons, and endogenous which is made in the liver and transported in very low density lipoprotein particles. Once dietary triglycerides enter the small intestine, they are absorbed and secreted in the lymphatic system. These particles travel in the systemic circulation as chylomicrons via the thoracic duct. Some of the triglycerides are removed by the adipose and muscle tissue from the chylomicrons. In the liver, the chylomicrons remnants are taken up and undergo a biochemical conversion into a cholesterol rich lipoprotein. [5] Although the majority of dietary triglyceride found in the systemic circulation is absorbed from the small intestine, a small amount is produced and secreted by the liver.

Lipids synthesized in the liver are then attached to proteins called apolipoproteins that play a role in assembly function and metabolism. Defects in apolipoproteins or the enzymes they interact with it can result in various clinical dyslipidemias. Chylomicron remnants, VLDL, VLDL remnants, and LDL are all atherogenic. When the levels of triglycerides are severe, they can induce acute pancreatitis.

It is not possible to avoid primary hypertriglyceridemia. However, secondary hypertriglyceridemia can be prevented by making changes in lifestyle, eating a low fat diet, exercising regularly and discontinuing smoking. More important, alcohol intake should be decreased or completely discontinued. Once hypertriglyceridemia has been diagnosed, it is vital to follow up with a healthcare provider to ensure that the levels are being lowered with treatment. Maintaining compliance with antihypertensive medications is crucial.

Hypertriglyceridemia is frequently seen alone or in combination with other lipid abnormalities. Hypertriglyceridemia is not a benign clinical feature but is a risk factor for at least 1-4% cases of acute pancreatitis. The risk of acute pancreatitis is highest when the triglyceride levels are > 1,000 mg/dl. Hypertriglyceridemia is never an isolated finding but is frequently associated with other abnormalities such as the metabolic syndrome, low HDL, hypertension and insulin resistance –all features that are associated with ischemic heart disease. With the current global epidemic of obesity there will be a significant increase in the cases of metabolic syndrome. Hence, physicians who encounter hypertriglyceridemia need to be familiar in recognizing and managing this very common disorder.

Presence of elevated triglycerides is found in plasma of many patients but unlike treatment of hypercholesterolemia, the data on treatment of hypertriglyceridemia are less robust. Recent studies on outcomes of cardiovascular disease with patients affected by hypertriglyceridemia reveal a net benefit and reduced risk of dying from heart disease. Even though it is believed that hypertriglycerides are an independent cardiac risk factor, there is no overall consensus on appropriate target levels. In addition, elevated levels of hypertriglyceridemia are also associated with an increased risk of acute pancreatitis. Thus the National Cholesterol Education Program (NCEP) has recommended recording lipid profile in adults over the age of 20. The NCEP guidelines state that when the levels of triglycerides are greater than 150 mg/dl, then a diagnosis of hypertriglyceridemia can be made.

Once hypertriglyceridemia is observed the healthcare provider should search for secondary causes like obesity, high fat diet, smoking, excess alcohol consumption, diabetes, hypothyroidism and use of certain medications. More important these individuals should be evaluated for the metabolic syndrome. Primary hypertriglyceridemia is chiefly due to genetic defects in the apolipoproteins that lead to defective triglyceride metabolism [1] [2] [3].

It is essential to treat hypertriglyceridemia to lower than 500 mg/dl to prevent acute pancreatitis. Furthermore, lowering of triglycerides can also reduce coronary events. How much triglyceride level should be lowered is still a matter of debate. The first treatment for all patients with elevated triglycerides consists of changes in lifestyle, low fat diet, discontinuation of alcohol and smoking, and regular exercise. High doses of omega 3 fatty acids or fish oil supplements can lower triglyceride levels by about 30%. Only when patients do not reach these goals, drug therapy should be initiated. In isolated cases of hypertriglyceridemia, fibrates should be started first. If the patient has coexisting hypercholesterolemia, then one can combine the fibrate with statins.

Classification of triglyceride levels

• Type I is associated with severe elevations in triglycerides and chylomicrons. Hypertriglyceridemia is due to a mutation in the lipoprotein lipase gene, which is critical for the metabolism of chylomicrons and very low-density lipoprotein (VLDL), or the cofactor gene, apolipoprotein (apo) C-II.
• Type IIb is mixed hyperlipidemia (high triglyceride and cholesterol levels), caused chiefly by an increase in VLDL and low-density lipoprotein (LDL).
• Type III goes by several names including broad beta disease or dysbetalipoproteinemia. In this disorder the body is unable to metabolize VLDL, Intermediate lipoprotein (VLDL remnant), and LDL particles and presents a reduced rate of clearance of chylomicron remnants. Patients with dysbetalipoproteinemia have high levels of cholesterol and triglycerides and the disorder is often confused as a Type llb hyperlipidemia. The distinction is that individuals with type lll hyperlipidemia also have marked increases in IDL. Unlike the other hyperlipidemias, type lllb is also responsive to lipid lowering agents.
• Type IV presents with moderate to severe elevations of VLDL. Serum cholesterol is normal and the triglyceride levels are usually less than 1,000mg/dl.
• Type V presents with elevations in VLDL and chylomicrons. Cholesterol levels are high and triglyceride levels are usually > 1,000 mg/dl. The LDL cholesterol level is usually low. This disorder is rare and when a patient has triglyceride levels > 1,000 mg/dl, type V hyperlipidemia should be suspected. These patients often present with acute pancreatitis.

Hypertriglyceridemia is a disorder where the individual has elevated levels of triglycerides in blood. It may coexist with high levels of cholesterol. High levels of triglycerides can induce acute pancreatitis. It is now believed that high levels of triglycerides are also a risk factor for premature heart disease. While some cases of elevated triglycerides are genetically acquired there are some which may be caused by diabetes, obesity, alcohol, smoking, kidney disease and use of certain drugs. It is important to get blood levels of triglycerides measured at least once a year so that they can be treated. The treatment of hypertriglyceridemia can be started with changes in lifestyle, avoiding alcohol, discontinuing smoking and exercise. Drug treatment, instead, is started when lifestyle changes fail to lower the high levels of triglycerides.

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