Mild to moderate elevations in triglyceride levels are now considered a risk factor for heart disease. If the levels are severely elevated, one risks developing acute pancreatitis. Because of the increased risk of premature coronary disease, fibrate therapy is recommended in patients with hypertriglyceridemia. In addition, changes in lifestyle and reduction of risk factors for heart disease can improve prognosis.
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
• Prior diagnosis of hypercholesterolemia
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.
Patients with severe hypertriglyceridemia (>500mg/dl) can also present with:
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.
The NCEP guidelines recommend the following investigations:
To investigate for the metabolic syndrome, the patient should be evaluated for:
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    .
Non pharmacologic treatment
Diet as per NCEP should be:
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.
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.
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.
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 .
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:
• Atypical or second generation antipsychotics
• HAART like protease inhibitors and non-nucleoside reverse transcriptase inhibitors
• Use of high-doses beta-adrenergic blocking agents that lack intrinsic sympathomimetic activity
• Prolonged use of glucocorticoids
• Oral contraceptives with high estrogen content
• 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.  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   .
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
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.